New 2-heteroaryl-substitute benzimidazole derivative

FIELD: chemistry.

SUBSTANCE: invention relates to new bonds in the formula (I-0): or its pharmaceutically acceptable salts, where X represents a carbon atom or nitrogen atom; X1, X2, X3 and X4, each independently, represents a carbon atom or a nitrogen atom; ring A of the formula (II): represents tiazolil, imidazolil, izotiazolil, tiadiazolil, triazolil, oxazolil, oxadiazolil, izoxazolil, pirazinil, piridil, piridazinil, pirazolil or pirimidinil; R¹ represents aryl or represents a 4-10- membered monocyclic or bicyclic heteroring, which has in the ring from 1 to 4 heteroatoms, selected from the group, consisting of a nitrogen atom, sulphur atom and an oxygen atom, and R¹ can be independently substituted with 1-3 R4, and, when the specified heteroring is an aliphatic heteroring, then it can have 1 or 2 double bonds; R² independently represents hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6 alkyl or -(CH2)1-4OH; R3 represents -C1-6 alkyl, -(CH2)1-6-OH, -C(O)-OC1-6 alkyl, -C(O)-OC1-6 alkyl, -(CH2)1-6-NH2, cyano, -C(O)-C1-6 alkyl, halogen, -C2-6 alkenyl, -OC1-6 alkyl, -COOH, -OH or oxo; R4 independently represents -C1-6 alkyl, and the alkyl can be substituted with identical or different 1-3 hydroxyls, halogens, -OC(O)-C1-6 alkyls, and the alkyl can be substituted with 1-3 halogens or -OC1-6 alkyls, -C3-7 cycloalkyl, -C2-6 alkenyl, -C(O)-N(R51)R52, -S(O)2-N(R51)R52,-O-C1-6 alkyl, and C1-6 alkylcan be substituted with a halogen or N(R51)R52, -S(O)0-2-C1-6 alkyl, -C(O)-C1-6 alkyl, and C1-6 alkyl can be substituted with a halogen, amino, CN, hydroxy, -O-C1-6 alkyl, -CH3-aFa, -OC(O)-C1-6 alkyl, -N(C1-6 alkyl)C(O)O-C1-6 alkyl, -NH-C(O)O-C1-6 alkyl, phenyl, -N(R51)R52, -NH-C(O)-C1-6 alkyl, -N(C1-6 alkyl)-C(O)-C1-6 alkyl or -NH-S(O)0-2-C1-6 alkyl, -C(S)-C3-7 cycloalkyl, -C(S)- C1-6 alkyl, -C(O)-O- C1-6 alkyl, -(CH2)0-4-N(R53)-C(O)-R54, -N(R53)-C(O)-O-R54,-C(O)-aryl, it is optional to substitute the halogen, -C(O)-aromatic heteroring, -C(O)-aliphatic heteroring, heteroring, and the heteroring can be substituted with C1-6 alkyl, optionally substituting the halogen or -O-C1-6 alkyl, phenyl, optionally substituting the halogen, -C1-6 alkyl, -O-C1-6 alkyl, halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamidine or nitro; R51 and R52, each independently, represents a hydrogen atom, C1-6 alkyl or a nitrogen atom, R51 and R52 together form 4-7-member heteroring; R53 represents a hydrogen atom or C1-6 alkyl, R54 represents -C1-6 alkyl or alkyls for R53 and R54 and -N-C(O)- together form 4-7-member hydrogen containing heteroring, or alkyls for R53 and R54 and -N-C(O)-O- together form 4-7-member hydrogen containing aliphatic heteroring and an aliphatic heteroring can be substituted with oxo, or an aliphatic heteroring can have 1 or 2 double bonds in the ring; X5 represents -O-, -S-, -S(O)-, -S(O)2-, a single bond or -O-C1-6 alkyl; a independently denotes a whole number 1, 2 or 3; q denotes a whole number from 0 till 2; m denotes a whole number from 0 till 2, except in the case when one of the X5 represents -O-, -S-, -S(O)- or -S(O)2-, and the other from X5 represents a single bond, and R1 represents aryl, optionally substituted with 1-3 R4, or a hydrogen containing aromatic heteroring, consisting of from 1 to 4 heteroatoms, selected from the group, comprising of a hydrogen atom, sulphur atom and an oxygen atom, in the case, when X5, both represent single bonds or in cases, when R1, both represent aliphatic heteroring. The invention also relates to the bonding in the formula (I-12), and also to the bonding in the formula (I-0), to the pharmaceutical composition, to the glucokinase activator and to the medication.

EFFECT: getting new bioactive compounds which can be used for treatment and/or prophylaxis of diabetes or obesity.

23 cl, 603 ex

 

The scope of the invention

This invention relates to a glucokinase activator containing as active ingredient 2-heteroaryl-substituted benzimidazole derivative and applicable in the field of medicine. In addition, it relates to new 2-heteroaryl-substituted benzimidazole derivative.

The level of technology

Glucokinase (GK) (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is one (glucokinase (IV) of the four hexokinase mammals. Glucokinase is an enzyme first stage of glycolysis and catalyzes the reaction of glucose to hexaphosphate glucose. In his expression of glucokinase essentially limited beta cells of the liver and pancreas, and it controls limiting the speed stage of metabolism in these cells, thereby playing an important role in the system of sugar metabolism. Glucokinase in the beta cells of the liver and glucokinase in the beta cells of the pancreas differ from each other by N-terminal 15-amino acid sequence due to differences in splicing between them, but they are identical in enzymatic property. The enzymatic activity of the other three hexokinase (I, II, III), except glucokinase, neutralized with glucose concentrations at most 1 mm, but the Km of glucokinase to glucose equal to 8 mm and is close to the physiological level of nigerianischer in the blood. Therefore, in accordance with the change in the level of blood sugar from the normal level of blood glucose (5 mm) to an elevated level of blood sugar after a meal (10-15 mm) extracellular glucose metabolism accelerated by glucokinase.

Ten years ago it was hypothesized that the glucokinase can act as sensitive to glucose agent in the beta cells of the pancreas and liver [for example, see D. Garfinkel et al., Computer modeling identifies glucokinase as glucose sensor of pancreatic beta-cell; American Journal discrimination, Vol.247 (3Pt2), 1984, pp.527-536].

The results of modern research with glucokinase gene in mice confirm that the activity of glucokinase plays an important role in systemic glucose homeostasis. Mice in which the gene for glucokinase was destroyed, died shortly after birth [for example, see Grupe A. et al., Transgenic knockouts reveal a critical requirement for pancreatic beta-cell glucokinase in maintaining glucose homeostasis, Cell, Vol.83, 1995, pp.69-78]; but, on the other hand, normal or diabetic mice, in which glucokinase excessively expressed, have low sugar level in blood [for example, see T. Ferre et al., Correction of diabetic alterations by glucokinase; Proceedings of the National Academy of Sciences of the U.S.A. Vol.93, 1996, pp.7225-7230].

With the increase in their concentrations of glucose, the reaction of the beta cells of the pancreas and the response of liver cells, although different from each other, both n is focused on reducing the level of blood sugar. Beta cells of the pancreas begins to secrete more insulin and the liver takes sugar is deposited in the form of glycogen, and simultaneously reduces the release of sugar.

In this sense, the change of the enzymatic activity of glucokinase plays an important role in glucose homeostasis mammals by beta cells of the liver and pancreas. In the case of juvenile diabetes, which is referred to as MODY2 (diabetes in young adults), discovered the gene mutation of glucokinase, and reduced glucokinase causes an increase in sugar content in the blood (for example, see Vionnet N. et al., Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus; Nature Genetics, Vol.356, 1992, pp.721-722).

On the other hand, detected pedigree mutation increased glucokinase, and representatives of family lines show the symptoms of low blood sugar (for example, see B. Glaser et al., Familial hyperinsulinism, caused by an activating glucokinase mutation; New Endland Journal of Medicine, Vol.338, 1998, pp.226-230).

On this basis, glucokinase acts as sensitive to glucose agent and plays an important role in glucose homeostasis in humans. On the other hand, the control of sugar level in the blood using glucokinase sensor systems may be possible in many patients with diabetes type II. Activating glucokinase substance presumably m who may be promoting the secretion of insulin action in the beta cells of the pancreas and accelerating the absorption of sugar and inhibiting the release of sugar in the liver, therefore, it can be used as medicines for patients with diabetes type II.

Recently found that glucokinase type beta cells of the pancreas limited expressed locally in the rat brain, especially in his ventromedial hypothalamus (VMH). About 20% of all neurocytol in the VMH are considered sensitive to glucose neurons, and therefore it is considered that they can play an important role in the regulation of body weight. When glucose is administered to the brain of the rat, then it reduces the amount of food consumed, but when glucose metabolism is slow intracerebrally the introduction of glucosamine, an analogue of glucose, then it calls hyperphagia. From the electrophysiological experiment Pets that are sensitive to glucose neurons are activated in accordance with the physiological changes of glucose concentration (from 5 to 20 mm), but when glucose metabolism is inhibited by glucosamine or the like, then their activity is retarded. In sensitive to the concentration of glucose system in VMH assumes mediated glucose mechanism similar to the secretion of insulin in the beta cells of the pancreas. Therefore, it may be possible that the substance to activate glucokinase in the VMH, in addition to the beta cells of the liver and pancreas, might be effective is e only for the correction of the level of blood sugar, but also to solve obesity, which is typical of many patients with type II diabetes.

From the above description it follows that the compound having the effect of activating glucokinase, applicable to drug and/or prophylactic agents against diabetes and/or drug and/or prophylactic agents against chronic complications of diabetes such as retinopathy, nephropathy, neurosis, ischemic cardiopathy, arteriosclerosis, and even for medicinal and/or prophylactic agents against obesity.

As for benzimidazole derivatives described, for example, a compound of the following formula (for example, see JP-A 2000-026430):

The connection of the mentioned formula is a substituent in position 2 of the structure of benzimidazole, but the Deputy is 4-chlorophenyl, and it differs from the ring in this invention.

In addition, the article discusses the use of the compounds as inhibitors of the production of interleukin and not given any description, showing that the connection can be applicable to drug and/or prophylactic agents against diabetes or description implying it.

About benzimidazole compounds, for example, describes a compound of the following formula (for example, see WO 2004017963):

With the unity of the specified formula has only one substituent in the benzene ring structure of benzimidazole, and, although it has the substituent in position 2 of the structure of benzimidazole, the Deputy is a 5-chloranil, and it differs from the ring in this invention.

In addition, the article discusses the use of the compounds as inhibitors of factor XA and factor VIIa and not given any description, showing that the connection can be applicable to drug and/or prophylactic agents against diabetes or description implying it.

The invention

Problems that the invention must solve

The purpose of this invention to provide a new 2-heteroaryl-substituted imidazole derivative and a glucokinase activator containing it, especially providing drug and/or prophylactic agent against diabetes and obesity.

Conducted thorough research on the development of new drugs against diabetes, which has pharmaceutical efficiency, exceeding the efficiency of these existing medications for diabetes, thanks to his effect, different from the effect of existing drugs, and which has the additional pharmaceutical effectiveness, and as a result found that the new 2-heteroaryl-substituted benzimidazole derivative is activating glucokinase effect, and the invention is completed.

Conques is to maintain the invention relates to (1) to the compound of formula (I-0):

where:

X represents a carbon atom or a nitrogen atom;

X1X2X3and X4each independently represent a carbon atom or a nitrogen atom;

ring A represents A 5 - or 6-membered nitrogen-containing aromatic heterokonta formula (II), optionally having in the ring 1 to 3 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, but excluding the nitrogen atom N* in formula II:

or is the double ring of the nitrogen-containing aromatic heterokonta condensed with a phenyl or pyridium;

R1represents aryl or represents a 4 to 10-membered monocyclic or dual circular heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and R1may be independently substituted by 1-3 R4and when heteroclita is aliphatic heterokonta, then it can have 1 or 2 double bonds;

R2independently represents hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6alkyl or -(CH2)1-4OH;

R3represents-C1-6alkyl, -(CH2)1-6-OH, -C(O)-OC1-6alkyl, -(CH2)1-6-OC1-6alkyl, -(CH2)1-6 -NH2, cyano, -C(O)-C1-6alkyl, halogen, -C2-6alkenyl, -OC1-6alkyl, -COOH, -OH or oxo;

R4independently represents-C1-6alkyl, optionally substituted, the same or different, 1 to 3 hydroxyl, halogen, -OC(O)-C1-6alkilani, optionally substituted by 1-3 Halogens, or-OC1-6alkilani,

-C3-7cycloalkyl,

-C2-6alkenyl,

-C(O)-N(R51R52,

-S(O)2-N(R51R52,

-O-C1-6alkyl, optionally substituted with halogen, or N(R51R52,

-S(O)0-2-C1-6alkyl,

-C(O)-C1-6alkyl, optionally substituted with halogen, amino, CN, hydroxy, -O-C1-6by alkyl, -CH3-aFa, -OC(O)-C1-6by alkyl, -N(C1-6alkyl)C(O)O-C1-6by alkyl, -NH-C(O)O-C1-6the alkyl, phenyl, -N(R51R52, -NH-C(O)-C1-6by alkyl, -N(C1-6alkyl)-C(O)- C1-6the alkyl or-NH-S(O)0-2-C1-6by alkyl),

-C(S)-C3-7cycloalkyl,

-C(S)-C1-6alkyl,

-C(O)-O-C1-6alkyl,

-(CH2)0-4-N(R53)-C(O)-R54,

-N(R53)-C(O)-O-R54,

-C(O)-aryl, optionally substituted with halogen,

-C(O)-aromatic heterokonta,

-C(O)-aliphatic heterokonta,

heterokonta, optionally substituted C1-6the alkyl (C1-6the alkyl may be substituted with halogen or-O-C1-6by alkyl),

the dryer is l, optionally substituted with halogen, -C1-6by alkyl, -O-C1-6the alkyl,

halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamino or nitro;

R51and R52each independently represent a hydrogen atom, a C1-6alkyl or a nitrogen atom, R51and R52together form a 4-7-membered heterokonta;

R53represents a hydrogen atom or a C1-6alkyl,

R54represents C1-6alkyl, or

alkali for R53and R54and-N-C(O)- together form a 4-7-membered nitrogen-containing aliphatic heterokonta, or

alkali for R53and R54and-N-C(O)-O - together form a 4-7-membered nitrogen-containing aliphatic heterokonta, and aliphatic heterokonta may be substituted by oxo, or aliphatic heterokonta may have 1 or 2 double bonds in the ring;

X5represents-O-, -S-, -S(O)-, -S(O)2-, a single bond or-O-C1-6alkyl;

a independently denotes an integer of 1, 2 or 3;

q denotes an integer from 0 to 2;

m means an integer from 0 to 2, but excluding the case when one of X5represents-O-, -S-, -S(O)- or-S(O)2-and the other of X5represents a single bond, and R1represents aryl or nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and the reel may be substituted by 1-3 R 4the case when X5both represent a single bond, or the case when R1both represent an aliphatic heterokonta, or its pharmaceutically acceptable salt.

The invention also relates to the following items:

(2) the Compound or pharmaceutically acceptable salt p.(1)where in the formula (I-0) X1- X4are all carbon atoms, and

(3) the Compound or pharmaceutically acceptable salt according to claim 1, where in formula (I-0) X5represents-O-, -S-, -S(O)-, -S(O)2- or a single bond.

The invention also relates to the following items:

(4) the Compound or pharmaceutically acceptable salt according to claim 1, where the compound of formula (I-0) represented by formula (I-1):

where:

R11represents phenyl, optionally substituted by 1-3 R4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4; and X51represents-O-, -S-, -S(O)- or-S(O)2-; and other symbols have the above values.

The invention also relates to the following items:

(5) the Compound or pharmaceutically acceptable salt according to claim 4, where in the formula (I-1) R11both represent Emily, optionally substituted by 1-3 R4;

(6) the Compound or pharmaceutically acceptable salt according to claim 4, where in the formula (I-1) R11both are 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4and

(7) the Compound or pharmaceutically acceptable salt according to claim 4, where in the formula (I-1) one of R11means phenyl, optionally substituted by 1-3 R4and the other of R11represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4.

The invention also relates to the following items:

(8) the Compound or pharmaceutically acceptable salt of formula (I-0), which is represented by formula (I-2):

where:

R11represents phenyl, optionally substituted by 1-3 R4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic Goethe o-ring must may be substituted by 1-3 R 4and

R12represents a 4-7-membered nitrogen-containing heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and

R12may be substituted by 1-3 R4and when heteroclita is aliphatic heterokonta, then it can have 1 or 2 double bonds;

X51represents-O-, -S-, -S(O)- or-S(O)2-;

X52represents-O-, -S-, -S(O)-, -S(O)2- or a single bond; and other symbols have the above values.

The invention also relates to the following items:

(9) the Compound or pharmaceutically acceptable salt of claim 8, where in the formula (I-2) R12represents a 4-7-membered saturated nitrogen-containing aliphatic heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and a nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4and X52represents a single bond; or R12is a 5-7 membered nitrogen-containing aliphatic, heterokonts is, having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds, and 5 - to 7-membered heterokonta may be substituted by 1-3 R4and X52represents-O-, -S-, -S(O)- or-S(O)2-;

(10) the Compound or pharmaceutically acceptable salt of claim 8, where in the formula (I-2) R12represents a 4-7-membered saturated nitrogen-containing aliphatic heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and a nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4and X52represents a single bond;

(11) the Compound or pharmaceutically acceptable salt of claim 8, where in the formula (I-2) R12is a 5-7 membered nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and atom color is Yes, and having in the ring 1 or 2 double bonds, and a 5-7 membered heterokonta may be substituted by 1-3 R4and X52represents-O-, -S-, -S(O)- or-S(O)2-and

(12) the Compound or pharmaceutically acceptable salt of claim 8, where in the formula (I-2)

R12is a 5-7 membered nitrogen-containing aliphatic heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds, and nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4and X52means-O-.

The invention also relates to the following items:

(13) the Compound or pharmaceutically acceptable salt of formula (I-1), which is represented by formula (I-11):

where:

the symbols have the above meanings;

(14) the Compound or pharmaceutically acceptable salt of formula (13), which are represented by the formula (I-12), where X51both represent-O-;

(15) the Compound or pharmaceutically acceptable salt of formula (I-1), which is represented by formula (I-12):

where:

the symbols have the above values, and

(16) the Compound or pharmaceutical is acceptable salt according to clause 15, where in the formula (I-12) X51both represent-O-.

The invention also relates to the following items:

(17) the Compound or pharmaceutically acceptable salt of claim 10, where in the formula (I-2) R12represented by formula (III-1):

or the formula (III-2):

where n means an integer from 1 to 3; R41has the same meanings as R4.

The invention also relates to the following:

(18) the Compound or pharmaceutically acceptable salt according to any one of claims 1 to 17, where the ring A represents thiazolyl, imidazolyl, isothiazolin, thiadiazolyl, oxadiazolyl, triazolyl, oxazolyl, isoxazolyl, pyrazinyl, pyridyl, pyridazinyl, pyrazolyl or pyrimidinyl, which can be substituted by 1-3 R4.

The invention also relates to the following:

(19) the Compound of the formula (I-0), which is the following connection:

5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-(methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazo is,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-(1-methyl-1H-pyrazole-3-yl)-1H-benzimidazole,

5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-(1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,3-debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,4-debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,5-debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-herperidin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-herperidin-3-yloxy)-6-(6-econsultancy pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-chloropyridin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-chloropyridin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-canopied the n-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole,

5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-(tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-deformationen-3-yloxy)-6-(3-chloro-4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-fluoro-phenoxy)-2-(pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,6-di is Thor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-(1H-pyrazole-3-yl)-1H-benzimidazole,

4-(2-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,3-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,5-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(2-(6-(5-bromo-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-hydroxymethyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-H-benzimidazole-5-yl)pyrrolidin-1-carboxamid,

2-hydroxy-1-(2-(6-(4-methanesulfonyl-1 phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

2-fluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-methylamino-Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

N-(5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-yl)acetamide", she

1-(2-(2-(5-bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

N-(2-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)acetamide", she

6-(1-acetylpyrrolidine-2-yl)-5-(4-(methoxymethyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole monotropaceae,

1-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)pyridin-2(1H)-he,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

(2-(2-(5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl)methylamine,

6-(1-acetylpyrrolidine-2-yl)-5-((6-([1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(1-acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(1-acetyl-5-methylpyrrolidine-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-methoxypyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl,

2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxamid,

5'-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it,

3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it,

6-(1-acetylpyrrolidine-2-yl)-5-((6-methylpyridin-3-yl)oxy)-2-p is ridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-pyrazin-2-espiridion-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetyl-3-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it,

6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-5-((6-pyrazin-2-espiridion-3-yl)oxy)-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)Etalon,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(5-methyl-[1,2,4]-oxadiazol-3-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

6-(1-acetyl-5-methylpyrrolidine-2-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

N-methyl-2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxetanone,

6-(1-acetyl-5-methylpyrrolidine-2-yl)-5-((6-(methoxymethyl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon,

1-(1-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon,

1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon or

1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-gasoline idazole-5-yl)-4-fluoro-pyrrolidin-2-yl)alanon or their pharmaceutically acceptable salts.

The invention also relates to the following:

(20) a pharmaceutical composition containing the following components (1)to(3), which is used for the treatment, prevention and/or delay of type II diabetes:

(1) the compound according to any one of claims 1 to 19,

(2) one or more compounds selected from the following groups (a)-(h):

(a) any other activator of glucokinase,

(b) bis-guanin,

(c) a PPAR agonist,

(d) somatostatin,

(e) inhibitor α-glucosidase,

(f) insulin and

(g) an inhibitor of DPP-IV (dipeptidyl peptidases IV)

(3) a pharmaceutically acceptable carrier;

(21) a glucokinase Activator containing a compound or its pharmaceutically acceptable salt according to any one of claims 1 to 19 as its active ingredient;

(22) the Medicinal product for the treatment and/or prevention of diabetes, containing the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 20 as its active ingredient, and

(23) Drug and/or prophylactic agent against obesity, containing the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 20 as its active ingredient.

The best course of action for carrying out the invention

The meaning of the terms used in the description below, and the compounds according to the invention is described in more detail hereafter.

If otherwise, concr the IDT is not specified in this description, the following groups have the meanings given below.

"Aryl" means preferably aromatic hydrocarbon ring having 6 to 14 carbon atoms, including, for example, phenyl, naphthyl, biphenyl, antril. Of them, preferred phenyl and naphthyl; and more preferred is phenyl.

"C1-6alkyl" means a linear or branched alkyl having from 1 to 6 carbon atoms, including, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, neopentyl, isopentyl, 1,1-dimethylpropyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,2,2-trimethylpropyl, 1-ethyl-2-methylpropyl.

"C2-6alkenyl" means a linear or branched alkenyl having from 2 to 6 carbon atoms, including, for example, allyl, 2-propenyl, 1-butenyl, 2-butenyl, 2-methyl-2-butenyl, 1-pentenyl.

"C3-7cycloalkyl" specifically includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl.

"Halogen" means fluorine, chlorine, bromine or iodine.

"-(CH2)1-6-OH" includes, for example, hydroxymethylene, hydroxyethylene.

"-O-C1-6alkyl" includes, for example, methoxy, ethoxy, propoxy or tert-is ataxi.

"-(CH2)1-6-OC1-6alkyl" includes, for example, methoxymethyl, methoxyethyl, propylacetate, isopropylaminomethyl.

"-C(O)-C1-6alkyl" includes, for example, acetyl, ethylcarboxyl, isopropylcarbonate, propylmalonic.

"-C(O)OC1-6alkyl" includes, for example, methoxycarbonyl, etoxycarbonyl or tert-butoxycarbonyl.

"-(CH2)1-6-NH2includes, for example, aminomethyl, aminoethyl, aminopropyl.

"-NH-C1-6alkyl" includes, for example, methylamino, ethylamino, propylamino or 2-methylbutyl-amino.

"N-di(C1-6alkyl)" means a group of the same or different aforementioned "C1-6Akilov", combined with N, and includes, for example, dimethylamino, ethylpropylamine, 2-methylbutyl-1-methylamino. In-N-di-(C1-6the alkyl)", equal or different With1-4alkali may form a ring together with a nitrogen atom. Examples of rings include piperidine, pyrrolidine.

"-CH3-aFa" means a group derived from methyl substitution from 1 to 3 hydrogen atoms therein fluorine atoms, and includes, for example, trifluoromethyl, deformity or vermeil.

"-OCH3-aFa" means a group specified for "-CH3-aFa"combined with an oxygen atom, and includes, for example, triptoreline, deformedarse or formatosi.

a denotes an integer from 1 to 3.

For more konkretnej the disclosure compounds according to the invention the symbols, used in formulas (I-0), (I-1), (I-2), (I-11) or (I-12), described with reference to specific examples.

The compounds of formula (I-0) according to the invention is described.

X5represents-O-, -S-, -S(O)-, -S(O)2-, a single bond or-O-C1-6alkyl.

R1represents aryl or represents a 4 to 10-membered monocyclic or bicyclic heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

"Aryl" for R1may be the same as the above aryl, preferably phenyl, naphthyl or biphenyl, preferably phenyl.

"4-7-membered monocyclic or 9 - or 10-membered condensed heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom"represented by R1means 4-7-membered monocyclic or 9 - or 10-membered bicyclic aliphatic heterokonta or aromatic heterokonta as a single ring in which from 1 to 4 constituting the ring atoms heterokonta are heteroatoms selected from nitrogen atom, sulfur atom and oxygen atom and other atoms of the components heterokonta atoms are carbon atoms.

When heterokonta has a nitrogen atom in the ring, then the nitrogen atom can image is the close co N-oxide.

When heterokonta has 2 or 3 heteroatoms in the ring, then the heteroatoms may be the same or different.

When heteroclita is aliphatic heterokonta, then it can have 1 or 2 double bonds in the ring.

When heteroclita is aliphatic heterokonta, then the methylene in heteroclite may be substituted by a nitrogen atom, a sulfur atom or an oxygen atom, and optionally a sulfur atom may be oxidized to sulfinyl or sulfonyl.

Heterokonta includes, for example, azetidine, diazolidinyl, pyrrolidinyl, pyrrolidinyl, 2-pyrrolidinyl, azepane, 2.5-dioxopyrimidine, 2-benzoxazinones, 1,1-dioxotetrahydrofuran, 2,4-dioxoimidazolidin, 2-oxo-[1,3,4]-(4-triazolyl), 2-oxazolidinone, 5,6-dihydrouracil, 1,3-benzodioxolyl, [1,2,4]-oxadiazolyl, 2-azabicyclo[2,2,1]heptyl, 4-thiazolidone, morpholinyl, 2-oxitetraciclina, tetrahydrofuranyl, 2,3-dihydrobenzofuranyl, benzothiazyl, isoxazolyl, tetrahydropyranyl, piperidyl, 1-oxo-1,3-dihydroisoquinolyl, piperazinil, thiomorpholine, 1,1-dioxothiazolidine, tetrahydropyranyl, 1,3-DIOXOLANYL, homopiperazine, thienyl, isoxazolyl, imidazolyl, pyrrolyl, thiazolyl, thiadiazolyl, isothiazolin, [1,2,4]-triazolyl, [1,2,3]-triazolyl, pyranyl, indolyl, pyrimidinyl, thiazolyl, pyrazinyl, pyridazinyl, pyridyl, 4-pyridinyl, x is nail or ethanolic.

Of them, 4-7-membered monocyclic heterokonta specifically includes, for example, azetidine, isoxazolyl, pyrrolidinyl, 2-pyrrolidinyl, 2,5-dioxopiperazinyl, morpholino, tetrahydrofuranyl, azepane, piperidyl, piperazinil, thiomorpholine, tetrahydropyranyl, imidazolyl, triazolyl, oxadiazolyl, tetrazolyl, pyrazolyl, indolyl, thiazolyl, thiadiazolyl, pyrazinyl, pyridazinyl or pyridyl.

Of them, 4-7-membered monocyclic aliphatic heterokonta specifically includes, for example, azetidine, pyrrolidine, piperidine, piperidinyl, azepane, piperazinil, morpholino, thiomorpholine, homopiperazine, imidazolidinyl, pyrazolidine.

Of them 5 - or 6-membered monocyclic aromatic heterokonta specifically includes, for example, pyrrolyl, furyl, thienyl, pyrazolyl, isoxazolyl, isothiazolin, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl.

9 - or 10-membered condensed heterokonta specifically includes, for example, benzofuranyl, benzimidazolyl, benzothiophene, benzothiazole, benzisothiazole, benzoxazole, benzisoxazole, predominately, hinely, ethanolic, honokalani, hintline, phthalazine, cinnoline, indolyl, indazoles, purinol, indolizinyl, isoindolyl, pteridinyl or naphthyridine.

Heterokontophyta preferably 4-7-membered monocyclic aliphatic heterokonta or 5 - or 6-membered aromatic heterokonta, in which at least one of the components heterokonta atoms is a nitrogen atom.

R1may be substituted by 1-3 R4.

R4independently represents-C1-6alkyl (the alkyl may be substituted, the same or different, 1 to 3 hydroxyl, halogen, -OC(O)-C1-6alkilani (the alkyl may be substituted by 1 to 3 Halogens), or-OC1-6alkilani),

-C3-8cycloalkyl,

-C2-6alkenyl,

-C(O)-N(R51R52,

-S(Oh)2-N(R51R52,

-O-C1-6alkyl (C1-6the alkyl may be substituted with halogen or N(R51R52),

-S(Oh)0-2-C1-6alkyl,

-C(O)-C1-6alkyl (C1-6the alkyl may be substituted with halogen, amino, CN, hydroxy, -O-C1-6by alkyl, -CH3-aFa, -OC(O)-C1-6by alkyl, -N(C1-6alkyl)C(O)O-C1-6the alkyl, phenyl, -N(R51R52, -NH-C(O)-C1-6by alkyl, -N(C1-6alkyl)-C(O)-C1-6the alkyl or-NH-S(O)0-2-C1-6by alkyl),

-C(O)-C3-8cycloalkyl,

-C(S)-C1-6alkyl,

-C(O)-O-C1-6alkyl,

-(CH2)0-4-N(R53)-C(O)-R54,

-N(R53)-C(O)-O-R54,

-C(O)-aryl (the aryl may be substituted with halogen),

-C(O)-aromatic heterokonta,

-C(O)-aliphatic heterokonta,

heterokonta (heterokonta may be replaced by-C1-6the alkyl (C1-6alkyl can b shall be substituted with halogen or-O-C 1-6by alkyl)),

phenyl, (phenyl may be substituted with halogen, -C1-6by alkyl, -O-C1-6by alkyl),

halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamino or nitro;

"Halogen" for R4has the above values.

"-C1-6alkyl for R4means a linear or branched alkyl having from 1 to 6 carbon atoms, including, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, neopentyl, isopentyl, 1,1-dimethylpropyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,2,2-trimethylpropyl, 1-ethyl-2-methylpropyl.

"-C1-6the alkyl may be substituted by 1-3 hydroxyl, halogen, -OC(O)-C1-6alkilani (the alkyl may be substituted by 1 to 3 Halogens), or-O-C1-6alkilani.

In the case where the "-C1-6alkyl has 2 or 3 of these substituents, they may be the same or different.

The halogen for the substituent includes the above halogen-free.

-OC(O)-C1-6the alkyl for the substituent includes, for example, methylcarbonate, ethylcarbonate, isopropylcarbonate.

-OC(O)-C1-6the for alkyl substituent may be substituted by 1-3 these atoms is Loginov.

-O-C1-6the alkyl for the substituent includes, for example, methoxy, ethoxy, propoxy, isopropoxy.

"-S(O)0-2-C1-6alkyl for R4means the group-S(O)0-2-combined with the specified-C1-6the alkyl, including, for example, -S-ethyl-S-methyl-S-isopropyl, -S,-propyl, -S(O)2-methyl, -S(O)2-ethyl.

-C1-6alkyl in "-S(O)0-2-C1-6the alkyl may be substituted by hydroxy.

"-C3-8cycloalkyl for R4includes the above group.

"-C2-6alkenyl for R4includes the above group.

"C(O)N(R51R52for R4means substituted or unsubstituted carbamoyl means or 4-7-membered aliphatic heterokonta formed jointly N, R51and R52and combined with the carbonyl.

From "C(O)N(R51R52for R4substituted or unsubstituted carbarnoyl includes, for example, carbarnoyl, methylcarbamoyl, ethylcarbitol, isopropylcarbamate, propellerblades, ethylmethylamino, dimethylcarbamoyl, isopropylaminocarbonyl, diisopropylamino, diethylcarbamoyl.

From "C(O)N(R51R52for R44-7-membered aliphatic heterokonta formed jointly N, R51R52specifically includes, for example, azetidine, pyrrolidine, piperidine, piperazinil, morpholino. Accordingly, C(O)N(R5IR52includes AZ is tidin-1-carbonyl, pyrrolidin-1-carbonyl, piperidine-1-carbonyl, piperazine-1-carbonyl, morpholine-1-carbonyl.

"-C(O)-O-C1-6alkyl for R4may be the same as the above "-C(O)-O-C1-6alkyl".

"-O-C1-6alkyl for R4may be the same as the above "-O-C1-6alkyl".

-O-C1-6the alkyl may be substituted with halogen or N(R51R52.

"-C(O)-C1-6alkyl for R4may be the same as the above "-C(O)-C1-6alkyl".

"-C(O)-C1-6the alkyl may be substituted with halogen, amino, -CH3-aFa, CN, hydroxy, -O-C1-6by alkyl, -O-C(O)-C1-6by alkyl, -N(C1-6alkyl)-C(O)O-C1-6by alkyl, -NH-C(O)O-C1-6the alkyl, phenyl, -N(R51R52, -NH-C(O)-C1-6by alkyl, -N(C1-6alkyl)-C(O)-C1-6the alkyl or-NH-S(O)0-2-C1-6the alkyl.

"Halogen" for the substituent may be the same as the above halogen.

"-CH3-aFa" for the substituent may be the same as the above "-CH3-aFa".

"-O-C1-6alkyl" for the substituent may be the same as the above "-O-C1-6alkyl".

"-O-C(O)-C1-6alkyl" for the substituent may be the same as the above "-O-C(O)-C1-6alkyl".

"-N-(C1-6alkyl)-C(O)O-C1-6alkyl" for the substituent represents a group-N-(C1-6alkyl)-, which combined with the specified-C(O)O-C1-6 the alkyl, and specifically includes, for example, -N(Me)-C(O)O-tert-butyl.

"-NH-C(O)O-C1-6alkyl" for the substituent means a group of-NH-, which combined with the specified-C(O)O-C1-6the alkyl, and specifically includes-NH-C(O)O-methyl, -NH-C(O)O-ethyl, -NH-C(O)O-isopropyl, -NH-C(O)-propyl.

"-N(R51R52" for Deputy may have the same values as above for "-N(R51R52".

"-NH-C(O)-C1-6alkyl" for the substituent means a group-NH-C(O)-, which combined with the specified-C1-6the alkyl, and specifically includes, for example, -NH-C(O)-methyl, -NH-C(O)-ethyl, -NH-C(O)-isopropyl, -NH-C(O)-propyl.

"-N-(C1-6alkyl)-C(O)-C1-6alkyl" for the substituent means a group-N-(C1-6alkyl)-C(O)-, which combined with the specified-C1-6the alkyl, and specifically includes, for example, -N(methyl)-C(O)-methyl, -N(methyl)-C(O)-ethyl, -N(ethyl)-C(O)-isopropyl, -N(methyl)-C(O)-isopropyl, -N(isopropyl)-C(O)-methyl.

-NH-S(O)0-2-C1-6the alkyl for the substituent means a group of-NH-, which combined with the specified-S(O)0-2-C1-6the alkyl and specifically includes, for example, -NH-S(O)2-methyl, -NH-S(O)2-ethyl, -NH-S(O)2is isopropyl.

"-C(O)-C1-6alkyl", not necessarily having the above Deputy C1-6the alkyl specifically includes, for example, formational, 2,2,2-triptoreline, cyanomethylene, hydroxymethyluracil, 2-hydrooximethylcarbamil, marks nietykalni, aminomethylpropanol, N-methylaminoethanol, 2-phenylethylamine.

"-C(S)-C1-6alkyl for R4means the group-C(S)-that combined with the specified "-C1-6the alkyl and specifically includes, for example, -C(S)-methyl, -C(S)-ethyl, -C(S)-isopropyl, -C(S)-propyl.

In "-(CH2)0-4-N(R53)-C(O)-R54for R4R53means a hydrogen atom or-C1-6alkyl, and R54means-C1-6alkyl, or-N(R53)-C(O)-R54in "-(CH2)0-4-N(R53)-C(O)-R54" -N-C(O)- and R53and R54may together form a 4-7-membered nitrogen-containing aliphatic heterokonta (heterokonta may be substituted by oxo, and may have 1 or 2 double bonds in the ring).

"-(CH2)0-4-N(R53)-C(O)-R54"where R53represents a hydrogen atom or-C1-6alkyl, and R54represents-C1-6alkyl specifically includes, for example, -CH2-NH-C(O)-methyl, -CH2-NH-C(O)-ethyl, -CH2-NH-C(O)-isopropyl, -CH2-NH-C(O)-propyl, -CH2-N(methyl)-C(O)-methyl, -CH2-N(ethyl)-C(O)-methyl, -NH-C(O)-methyl, -NH-C(O)-ethyl, -NH-C(O)-isopropyl, -NH-C(O)-propyl, -N(methyl)-C(O)-methyl, -N(ethyl)-C(O)-methyl.

In the case where a-N-C(O)- and C1-6-alkili for R53and R54together form a 4-7-membered nitrogen-containing aliphatic heterokonta (heterokonta may be substituted by oxo, and may have 1 or 2 double bonds in the ring), "-(CH2)0- -N(R53)-C(O)-R54" specifically includes, for example, groups of the following formula (IV):

In "-N(R55)-C(O)-O-R56for R4R55represents a hydrogen atom or-C1-6alkyl, and R56represents-C1-6alkyl, or-N(R55)-C(O)-O-R56in "-N(R55)-C(O)-O-R56" -N-C(O)-O - and alkali for R55and R56together form a 4-7-membered nitrogen-containing aliphatic heterokonta.

In the case where R55represents a hydrogen atom or-C1-6alkyl, and R56represents-C1-6alkyl, "-N(R55)-C(O)-O-R56" specifically includes, for example, -NH-C(O)-O-methyl, -NH-C(O)-O-ethyl, -NH-C(O)-O-isopropyl, -NH-C(O)-O-propyl, -N(methyl)-C(O)-O-methyl, -N(ethyl)-C(O)-O-methyl.

In the case where a-N-C(O)-O - and C1-6alkali for R55and R56together form a 4-7-membered nitrogen-containing aliphatic heterokonta, "-N(R53)-C(O)-R54" specifically includes, for example, groups of the following formula (V):

"-C(O)-aryl" for R4means the group of carbonyl, which is combined with the specified aryl and specifically includes, for example, benzoyl, afterburner.

Aryl "-C(O)-aryl may be substituted by 1-3 above halogen atoms.

When the group has 2 or 3 halogen atom for deputies, then they may be the same or different.

"-C(O)-Aro is eticheskoe heterokonta for R 4means the group of carbonyl, which is combined with the specified 5 - or 6-membered monocyclic aromatic heterokonta or 9 - or 10-membered bicyclic aromatic heterokonta and specifically includes, for example, -C(O)pyrrolyl, -C(O)-furyl, -C(O)-thienyl, -C(O)-, -C(O)pyrazolyl, -C(O)-isoxazolyl, -C(O)-isothiazolin, -C(O)-imidazolyl, -C(O)-oxazolyl, -C(O)-thiazolyl, -C(O)-triazolyl, -C(O)-oxadiazolyl, -C(O)-thiadiazolyl, -C(O)-tetrazolyl, -C(O)pyridyl, -C(O)pyrazinyl, -C(O)pyrimidinyl, -C(O)pyridazinyl.

"-C(O)-aromatic heterokonta for R4means the group of carbonyl, which is combined with the specified 4-7-membered monocyclic aliphatic heterokonta and specifically includes, for example, -C(O)-azetidinol, -C(O)pyrrolidinyl, -C(O)-piperidine, -C(O)-piperidinyl, -C(O)-azepane, -C(O)-piperazinil, -C(O)-morpholino, -C(O)-thiomorpholine, -C(O)-homopiperazine, -C(O)-imidazolidinyl, -C(O)-pyrazolidine.

"Heterokonta for R4may be the same as "heterokonta for R1.

Heterokonta may be substituted by 1-3-C1-6alkilani, halogen or-O-C1-6alkilani.

In the case where the ring is substituted by 2 or 3 such substituents, they may be the same or different.

-C1-6alkyl, halogen and-O-C1-6the for alkyl substituents can be the same as specified for the group.

"Halogen" for R4may be the same, ka is the above "halogen".

"Phenyl" for R4may be substituted with halogen, -C1-6the alkyl or-O-C1-6the alkyl.

In the case where R1it has 2 or 3 R4then , the same or different two R4may together form a 4-6-membered ring, which specifically includes, for example, groups of the following formula (VI):

-X5- represents-O-, -S-, -S(O)-, -S(O)2-, a single bond or-O-C1-6alkyl.

Preferably X5- represents-O-, -S-, -S(O)-, -S(O)2- or a single bond.

R1-X5- (R1may be substituted by 1-3 R4) concretely includes, for example, phenylsulfonyl, phenoxy, benzyloxy, penetrate, 2-cianfrocca, 3 cianfrocca, 4-cianfrocca, 2-cyano-6-fervency, 2-carbamoylphenoxy, 3 carbamoylphenoxy, 4-carbamoylphenoxy, 2-fluoro-6-carbamoylphenoxy, 2-methylcarbamoylmethyl, 3 methylcarbamate, 4-methylcarbamoylmethyl, 2-dimethylcarbamate, 3 dimethylcarbonate, 4-dimethylcarbamate, 2-methoxy-phenoxy, 3 methoxyphenoxy, 4-methoxyphenoxy, 4-methoxymethylethoxy, 2-isopropylphenoxy, 3 isopropylphenoxy, 4-isopropylphenoxy-2-methylphenoxy, 3 methylphenoxy, 4-methylphenoxy, 2-ethylenoxy, 3 ethylenoxy, 4-ethylenoxy, 2-acetylphenol, 3 acetylphenol, 4-acetylphenol, 2-methysulfonylmethane, 3 methysulfonylmethane, 3-chloro-4-methansulfonate the XI, 4 methanesulfonate, 2-econsultancy, 3 acanaloniidae, 4-econsultancy, 2-ethoxycarbonylmethoxy, 3 methoxycarbonylbenzyl, 4-methoxycarbonylbenzyl, 2-ethoxycarbonylmethoxy, 3 ethoxycarbonylmethoxy, 4-ethoxycarbonylmethoxy, 2-hydroxyphenoxy, 3 hydroxyphenoxy, 4-hydroxyphenoxy, 2-hydroxyethyloxy, 3 hydroxymethylene, 4-hydroxyethyloxy, 2-hydroxyethoxy, 3 hydroxyethyloxy, 4-hydroxyethyloxy, 2-formylphenoxy, 3 formylphenoxy, 4-formylphenoxy, 2-(1-hydroxyethyl)phenoxy, 3-(1-hydroxyethyl)phenoxy, 4-(1-hydroxyethyl)phenoxy, 2,3-divergence, 2,5-divergence, 2,4-divergence, 2,6-divergence, 2-fervency, 3 fervency, 4-fervency, 2 di pharmacokinetic, 3 deformationally, 4-deformationally, 2-triftormetilfosfinov, 3 triftormetilfosfinov, 4-triftormetilfosfinov, 2-(1H-tetrazol-5-yl)phenoxy, 3-(1H-tetrazol-5-yl)phenoxy, 4-(1H-tetrazol-5-yl)phenoxy, 4-(2-methyl-2H-tetrazol-5-yl)phenoxy, 2-(oxadiazol-3-yl)phenoxy, 3-(oxadiazol-3-yl)phenoxy, 4-(oxadiazol-3-yl)phenoxy, 2-(5-metronidazol-3-yl)phenoxy, 3-(5-metronidazol-3-yl)phenoxy, 4-(5-metronidazol-3-yl)phenoxy, 2-methoxybenzenesulfonyl, 3-methoxybenzenesulfonyl, 4-methoxyphenylalanine, 2-methoxytrimethylsilane, 3-methoxybenzenesulfonyl, 4-methoxybenzenesulfonyl, 2-(5-oxo-4,5-dihydro[1,2,4]oxadi the ol-3-yl)phenoxy, 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 2-(N-hydroxyamino)phenoxy, 3-(N-hydroxyamino)phenoxy, 4-(N-hydroxyamino)phenoxy, 2'-forbiden-4-yloxy, pyridine-2-ylsulphonyl, pyridine-3-ylsulphonyl, pyridine-4-ylsulphonyl, pyridine-4-isalphanumeric-2-yloxy, pyridine-2-yloxy, pyridine-3-yloxy, pyridine-4-yloxy, 2-methoxypyridine-3-yloxy, 2-methoxypyridine-4-yloxy, 6-methoxypyridine-3-yloxy, 6-methoxypyridine-2-yloxy, 3-methoxypyridine-2-yloxy, 4-methoxypyridine-2-yloxy, 5-methoxypyridine-2-yloxy, 6-methoxypyridine-3-yloxy, 2-deformationen-3-yloxy, 4-deformationen-3-yloxy, 6-methylpyridin-2-ylsulphonyl, 5-methylpyridin-2-ylsulphonyl, 4-methylpyridin-2-ylsulphonyl, 3-methylpyridin-2-ylsulphonyl, 4-cyano-pyridine-3-yloxy, 6-cyano-pyridine-3-yloxy, 4-dimethylcarbamoyl-pyridine-3-yloxy, 6-methanesulfonyl-pyridine-3-yloxy, 6-econsultancy-pyridine-3-yloxy, 4-methanesulfonyl-pyridine-3-yloxy, 2-cyano-pyridine-3-yloxy, 2-dimethylcarbamoyl-pyridine-3-yloxy, 2-methanesulfonyl-pyridine-3-yloxy, 2-methylpyridin-3-ylsulphonyl, 2-chloropyridin-3-yloxy, 6-acetylamino-pyridin-3-yloxy, 2-oxo-2H-[1,3']bipyridine-6'-yloxy, 4-methylpyridin-3-ylsulphonyl, 5-methylpyridin-3-ylsulphonyl, 6-methylpyridin-3-ylsulphonyl, 2-methylpyridin-4-ylsulphonyl, 3-methylpyridin-4-ylsulphonyl, 4-methylpyridin-3-ilal is of IMT, 5-methylpyridin-3-ylsulphonyl, 6-methylpyridin-3-ylsulphonyl, 2-methylpyridin-3-ylsulphonyl, 3-methylpyridin-2-ylsulphonyl, 4-methylpyridin-2-ylsulphonyl, 5-methylpyridin-2-ylsulphonyl, 6-methylpyridin-2-ylsulphonyl, 2-oxo-1,2-dihydropyridines-3-yloxy, 1-methyl-2-oxo-1,2-dihydropyridines-3-yloxy, 1-ethyl-2-oxo-1,2-dihydropyridines-3-yloxy, 5-bromopyridin-2-yloxy, 6-(5-methyl-[1,2,4]oxadiazol-3-yl-pyridine)-3-yloxy, 6-([1,2,4]oxadiazol-3-yl-pyridine)-3-yloxy, 1H-imidazol-2-ylsulphonyl, 1-methyl-1H-imidazol-2-ylsulphonyl, 4H-[1,2,4]triazole-3-ylsulphonyl, 4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl, 6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yloxy, 5-(2-oxo-oxadiazolidine-3-yl)pyridine-2-yloxy, 6-pyrazin-2-yl-pyridine-3-yloxy, 1-acetylpyrrolidine-2-yl, 2-acetylpyrrolidine-1-yl, 1-acetyl-3-fluoro-pyrrolidin-2-yl, 1-acetyl-5-methyl-pyrrolidin-2-yl, 1-acetylpiperidine-2-Il, 1-ethylcarboxyl-pyrrolidin-2-yl, 2-ethylcarboxyl-pyrrolidin-1-yl, 1-ethylcarboxyl-piperidine-2-yl, 1-n-propylboronic-pyrrolidin-2-yl, 2-n-propylboronic-pyrrolidin-2-yl, 1-n-propylboronic-piperidine-2-yl, 1-isopropyl-pyrrolidin-2-yl, 2-isopropyl-pyrrolidin-1-yl, 1-isopropyl-piperidine-2-yl, 1-hydrooximethylcarbamil-pyrrolidin-2-yl, 2-hydrooximethylcarbamil-pyrrolidin-1-yl, 1-hydrooximethylcarbamil-piperidine-2-yl, 1-hydroxymethyluracil-pyrrolidin-2-yl, 2-hydroxymethyluracil-pyrrolidin-1-yl, 1-hydroxymethyluracil-piperidine-2-yl, 1-methoxymethyl arbonyl-pyrrolidin-2-yl, 2-methoxyethylamine-pyrrolidin-1-yl, 1-ethoxymethylene-piperidine-2-yl, 1-ethoxymethylene-pyrrolidin-2-yl, 2-ethoxymethylene-pyrrolidin-1-yl, 1-ethoxymethylene-piperidine-2-yl, 1-methylpyrrolidine-2-yl, 2-methylpyrrolidine-1-yl, 1-methylpiperidin-2-yl, 1-ethylpyrrolidin-2-yl, 2-ethylpyrrolidin-1-yl, 1-ethylpiperidine-2-yl, 1-phenylcarbinol-pyrrolidin-2-yl, 2-phenylcarbamoyl-pyrrolidin-1-yl, phenylcarbinol-piperidine-2-yl, 1-ventilkappen-pyrrolidin-2-yl, 2-ventilkappen-pyrrolidin-1-yl, 1-ventilkappen-piperidine-2-yl, 1-benzylcarbamoyl-pyrrolidin-2-yl, 2-benzylcarbamoyl-pyrrolidin-1-yl, 1-benzylcarbamoyl-piperidine-2-yl, 1-dimethylaminomethylene-pyrrolidin-2-yl, 2-dimethylaminomethylene-pyrrolidin-1-yl, 1-dimethylaminomethylene-piperidine-2-yl, 1-methylaminomethyl-pyrrolidin-2-yl, 2-methylaminomethyl-pyrrolidin-1-yl, 1-methylaminomethyl-piperidine-2-yl, 1-cyclohexylcarbonyl-pyrrolidin-2-yl, 2-cyclohexylcarbonyl-pyrrolidin-1-yl, 1-yl-piperidine-2-yl, 1-cyclopentanecarbonyl-pyrrolidin-2-yl, 2-cyclopentanecarbonyl-pyrrolidin-1-yl, 1-cyclopentanecarbonyl-piperidine-2-yl, 1-(1-methyl-3-oxobutyryl)pyrrolidin-2-yl, 2-(1-methyl-3-oxobutyryl)pyrrolidin-1-yl, 1-(1-methyl-3-oxobutyryl)piperidine-2-yl, 1-methanesulfonyl-pyrrolidin-2-yl, 2-methanesulfonyl-pyrrolidin-1-yl, 1-methanesulfonyl-piperidine-2-yl, 1-canalphone-pyrrolidin-2-yl, 2-econsultancy-pyrrolidin-1-yl, 1-econsultancy-piperidine-2-yl, 1-isopropylphenyl-pyrrolidin-2-yl, 2-isopropylphenyl-pyrrolidin-1-yl, 1-isopropylphenyl-piperidine-2-yl, 1-carbarnoyl-pyrrolidin-2-yl, 2-carbarnoyl-pyrrolidin-1-yl, 1-carbarnoyl-piperidine-2-yl, 1-carbamoylmethyl-pyrrolidin-2-yl, 2-carbamoylmethyl-pyrrolidin-1-yl, 1-carbamoylmethyl-piperidine-2-yl, 1-carbamoylethyl-pyrrolidin-2-yl, 2-carbamoylethyl-pyrrolidin-1-yl, 1-carbamoylethyl-piperidine-2-yl, 1-(pyrrolidin-2-ylcarbonyl)pyrrolidin-2-yl, 2-(pyrrolidin-2-ylcarbonyl)pyrrolidin-1-yl, 1-(pyrrolidin-2-ylcarbonyl)-piperidine-2-yl, 1-(pyrimidinyl-2-yl)pyrrolidin-2-yl, 2-(pyrimidinyl-2-yl)pyrrolidin-1-yl, 1-(pyrimidinyl-2-yl)piperidine-2-yl, 1-(pyrazinyl-2-yl)pyrrolidin-2-yl, 2-(pyrazinyl-2-yl)pyrrolidin-1-yl, 1-(pyrazinyl-2-yl)piperidine-2-yl, 1-(pyridyl-2-yl)pyrrolidin-2-yl, 2-(pyridyl-2-yl)pyrrolidin-1-yl, 1-(pyridyl-2-yl)piperidine-2-yl, 1-(pyridyl-3-yl)pyrrolidin-2-yl, 2-(pyridyl-3-yl)pyrrolidin-1-yl, 1-(pyridyl-3-yl)piperidine-2-yl, 1-trifloromethyl-pyridine-2-yl, 2-trifloromethyl-pyrrolidin-1-yl, 1-trifloromethyl-piperidine-2-yl, 1-(2-hydroxyacetic)pyrrolidin-2-yl, 2-(2-hydroxyacyl)pyrrolidin-1-yl, 1-(2-hydroxyacyl)piperidine-2-yl, 1-(2-methylaminomethyl)pyrrolidin-2-yl, 2-(2-methylaminomethyl)pyrrolidin-1-yl, 1-(2-methylaminomethyl)piperidine-2-yl, 1-(2-dimethylaminoacetyl)pyrrolidin-2-yl, 2-(2-dimethy aminoacetyl)pyrrolidine-1-Il, 1-(2-dimethylaminoacetyl)piperidine-2-yl, 1-n-propylaminoethyl-pyrrolidin-2-yl, 2-n-propylaminoethyl-pyrrolidin-1-yl, 1-n-propylaminoethyl-piperidine-2-yl, 1-isopropylaminoethyl-pyrrolidin-2-yl, 2-isopropylaminoethyl-pyrrolidin-1-yl, 1-isopropylaminoethyl-piperidine-2-yl.

Ring A represents A 5 - or 6-membered nitrogen-containing aromatic heterokonta formula (II), optionally having in the ring 1 to 3 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (excluding the nitrogen atom N* in formula (II):

or represents a group of 5 - or 6-membered aromatic heterokonta condensed with a phenyl or pyridium.

X represents a carbon atom or a nitrogen atom.

More specifically, 5 - or 6-membered nitrogen-containing aromatic heterokonta for ring A includes, for example, thiazolyl, imidazolyl, isothiazolin, thiadiazolyl, triazolyl, oxazolyl, oxadiazolyl, isoxazolyl, pyrazinyl, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl. Which one is preferable thiazolyl, thiadiazolyl, isoxazolyl, pyrazinyl, pyridyl, pyridazinyl, triazolyl or pyrazolyl, and more preferred are pyridyl, pyrazinyl, thiazolyl, thiadiazolyl, isoxazolyl or pyrazolyl.

More specifically, the dual ring of 5 - or 6-membered nitrogen-containing aromaticheskogo the ring, condensed with a phenyl or pyridium, for ring A includes, for example, indolyl, benzimidazolyl, benzoxazolyl, peridotites, benzothiazolyl.

Ring A is preferably a 5 - or 6-membered nitrogen-containing aromatic heterokonta.

The ring A can be in the ring 1 or 2 substituent listed above for R3. In the case where the ring A has two such substituent, they may be the same or different.

Specifically, R3includes, for example, methyl, ethoxy, hydroxymethyl, methoxycarbonyl, methoxymethyl, aminomethyl, cyano, acetyl, fluorine, chlorine, bromine and deformity.

From the above, ring a ring A can be substituted by 1-3 R3) more specifically includes, for example, 3H-imidazol-4-yl, 1H-imidazol-2-yl, [1,2,4]triazole-3-yl, [1,2,3]triazole-4-yl, pyrazole-3-yl, pyrazole-1-yl, pyridine-2-yl, pyrazin-2-yl, oxazol-2-yl, oxazol-4-yl, [1,2,4]thiadiazole-5-yl, [1,2,4]thiadiazole-3-yl, thiazol-2-yl, thiazol-4-yl, [1,2,5]thiadiazole-3-yl, pyrrol-2-yl, isothiazol-3-yl, isoxazol-3-yl, 4-methyl-thiazol-2-yl, 4-hydroxymethyl-thiazol-2-yl, 4-ethoxycarbonyl-thiazol-2-yl, 4-methoxymethyl-thiazol-2-yl, 4-aminomethyl-thiazol-2-yl, 4-cyano-thiazol-2-yl, 4-cyano-thiazol-2-yl, 4-fluoro-thiazol-2-yl, imidazol-2-yl, 4-methyl-imidazol-2-yl, 4-methoxycarbonyl-imidazol-2-yl, isothiazol-3-yl, 4-hydroxymethyl-isothiazol-3-yl, [1,3,4]thiadiazole-2-yl, 5-acetyl-[1,3,4]thiadiazole-2-yl, [1,2,4]triazole-2-yl, 5-hydro is simetal-[1,2,4]triazole-3-Il, 4-methyl-pyridine-2-yl, 4-methoxymethyl-imidazol-2-yl, 4-acetyl-imidazol-2-yl, 5-hydroxymethyl-imidazol-2-yl, 5-methyl-[1,3,4]thiadiazole-2-yl, 5-fluoro[1,3,4]thiadiazole-2-yl, 5-methyl-[1,2,4]triazole-2-yl, 5-acetyl-[1,2,4]triazole-3-yl, 4-methoxymethyl-isoxazol-2-yl, 5-methyl-isoxazol-3-yl, 5-hydroxymethyl-isoxazol-3-yl, 1-hydroxy-pyrazin-2-yl, 1-oxy-pyridine-2-yl, 5-methoxymethyl-isoxazol-3-yl, 5-methylcarbamoyl-isoxazol-3-yl, 5-chloro-isoxazol-3-yl, 5-aminomethyl-isoxazol-3-yl, 4-methyl-1H-pyrazole-3-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyridazin-3-yl, 6-methyl-pyridazin-3-yl, 2-methyl-thiazol-4-yl, thiazolo[5,4-b]pyridine-2-yl, 3-methyl[1,2,4]thiadiazolyl-5-yl, 1-methyl-1H-pyrazole-3-yl.

R2means hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6alkyl or -(CH2)1-4OH.

R2is preferably hydroxy, formyl, -CH3-aFa(preferably trifluoromethyl), -OCH3-aFa, halogen, C1-6alkyl, amino, CN, -(CH2)1-4OH; more preferably hydroxy, formyl, -CH3-Fa(preferably trifluoromethyl), -OCH3-aFa(preferably triptoreline), amino, halogen, -C1-6alkyl, CN or -(CH2)1-4OH, even more preferably hydroxy, formyl, amino, halogen (preferably fluorine, chlorine), -C1-6alkyl or -(CH2)1-4OH.

q denotes an integer from 0 to 2.

When q p the VNO 2, then R2may be the same or different.

Of the compounds of formula (I-0), however, compounds where one of X5represents an oxygen atom or a sulfur atom and the other X5represents a single bond, and compounds, where both X5represent a single bond, and R1represents aryl or 4-10-membered monocyclic or bicyclic heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, (R1may be substituted independently 1-3 R1and when heteroclita is aliphatic heterokonta, then he can have 1 or 2 double bonds), are excluded from the compounds according to the invention.

From the aforesaid formula (I) described group partial structures represented by the following formula (VII).

In the formula (VII) X1- X4each represent a carbon atom or a nitrogen atom, and X1- X4at least two are carbon atoms.

More preferably all X1- X4in the formula (VII) is represented by the carbon atoms.

In the preferred embodiment of the invention the compounds of formula (I-0) are compounds represented by the following formula (I-1):

[In the formula, R11represents phenyl, optionally substituted 1-3R 4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4), and X51represents-O-, -S-, -S(O)- or-S(O)2-, and other symbols have the above values].

"Phenyl, optionally substituted by 1-3 R4for R11represents phenyl which may be substituted by 1-3 specified R4.

"5 - or 6-membered nitrogen-containing aromatic heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom" for R11means 5 - or 6-membered monocyclic aromatic heterokonta specified for R1that has at least one nitrogen atom in the ring as a constituent heterokonta atom, and it specifically includes, for example, pyrrolyl, pyrazolyl, isoxazolyl, isothiazolin, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl.

X1;X2X3and X4in the formula (I-1) have the meanings indicated in the formula (I-0), and preferably all X1X2X3and X4represent carbon atoms.

R4the GRF is OLE (I-1) has the same values, and R4in the formula (I-0).

X51represents-O-, -S-, -S(O)- or-S(O)2-, preferably-O - or-S-, more preferably-O-.

Formula (I-1) has two groups, each of which is represented by-X51R11and they may be the same or different.

R11-X51in the formula (I-1) (R11may be substituted by 1-3 R4) concretely includes, for example, phenylsulfonyl, phenoxy, benzyloxy, 2-cianfrocca, 3 cianfrocca, 4-cianfrocca, 2-carbamoylphenoxy, 3 carbamoylphenoxy, 4-carbamoylphenoxy, 2-methylcarbamoylmethyl, 3 methylcarbamate, 4-methylcarbamoylmethyl, 2-dimethylcarbamate, 3 dimethylcarbonate, 4-dimethylcarbamate, 2-(pyrrolidin-1-carbonyl)phenoxy, 3-(pyrrolidin-1-carbonyl)phenoxy, 4-(pyrrolidin-1-carbonyl)phenoxy, 2-methoxyphenoxy, 3 methoxyphenoxy 4 methoxyphenoxy, 2-isopropylphenoxy, 3 isopropylphenoxy, 4-isopropylphenoxy, 2-methylphenoxy, 3 methylphenoxy, 4-methylphenoxy, 2-ethylenoxy, 3 ethylenoxy, 4-ethylenoxy, 2-acetylphenol, 3 acetylphenol, 4-acetylphenol, 2-methysulfonylmethane, 3 methanesulfonate, 4-methanesulfonate, 2-ethoxycarbonylmethoxy, 3 methoxycarbonylbenzyl, 4-methoxycarbonylbenzyl, 2-ethoxycarbonylmethoxy, 3 ethoxycarbonylmethoxy, 4-ethoxycarbonylmethoxy, 2-hydroxyphenoxy, 3 hydroxyphenoxy, 4-hydroxyphenoxy, 2-hydroxymet is phenoxy, 3 hydroxymethylene, 4-hydroxyethyloxy, 2-hydroxyethoxy, 3 hydroxyethyloxy, 4-hydroxyethyloxy, 2-formylphenoxy, 3 formylphenoxy, 4-formylphenoxy, 2-(1-hydroxyethyl)phenoxy, 3-(1-hydroxyethyl)phenoxy, 4-(1-hydroxyethyl)phenoxy, 2,5-divergence, 2,4-divergence, 2,3-divergence, 2,6-divergence, 2-fervency, 3 fervency, 4-fervency, 2-fluoro-6-carbamoylphenoxy, 2-deformationally, 3-deformationally, 4-deformationally, 2-triftormetilfosfinov, 3 triftormetilfosfinov, 4-triftormetilfosfinov, 2-cyano-6-fervency, 2-(1H-tetrazol-5-yl)phenoxy, 3-(1H-tetrazol-5-yl)phenoxy, 4-(1H-tetrazol-5-yl)phenoxy, 2-(oxadiazol-3-yl)phenoxy, 3-(oxadiazol-3-yl)phenoxy, 4-(oxadiazol-3-yl)phenoxy, 2-(5-metronidazol-3-yl)phenoxy, 3-(5-metronidazol-3-yl)phenoxy, 4-(5-metronidazol-3-yl)phenoxy, 2-methoxyphenylacetyl, 3-methoxybenzenesulfonyl, 4-methoxyphenylalanine, 2-methoxytrimethylsilane, 3-methoxybenzenesulfonyl, 4-methoxybenzenesulfonyl, 2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 2-(N-hydroxyamino)phenoxy, 3-(N-hydroxyamino)phenoxy, 4-(N-hydroxyamino)phenoxy, pyridine-2-ylsulphonyl, pyridine-3-ylsulphonyl, pyridine-4-ylsulphonyl, pyridine-2-yloxy, pyridine-3-yloxy, pyridine-4-yloxy, 2-way shall Sipiagin-3-yloxy, 2-methoxypyridine-4-yloxy, 6-methoxypyridine-3-yloxy, 6-methoxypyridine-2-yloxy, 3-methoxypyridine-2-yloxy, 4-methoxypyridine-2-yloxy, 5-methoxypyridine-2-yloxy, 2-deformationen-3-yloxy, 6-methylpyridin-2-ylsulphonyl, 5-methylpyridin-2-ylsulphonyl, 4-methylpyridin-2-ylsulphonyl, 3-methylpyridin-2-ylsulphonyl, 4-cyano-pyridine-3-yloxy, 4-dimethylcarbamoyl-pyridine-3-yloxy, 4-methanesulfonyl-pyridine-3-yloxy, 2-cyano-pyridine-3-yloxy, 2-dimethylcarbamoyl-pyridine-3-yloxy, 2-methanesulfonyl-pyridine-3-yloxy, 2-methylpyridin-3-ylsulphonyl, 4-methylpyridin-3-ylsulphonyl, 5-methylpyridin-3-ylsulphonyl, 6-methylpyridin-3-ylsulphonyl, 2-methylpyridin-4-ylsulphonyl, 3-methylpyridin-4-ylsulphonyl, 4-methylpyridin-3-ylsulphonyl, 5-methylpyridin-3-ylsulphonyl, 6-methylpyridin-3-ylsulphonyl, 2-methylpyridin-3-ylsulphonyl, 3-methylpyridin-2-ylsulphonyl, 4-methylpyridin-2-ylsulphonyl, 5-methylpyridin-2-ylsulphonyl, 6-methylpyridin-2-ylsulphonyl, 2-oxo-1,2-dihydropyridines-3-yloxy, 1-methyl-2-oxo-1,2-dihydropyridines-3-yloxy, 1-ethyl-2-oxo-1,2-dihydropyridines-3 iloxi, 1H-imidazol-2-ylsulphonyl, 1-methyl-1H-imidazol-2-ylsulphonyl, 4H-[1,2,4]triazole-3-ylsulphonyl or 4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl.

In a preferred embodiment, compounds according to the invention both R11in the formula (I-1) represent finely, optionally substituted by 1-3 R4.

In another preferred variant is NTE compounds according to the invention both R 11in the formula (I-1) represent 5 - or 6-membered monocyclic nitrogen-containing aromatic heterokonta, each of which has a ring from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing heteroaromatic ring may be substituted by 1-3 R4).

In another preferred embodiment, compounds according to the invention one R11in the formula (I-1) is phenyl, optionally substituted by 1-3 R4and the other R11represents 5 - or 6-membered monocyclic nitrogen-containing aromatic heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4).

In another preferred embodiment of the invention the compounds of formula (I-0) are compounds represented by the following formula (I-2):

[In the formula, R12is a 5-7 membered nitrogen-containing heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (R12may be substituted by 1-3 R4and when R 12represents aliphatic heterokonta, then he can have 1 or 2 double bonds in the ring); X52represents-O-, -S-, -S(O)-, -S(O)2- or a single bond, and the other symbols have the above values].

"4-7-membered nitrogen-containing heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom" for R12maybe 4-7-membered monocyclic heterokonta for R1that has at least one nitrogen atom in heteroclite, and it specifically includes, for example, azetidine, pyrrolidine, piperidinyl, azepane, piperazinil, morpholino, thiomorpholine, homopiperazine, imidazolidinyl, pyrazolidine, pyrrolyl, pyrazolyl, isoxazolyl, isothiazolin, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl.

R12may have from 1 to 3 R4as deputies.

When R12it has 2 or 3 R4as substituents, they may be the same or different.

Of the groups mentioned here above for R4groups preferred as substituents for R12represent-C(O)-C1-6Ala is l (C 1-6the alkyl may be substituted with halogen, hydroxy, -N(R51R52, -O-C1-6the alkyl or phenyl), -C(O)-phenyl, -C(O)-C3-7cycloalkyl, -C(O)-O-C1-6alkyl, -C(O)-N(R51R52- 1-6alkyl, aromatic heterokonta, -S(O)2-N(R51R52or-S(O)2-C1-6alkyl.

The substituents for R12specifically include, for example, acetyl, ethylcarboxyl, propylmalonic, isopropylcarbonate, hydrooximethylcarbamil, hydroxymethyluracil, methoxyethylamine, ethoxymethylene, methyl, ethyl, phenylcarbinol, ventilkappen, benzylcarbamoyl, dimethylaminomethylene, methylaminomethyl, cyclohexylcarbonyl, cyclopentanecarbonyl, 1-methyl-3-oxobutyryl, methanesulfonyl, econsultancy, isopropylphenyl, carbarnoyl, carbamoylmethyl, carbamoylethyl, pyrrolidin-2-carbonyl, pyrimidinyl, pyrazinyl, pyridyl, triptorelin, 2-hydroxyacetic, 2-methylaminoethanol, 2-dimethylaminoacetyl, 2-ethylaminoethanol, n-propylaminoethyl, isopropylaminoethyl, oxo, methyl, ethyl, isopropyl.

X51in the formula (I-2) is preferably-O - or-S is specified here above for X51more preferably-O-.

X52in the formula (I-2) represents-O-, -S-, -S(O)-, -S(O)2- or a single bond.

In the case where R12represents a 4-7-membered saturated nitrogen-containing Alif the political heterokonta, having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4), then X52represents preferably a single bond.

In the case where R12is a 5-7 membered nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds, (5-7-membered heterokonta may be substituted by 1-3 R4), then X52is preferably-O-, -S-, -S(O)- or-S(O)2-, more preferably-O-.

"A 4-7-membered saturated nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom,for R12concretely includes, for example, azetidine, pyrrolidine, piperidine, piperidinyl homopiperazine, azepane, piperazinil, morpholino, thiomorpholine, homopiperazine, imidazolidinyl, pyrazolidine. Of them preferred azetidinol, pyrrolidinyl or piperidinyl; preferred pyrrolidinyl, piperidinyl, homopiperazine; and more preferred group of formula (III-1):

or of the formula (III-2):

[in the formula, n denotes an integer from 1 to 3, and R41has the same meaning as R4]; and even more preferred group of formula (III-3):

[in the formulas, R4has the above values, the following formula (VIII):

denotes the binding site of in which the group is associated with X53].

"A 4-7-membered saturated nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4for R12includes specifically, for example, 1-acetylpyrrolidine-2-yl, 2-acetylpyrrolidine-1-yl, 1-acetyl-3-ftorpirimidinu-2-yl, 1-acetyl-5-methyl-pyrrolidin-2-yl, 1-acetylpiperidine-2-yl, 1-amilcare the l-pyrrolidin-2-yl, 2-ethylcarbodiimide-1-yl, 1-ethylcarboxyl-piperidine-2-yl, 1-n-propylboronic-pyrrolidin-2-yl, 2-n-propylboronic-pyrrolidin-2-yl, 1-n-propylboronic-piperidine-2-yl, 1-isopropyl-pyrrolidin-2-yl, 2-isopropyl-pyrrolidin-1-yl, 1-isopropyl-piperidine-2-yl, 1-hydrooximethylcarbamil-pyrrolidin-2-yl, 2-hydrooximethylcarbamil-pyrrolidin-1-yl, 1-hydrooximethylcarbamil-piperidine-2-yl, 1-hydroxymethyluracil-pyrrolidin-2-yl, 2-hydroxymethyluracil-pyrrolidin-1-yl, 1-hydroxymethyluracil-piperidine-2-yl, 1-ethoxymethylene-pyrrolidin-2-yl, 2-methoxyethylamine-pyrrolidin-1-yl, 1-ethoxymethylene-piperidine-2-yl, 1-ethoxymethylene-pyrrolidin-2-yl, 2-ethoxymethylene-pyrrolidin-1-yl, 1-ethoxymethylene-piperidine-2-yl, 1-methylpyrrolidine-2-yl, 2-methylpyrrolidine-1-yl, 1-methylpiperidin-2-yl, 1-ethylpyrrolidin-2-yl, 2-ethylpyrrolidin-1-yl, 1-ethylpiperidine-2-yl, 1-phenylcarbamoyl-pyrrolidin-2-yl, 2-phenylcarbamoyl-pyrrolidin-1-yl, 1-phenylcarbamoyl-piperidine-2-yl, 1-ventilkappen-pyrrolidin-2-yl, 2-ventilkappen-pyrrolidin-1-Il, 1-ventilkappen-piperidine-2-yl, 1-benzylcarbamoyl-pyrrolidin-2-yl, 2-benzylcarbamoyl-pyrrolidin-1-yl, 1-benzylcarbamoyl-piperidine-2-yl, 1-dimethylaminomethylene-pyrrolidin-2-yl, 2-dimethylaminomethylene-pyrrolidin-1-yl, 1-dimethylaminomethylene-piperidine-2-yl, 1-methylaminomethyl-pyrrolidin-2-yl, 2-meth is aminomethylpropanol-pyrrolidin-1-yl, 1-yl-piperidine-2-yl, 1-cyclohexylcarbonyl-pyrrolidin-2-yl, 2-cyclohexylcarbonyl-pyrrolidin-1-yl, 1-cyclohexylcarbonyl-piperidine-2-yl, 1-cyclopentanecarbonyl-pyrrolidin-2-yl, 2-cyclopentanecarbonyl-pyrrolidin-1-yl, 1-cyclopentanecarbonyl-piperidine-2-yl, 1-(1-methyl-3-oxobutyryl)pyrrolidin-2-yl, 2-(1-methyl-3-oxobutyryl)pyrrolidin-1-yl, 1-(1-methyl-3-oxobutyryl)piperidine-2-yl, 1-methanesulfonyl-pyrrolidin-2-yl, 2-methanesulfonyl-pyrrolidin-1-yl, 1-methanesulfonyl-piperidine-2-yl, 1-econsultancy-pyrrolidin-2-yl, 2-econsultancy-pyrrolidin-1-yl, 1-econsultancy-piperidine-2-yl, 1-isopropylphenyl-pyrrolidin-2-yl, 2-isopropylphenyl-pyrrolidin-1-yl, 1-isopropylphenyl-piperidine-2-yl, 1-carbarnoyl-pyrrolidin-2-yl, 2-carbarnoyl-pyrrolidin-1-yl, 1-carbarnoyl-piperidine-2-yl, 1-carbamoylmethyl-pyrrolidin-2-yl, 2-carbamoylmethyl-pyrrolidin-1-yl, 1-carbamoylmethyl-piperidine-2-yl, 1-carbamoylethyl-pyrrolidin-2-yl, 2-carbamoylethyl-pyrrolidin-1-yl, 1-carbamoylethyl-piperidine-2-yl, 1-(pyrrolidin-2-ylcarbonyl)pyrrolidin-2-yl, 2-(pyrrolidin-2-ylcarbonyl)pyrrolidin-1-yl, 1-(pyrrolidin-2-ylcarbonyl)-piperidine-2-yl, 1-(pyrimidinyl-2-yl)pyrrolidin-2-yl, 2-(pyrimidinyl-2-yl)pyrrolidin-1-yl, 1-(pyrimidinyl-2-yl)piperidine-2-yl,1-(pyrazinyl-2-yl)pyrrolidin-2-yl, 2-(pyrazinyl-2-yl)pyrrolidin-1-yl, 1-(pyrazinyl-2-yl)piperidine-2-yl, 1-(pyridyl-2-yl)pyrrolidin-2-yl, 2-(pyridyl-2-the l)pyrrolidin-1-yl, 1-(pyridyl-2-yl)piperidine-2-yl, 1-(pyridyl-3-yl)pyrrolidin-2-yl, 2-(pyridyl-3-yl)pyrrolidin-1-yl, 1-(pyridyl-3-yl)piperidine-2-yl, 1-trifloromethyl-pyridine-2-yl, 2-trifloromethyl-pyrrolidin-1-yl, 1-trifloromethyl-piperidine-2-yl, 1-(2-hydroxyacyl)pyrrolidin-2-yl, 2-(2-hydroxyacyl)pyrrolidin-1-yl, 1-(2-hydroxyacyl)piperidine-2-yl, 1-(2-methylaminomethyl)pyrrolidin-2-yl, 2-(2-methylaminomethyl)pyrrolidin-1-yl, 1-(2-methylaminomethyl)piperidine-2-yl, 1-(2-dimethylaminoacetyl)pyrrolidin-2-yl, 2-(2-dimethylaminoacetyl)pyrrolidin-1-yl, 1-(2-dimethylaminoacetyl)piperidine-2-yl, 1-n-propylaminoethyl-pyrrolidin-2-yl, 2-n-propylaminoethyl-pyrrolidin-1-yl, 1-n-propylaminoethyl-piperidine-2-yl, 1-isopropylaminoethyl-pyrrolidin-2-yl, 2-isopropylaminoethyl-pyrrolidin-1-yl, 1-isopropylaminoethyl-piperidine-2-yl.

"5-7-membered nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds" for R12includes specifically, for example, groups of the formula (IX):

"5-7-membered nitrogen-containing aliphatic heterokonta having as atom, the composition of the managing heterokonta, at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds, (nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4for R12includes specifically, for example, 1-methyl-2-oxo-1,2-dihydropyridin, 2-oxo-1,2-dihydropyridin, 1-ethyl-2-oxo-1,2-dihydropyridin, 1-isopropyl-2-oxo-1,2-dihydropyridin, 1-propyl-2-oxo-1,2-dihydropyridin.

R11-X51- (R11may be substituted by 1-3 R4in the formula (I-2) can have the same values as in formula (I-1). One of them specifically preferred, for example, 5-bromopyridin-2-yloxy, 6-methanesulfonyl-pyridine-3-yloxy, 2-chloropyridin-3-yloxy, 4-hydroxyethoxymethyl-phenoxy, 4-methysulfonylmethane, 6-econsultancy-pyridine-3-yloxy, 6-cyano-3-yloxy, 6-acetylamino-pyridin-3-yloxy, 4-methoxymethyl-phenoxy, 4-(2-oxo-2H-pyridin-1-yl)phenoxy, 6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yloxy, 2'-forbiden-4-yloxy, 6-([1,2,4]-oxadiazol-3-yl)pyridine-3-yloxy, 6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yloxy, 4-(2-methyl-2H-tetrazol-5-elfenix), 6-methoxymethyl-pyridine-3-yloxy, 2-oxo-2H-[1,3']bipyridine-6'-yloxy, 5-(2-oxo-oxazolidinone-3-yl)pyridine-2-yloxy, 6-methylpyridin-3-yloxy, 6-pyrazin-2-espiridion-3-yloxy, 4-acetylphenol.

In before Occitania embodiment of the invention the compounds of formula (I-1) are compounds represented by the following formula (I-11):

[in the formula, the symbols have the above values].

In the formula (I-11), R11(R11may be substituted by 1-3 R4) may be the same as R11in the formula (I-1).

In the formula (I-11) X51is preferably-O - or-S-, more preferably-O-.

In the formula (I-11) X1and X3each independently represent a carbon atom or a nitrogen atom, but preferably both X1and X3represent carbon atoms.

In the formula (I-11) R11-X51- (R11may be substituted by 1-3 R4includes specifically, for example, methysulfonylmethane, 3 methanesulfonate, 2-methoxyphenoxy, 3 methoxyphenoxy, 2-acetylphenol, 3 acetylenics, 2-carbamoylphenoxy, 3 carbamoylphenoxy, phenoxy, 2-cyano-6-fervency, 2-methylphenoxy, 3 methylphenoxy, 2-fervency, 3 fervency, 2,3-divergence, 2,4-divergence, 2,5-divergence, 2,6-divergence, pyridine-2-yloxy, pyridine-3-yloxy, 2-methoxypyridine-3-yloxy, 2-deformationen-3-yloxy. Of them, preferred 2-methanesulfonate, 2-methoxyphenoxy, 2-acetylphenol, 2-carbamoylphenoxy, phenoxy, 2-cyano-6-fervency, 2-methylphenoxy, 2-fervency, 2,3-divergence, 2,6-divergence, pyridine-3-yloxy, 2-methoxypyridine-3-yloxy, 2-deformationen-3-yloxy.

In d the natives preferred embodiment of the invention the compounds of formula (I-1) are compounds represented by the following formula (I-12):

[in the formula, the symbols have the above values].

In the formula (I-12), R11(R11may be substituted by 1-3 R4) may be the same as R11in the formula (I-1).

In the formula (I-12) X51is preferably-O - or-S-, more preferably-O-.

In the formula (I-12) X1and X3each independently represent a carbon atom or a nitrogen atom, but preferably both X1and X3represent carbon atoms.

In the formula (I-12) R11-X51- (R11may be substituted by 1-3 R4) specifically includes 2-carbamoylphenoxy, 3 carbamoylphenoxy, 4-carbamoylphenoxy, 2-cianfrocca, 3 cianfrocca, 4-cianfrocca, 2-methoxyphenoxy, 3 methoxyphenoxy, 4-methoxyphenoxy, 2-methysulfonylmethane, 3 methanesulfonate, 4-methanesulfonate, 2-(pyrrolidin-1-carbonyl)phenoxy, 3-(pyrrolidin-1-carbonyl)phenoxy, 4-(pyrrolidin-1-carbonyl)phenoxy, pyridine-2-yloxy, pyridine-3-yloxy, pyridine-4-yloxy, 2-methylcarbamoylmethyl, 3 methylcarbamate, 4-methylcarbamoylmethyl, 2-dimethylcarbamate, 3 dimethylcarbonate, 4-dimethylcarbamate, 2-(oxadiazol-3-yl)phenoxy, 2-ethoxycarbonylmethoxy, 3 methoxycarbonylbenzyl, 4-methoxycarbonylbenzyl, 2-acetylphenol, 3-and is ethylenoxy, 4 acetylenics, 2-ethoxycarbonylmethoxy, 3 ethoxycarbonylmethoxy, 4-ethoxycarbonylmethoxy, 2-n-hydroxyamino-phenoxy, 3-N-hydroxyamino-phenoxy, 4-N-hydroxyamino-phenoxy, 2-hydroxymethyl-phenoxy, 3-hydroxymethyl-phenoxy, 4-hydroxymethyl-phenoxy, 2-(2H-tetrazol-5-yl)phenoxy, 3-(2H-tetrazol-5-yl)phenoxy, 4-(2H-tetrazol-5-yl)phenoxy, 2-cyano-pyridin-3-yloxy, 4-cyano-pyridine-3-yloxy, 2-carbarnoyl-pyridine-3-yl, 2-deformedarse-pyridine-3-yloxy, 4-carbarnoyl-pyridine-3-yl, 2-(5-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 2-formylphenoxy, 3 formylphenoxy, 4-formylphenoxy.

Of them, for example, one of R11-X51is preferably 2-carbamoylphenoxy, 4-carbamoylphenoxy, 2-cianfrocca, 4-cianfrocca, 2-methoxyphenoxy, 4-methoxyphenoxy, 2-methanesulfonate, 4-methysulfonylmethane, pyridine-2-yloxy, pyridine-3-yloxy, pyridine-4-yloxy, 2-cyano-pyridine-3-yloxy, 2-deformedarse-pyridine-3-yloxy, 4-cyano-pyridine-3-yloxy, 2-carbarnoyl-pyridine-3-yloxy, 4-carbarnoyl-pyridine-3-yloxy, 5-cyano-pyridine-3-yloxy, 4-cyano-pyridine-3-yloxy, 5-carbarnoyl-pyridine-3-yloxy, 4-carbarnoyl-pyridine-3-yloxy, 2-methylcarbamoylmethyl, 4-methylcarbamoylmethyl, 2-dimethylcyclohexane, 4-dimethylcarbamate, 2-(oxadiazol-3-yl)phenoxy, 2-labels is carbonfinance, 4 ethoxycarbonylmethoxy, 2-acetylphenol, 4-acetylphenol, 2-ethoxycarbonylphenyl, 4-ethoxycarbonylmethoxy, 2-N-hydroxyguanidine-phenoxy, 4-N-hydroxyamino-phenoxy, 2-hydroxymethyl-phenoxy, 4-hydroxymethyl-phenoxy, 2-deformedarse-pyridine-3-yloxy, 2-(2H-tetrazol-5-yl)phenoxy, 4-(2H-tetrazol-5-yl)phenoxy, 2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 2-formylphenoxy, 4-formylphenoxy; more preferably 2-carbamoylphenoxy, 2-cianfrocca, 2-methoxyphenoxy, 2-methysulfonylmethane, pyridine-3-yloxy, 2-deformedarse-pyridine-3-yloxy, 2-methylcarbamoylmethyl, 2-dimethylcarbamate, 2-(oxadiazol-3-yl)phenoxy, 2-ethoxycarbonylmethoxy, 2-acetylphenol, 2-ethoxycarbonylmethoxy, 2-n-hydroxyamino-phenoxy, 2-cyano-pyridine-3-yloxy, 2-deformedarse-pyridine-3-yloxy, 2-carbarnoyl-pyridine-3-yloxy, 2-hydroxymethyl-phenoxy, 2-(2H-tetrazol-5-yl)phenoxy, 2-deformedarse-pyridine-3-yloxy, 2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 2-formylphenoxy.

For example, the other R11-X51- is preferably 3 carbamoylphenoxy, 4-carbamoylphenoxy, 3 cianfrocca, 4-cianfrocca, 3 methoxyphenoxy, 4-methoxyphenoxy, 3-(pyrrolidin-1-carbonyl)phenoxy, 4-(pyrrolidin-1-carbonyl)phenoxy, 3 methanesulfonate, 4-methysulfonylmethane, pyridine-2-yloxy, pyridine-3-yloxy, pyridine-yloxy, 2 deformedarse-pyridine-3-yloxy, 3 methylcarbamate, 4-methylcarbamoylmethyl, 5-cyano-pyridine-3-yloxy, 4-cyano-pyridine-3-yloxy, 5-carbarnoyl-pyridine-3-yloxy, 4-carbarnoyl-pyridine-3-yloxy, 3 dimethylcarbonate, 4-dimethylcarbamate, 4-(oxadiazol-3-yl)phenoxy, 3 methoxycarbonylbenzyl, 4-ethoxycarbonylphenyl, 3 acetylphenol, 4-acetylphenol, 3 ethoxycarbonylmethoxy, 4-ethoxycarbonylmethoxy, 3-N-hydroxyamino-phenoxy, 4-N-hydroxyamino-phenoxy, 3-hydroxymethyl-phenoxy, 4-hydroxymethyl-phenoxy, 3-(2H-tetrazol-5-yl)phenoxy, 4-(2H-tetrazol-5-yl)phenoxy, 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 3-formylphenoxy, 4-formylphenoxy; more preferably 4 carbamoylphenoxy, 4-cianfrocca, 4-methoxyphenoxy, 4-methysulfonylmethane, pyridine-3-yloxy, 4-methylcarbamoylmethyl, 4-dimethylcarbamate, 4-(oxadiazol-3-yl)phenoxy, 4-methoxycarbonylbenzyl, 4-acetylphenol, 4-ethoxycarbonylphenyl, 4-N-hydroxyamino-phenoxy, 4-hydroxymethyl-phenoxy, 4-cyano-pyridine-3-yloxy, 2-deformedarse-pyridine-3-yloxy, 4-carbarnoyl-pyridine-3-yloxy, 4-(2H-tetrazol-5-yl)phenoxy, 4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenoxy, 4-formylphenoxy.

In another preferred embodiment, compounds according to the invention one R1in the formula (I-0) represents phenyl, optionally substituted by the first 1-3 R 4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4), and the other R1is a 5-7 membered nitrogen-containing heterokonta having as heteroatom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms from 1 to 4 heteroatoms selected from nitrogen atom, sulfur atom and oxygen atom.

5-7-membered nitrogen-containing heterokonta may be 5 - or 6-membered nitrogen-containing aromatic heterokonta or a 5-7 membered nitrogen-containing aliphatic heterokonta.

5 - or 6-membered nitrogen-containing aromatic heterokonta includes specifically, for example, pyrrolyl, furyl, thienyl, pyrazolyl, isoxazolyl, isothiazolin, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl.

5-7-membered nitrogen-containing aliphatic heterokonta includes specifically, for example, azetidine, pyrrolidine, piperidine, piperidinyl, azepane, piperazinil, morpholino, thiomorpholine, homopiperazine, imidazolidinyl, pyrazolidine.

Heterokonta may be substituted by 1-3 R4

In yet another preferred embodiment of the invention compounds according to the invention is represented by formula (I-0), and one R1represents phenyl, optionally substituted by 1-3 R4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4), and the other R1represents 5 - or 6-membered nitrogen-containing hetero-aromatic ring having as heteroatom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms from 1 to 4 heteroatoms selected from nitrogen atom, sulfur atom and oxygen atom.

5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom can be the same as specified here above.

In yet another preferred embodiment of the invention compounds according to the invention is represented by formula (I-0), and one R1represents phenyl, optionally substituted by 1-3 R4or represents 5 - or 6-membered nitrogen-containing the aromatic heterokonta, having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4), and the other R1is a 5-7 membered nitrogen-containing aliphatic heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from nitrogen atom, sulfur atom and oxygen atom (nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R and can be in the ring 1 or 2 double bonds).

Of the compounds of formula (I-0) is specifically preferred, for example:

5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-(methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-(1-m the Teal-1H-pyrazole-3-yl)-1H-benzimidazole,

5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-(1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,3-debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-yloxy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,4-debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,5-debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-herperidin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-herperidin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-chloropyridin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-chloropyridin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-cyano-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-ETANA hanil-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole;

5-(2-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole,

5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-(tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-deformationen-3-yloxy)-6-(3-chloro-4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-fluoro-phenoxy)-2-(pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-etancelin the l-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-(1H-pyrazole-3-yl)-1H-benzimidazole,

4-(2-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,3-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,5-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(2-(6-(5-bromo-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-hydroxymethyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid,

2-hydroxy-1-(2-(6-(4-methanesulfonyl-1 phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(6-econsultancy-the feast of the Dean-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

2-fluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-methylamino-Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

N-(5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-yl)acetamide", she

1-(2-(2-(5-bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

N-(2-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)acetamide", she

6-(1-acetylpyrrolidine-2-yl)-5-(4-(methoxymethyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole monotropaceae,

1-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)pyridin-2(1H)-he,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

(2-(2-(5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl)methylamine,

6-(1-acetylpyrrolidine-2-yl)-5-((6-([1,2,4]-oxadi the evil-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(1-acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(1-acetyl-5-methylpyrrolidine-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(6-methoxypyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl,

2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxamid,

5'-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it,

3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it,

6-(1-acetylpyrrolidine-2-yl)-5-((6-methylpyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-pyrazin-2-espiridion-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetyl-3-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy-2-pyridin-2-yl-1H-benzimidazo the l

3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it,

6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-5-((6-pyrazin-2-espiridion-3-yl)oxy)-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)Etalon,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(5-methyl-[1,2,4]-oxadiazol-3-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

6-(1-acetyl-5-methylpyrrolidine-2-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

N-methyl-2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxetanone,

6-(1-acetyl-5-methylpyrrolidine-2-yl)-5-((6-(methoxymethyl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon,

1-(1-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon,

1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon or

1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)-4-fluoro-pyrrolidin-2-yl)alanon or their pharmaceutically acceptable salts.

New 2-heteroaryl-substituted benzimidazole derivatives according to the invention can be in the form f is rmaceuticals acceptable salts. Salt include additive salts with acids and additive salts with bases.

Depending on the type of substituents in these compounds according to the invention include stereoisomers and tautomers, such as optical isomers, diastereomers isomers and geometric isomers. Needless to say that the compounds according to the invention encompass all of these isomers. In addition, needless to say that the compounds according to the invention cover all mixtures of such isomers.

Since the compounds according to the invention have the effect of activating glucokinase, they are applicable as a medicinal and/or prophylactic agents against diabetes and additionally as a drug and/or prophylactic agents against diabetic complications.

Mentioned here diabetes complications mean disease complicated by diabetes, including diabetic nephropathy, diabetic retinopathy, diabetic arteriosclerosis.

Compounds according to the invention is applicable in both types of diabetes, insulin-dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM).

Insulin-dependent diabetes mellitus (IDDM) is due to the genetic predisposition to reduced insulin secretion and insulin resistance of skeletal musculature that promoterwise insulin resistance, causing expect the group and essentially treated as diabetes adults.

Compounds according to the invention are applicable not only in insulin-dependent diabetes mellitus type I, but also in diabetes type II, in which conventional drugs are ineffective to adequately reduce the level of blood sugar.

When type II diabetes high sugar level in the blood after a meal is retained significantly longer than in healthy persons, but the compounds and their pharmaceutically acceptable salts according to the invention is applicable also in case of diabetes type II.

Additionally, the compounds and their pharmaceutically acceptable salts according to the invention is applicable to treatment and/or prevention of obesity.

Compounds of the following formula (I-0) according to the invention is:

(in the formula, the symbols have the above values can be obtained, for example, according to the following method:

(in the formula L1and L2each represent a leaving group such as halogen. Other symbols have the above values.)

(Stage 1)

This stage is a process of interaction of the compound (1) with the compound (A)represented by the formula, R1-X5N, in the presence of a base to form compound (2).

L1and L2more specifically, who appoints, for example, halogen, such as fluorine, chlorine, bromine. L1and L2may be the same or different.

Connection (1) for use at this stage is, for example, 3,5-debtor-2-nitroaniline, 3,5-dichloro-2-nitroaniline, 3,5-dibromo-2-nitroaniline, 4-bromo-5-fluoro-2-nitroaniline, 4,5-debtor-2-nitroaniline.

The amount of compounds (A), which must be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (1).

The amount of base that should be used also varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents.

The Foundation, which should be used can be any base, contributing to the formation of compound (2) in the interaction of the compound (1) with R1-X5N at this stage, including, for example, sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine. When R1-X5N means the primary or secondary amine, then the base can not be used.

The solvent of the reaction, which should is used, may be inert solvent is not described specifically, as it does not react. Specifically, for example, it may be pyridine, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

The reaction temperature at this stage can usually be from 0 to 250°C, preferably from 0 to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 5 hours.

Thus obtained compound (2) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 2)

This stage is the process of obtaining compound (3) in the interaction of the compound (2)obtained at the preliminary stage 1, with the compound (A), which is the same as in stage 1, or others, in the presence of a base.

This stage may also be carried out as in stage 1, or in accordance with method stage 1 or combining it with an ordinary method.

(Stage 3)

This stage is the process of obtaining compound (4) recovery of the nitro group in soy is ininii (3), obtained at the preliminary stage 2.

For recovery at this stage is applicable to any method well izvestny specialists in this field. Recovery at this stage specifically provides, for example, catalytic reduction using hydrogen, formic acid, ammonium formate, hydrazine hydrate is added and palladium, platinum, Nickel catalyst recovery using hydrochloric acid, ammonium chloride and iron and restoration using methanol and chloride of tin.

The amount of reducing agent to be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 1 to 50 equivalents, preferably from 2 to 20 equivalents per one equivalent of the compound (3).

The solvent of the reaction, which should be used is not specifically described, as it does not react. The solvent is applicable here, for example, methanol, N,N-dimethylformamide, ethyl acetate, tetrahydrofuran, and their mixed solvents.

The reaction temperature and the reaction time is not specifically defined. When the reaction temperature from -10 to 100°or so, preferably from 0 to 50°With or about, the reaction can be carried out for 1-20 hours or, preferably 1-5 hours is in or near.

Thus obtained compound (4) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography, or without separation and purification.

(Stage 4)

This stage is the process of obtaining compound (1) interaction of the compound (4)obtained at the preliminary stage 3, with the compound (5).

Cyclization at this stage can be carried out by any method described in references (e.g., Synthesis, 2000, Vol.10, pp.1380-1390), or in accordance with it, or combining it with an ordinary method.

Compound (5), which should be used can be, for example, pyridinecarboxamide, pyrazinecarboxamide, 1H-pyrazole-3-carboxaldehyde.

The amount of coupling (5)which should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 3 equivalents.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent is applicable here, for example, nitrobenzene, methanol, tetrahydrofuran, N,N-dimethylformamide, toluene and mixtures of such solvents.

Temperature reactionin can be from 0° C to the boiling point of the solvent.

The reaction time may usually be from 0.1 to 72 hours, preferably from 0.1 to 24 hours.

Thus obtained compound (1) according to the invention can be isolated and purified by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography.

(Stage 5-1)

This stage is the process of obtaining a condensed product of the interaction of the compound (4)obtained in stage 3, with the compound (6).

The amidation at this stage can be carried out using a carboxylic acid or its reactive derivative to the compound (6) and compound (4).

The amount of compound (6) or its reactive derivative, which should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 3 equivalents.

"Reactive derivative" of compound (6) includes, for example, mixed acid anhydrides, active esters, active amides, and they can be obtained, for example, according to the method described in WO 098/05641.

In this reaction, when using the carboxylic acid compound (6), then the reaction is preferably carried out in the presence of a condensing agent, nab is emer, such as carbonyldiimidazole, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, diphenylphosphoryl, piperidinomethyl-triphenylphosphine, preferred carbonyldiimidazole.

Not specifically limited number of condensing agent, which should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 10 equivalents relative to the compound (6).

The reaction can be carried out usually in an inert solvent. The inert solvent includes, for example, tetrahydrofuran, N,N-dimethylformamide, 1,4-dioxane, benzene, toluene, methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, pyridine or a mixture of such solvents.

The reaction temperature may usually be from 0°C to the boiling point of the used solvent reaction.

The reaction time may usually be from 0.1 to 72 hours, preferably from 0.5 to 24 hours.

For moderate promotion the reaction is carried out in the presence of a base and promoter of condensation.

The base includes 4-dimethylaminopyridine, triethylamine.

The amount of base that should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 1 equivalent per one mole of the carboxylic acid or its reactive derivative to the compound (6).

The promoter of condenser and includes a hydrate of N-hydroxybenzotriazole, N-hydroxysuccinimide.

The amount of the condensation promoter, which must be used is usually from 1 to 100 equivalents, preferably 1 to 5 equivalents to one mole of the carboxylic acid or its reactive derivative to the compound (6).

In the reaction, when the amino group or aminogroups not involved in the reaction, the reactants, it is desirable that the amino group or aminogroups was adequately protected appropriately, then the reaction is carried out and the protective group is removed after the reaction.

Thus obtained condensation product may be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 5-2)

This stage is the process of obtaining the compound (I-0) by the cyclization condensation product obtained at the preliminary stage 5-1.

Cyclization at this stage can be carried out by any method described in references (for example, by the method described in Tetrahedron, 2001, Vol.57, No. 9, pp.1793-1800), or in accordance with it, or combining it with an ordinary method.

When p-toluensulfonate acid used in the cycle of the organization, then the number of p-toluensulfonate acid, which should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 1 equivalent.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent is applicable here, for example, toluene, N,N-dimethylformamide, 1,4-dioxane, N-organic and mixtures of such solvents.

The reaction temperature may usually be from 0 to 200°C, preferably from room temperature to the boiling point of the used solvent reaction.

The reaction time may usually be from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (I-0) according to the invention can be isolated and purified by any known method of isolation and purification, for example, concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography.

The compound (I-11) according to the invention can be also obtained according to the following method:

(in the formula L1and L2each represent a leaving group such as halogen. Other symbols have the above values.)

(Stage 6)

This stage is a process of interaction with the organisations (7) with the compound (a-1) in the presence of a base to form compound (8).

L1and L2more specifically means, for example, halogen, such as fluorine, chlorine, bromine.

The amount of compound (a-1), which is to be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (7).

The amount of base that should be used also varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents.

The Foundation, which should be used can be any base, contributing to the formation of compound (8) in the interaction of the compound (7) with the compound (a-1) at this stage, including, for example, sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine.

The solvent of the reaction, which should be used may be an inert solvent, is not described specifically, as it does not react. Specifically, for example, it may be pyridine, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

Temperature Rea is tion at this stage may be generally from 0° C to the boiling point of the used solvent for the reaction, preferably from 0 to 250°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.1 to 5 hours.

Thus obtained compound (8) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 7)

This stage is the process of obtaining compound (9) in the interaction of the compound (8) with the same compound (a-1), as at the preliminary stage 1, in the presence of a base.

This stage can be carried out as stage 6, or in accordance with method stage 1 or combining it with an ordinary method.

Thus obtained compound (9) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 8)

This stage is the process of obtaining compound (10) recovery nor is regroupe in connection (9).

This stage can be carried out as stage 3, or in accordance with it, or by combining it with an ordinary method.

Thus obtained compound (10) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 9)

This stage is the process of obtaining the compound (I-11) according to the invention by the interaction of the compound (10) with the above-mentioned compound (5) or (6).

The interaction of the compound (10) with compound (5) can be carried out as in stage 4, or in accordance with it, or combining it with an ordinary method.

The interaction of the compound (10) with compound (6) can be carried out as in stage 5-1 or 5-2, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (I-11) according to the invention can be isolated and purified by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

The compound (I-11) according to the invention can bittage obtained according to the following method:

(in the formula L1and L2each represent a leaving group such as halogen. Other symbols have the above values.)

(Stage 10)

This stage is a process of interaction of the compound (11) with the above-mentioned compound (a-1) before the formation of compounds (12).

This stage can be carried out as stage 6, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (12) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 11)

This stage is the process of obtaining compound (13) by the interaction of the compound (12) with the above-mentioned compound (a-1).

This stage can be carried out as stage 6, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (13) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction dissolve elem, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 12)

This stage is the process of obtaining compound (14) recovery of nitro group in the compound (13).

This stage can be carried out as stage 3, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (14) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 13)

This stage is the process of obtaining compound (15) with the introduction of the nitro group in the compound (14)obtained in the preliminary stage.

Nitration at this stage can be carried out by any method described in references (e.g., Synthetic Communication, 2001, Vol.31, No. 7, pp.1123-1128), or in accordance with it, or combining it with an ordinary method. If necessary, the nitration can be carried out after protecting the amino group of compound (14).

When potassium nitrate is used for the nitration, the amount of potassium nitrate, which should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 2 equivalent is allentow.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent is applicable here, for example, triperoxonane acid, anhydride triperoxonane acid, hydrochloric acid, sulfuric acid, nitric acid.

The reaction temperature may usually be from 0°C to the boiling point of the used solvent for the reaction, preferably from room temperature to 70°C.

The reaction time may usually be from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (15) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 14)

This stage is the process of obtaining compound (16) restoration of the nitro group in compound (15).

This stage can be carried out as stage 3, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (16) can be subjected to the next stage after separation and purification by any known means of separation and purification, the example of the concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 15)

This stage is the process of obtaining the compound (I-11) according to the invention by the interaction of the compound (16) with the above-mentioned compound (5) or (6).

The interaction of the compound (16) with compound (5) can be carried out as in stage 4, or in accordance with it, or by combining it with an ordinary method.

The interaction of the compound (16) with compound (6) can be carried out as in stage 5-1 or 5-2, or in accordance with it, or combining it with an ordinary method.

The compound (I-11) according to the invention can also be obtained by another method in which after connection (14) and (6) reacts in the reaction product enter the nitrogroup and at the end of the nitro-group is reduced to amino groups simultaneously with the cyclization of the resulting compound, or, if desirable, the connection separately subjected to cyclization.

The amidation of the compound (14) and compound (6), nitration, the restoration of the nitro group to the amino group and cyclization can be carried out as in stage 5-1, stage 13 stage 3 and stage 5-1, respectively, or in accordance with them, or join them in the usual way.

Thus obtained compounds is the (I-11) according to the invention can be isolated and purified by any known means of separation and purification, for example, concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

The compound (I-11-0) according to the invention can be also obtained according to the following method:

(in the formula L1L2L3and L4each represent a leaving group such as halogen. Rp1represents a hydroxy-protective group. Other symbols have the above values.)

(Stage 16)

This stage is a reaction of introducing a protective group into the compound (17). The introduction of protective group Rp1in the compound (17) at this stage can be carried out by any method described in references (for example, Protective Groups in Organic Synthesis, by T.W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method.

Rp1includes more concretely, for example, methoxymethyl, methyl, benzyl, 4-methoxybenzyl, 2-(trimethoxysilyl)ethoxymethyl, 2-(trimethylsilyl)ethyl, tert-butyldimethylsilyl, tert-butyl carbonyl.

The number of connections (), which should be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent is soedineniya (17).

The amount of base that should be used also varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents.

The Foundation, which should be used can be any base, contributing to the formation of compound (18) in the interaction of the compound (17) with the compound (C) at this stage, including, for example, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine, imidazole.

The reaction temperature may be generally from 0°C to the boiling point of the used solvent for the reaction, but preferably from 0 to 80°C.

The reaction time may be generally from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

The solvent of the reaction, which should be used may be an inert solvent, is not described specifically, as it does not react. Specifically, for example, it may be pyridine, toluene, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

Thus obtained compound (8) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration,concentration under reduced pressure, by solvent extraction, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 17)

This stage is a process of interaction of the compound (18) with the above-mentioned compound (a-1) to obtain compound (19).

This stage can be carried out as step 10, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (19) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 18)

This stage is the process of obtaining compound (20) restoration of the nitro group in the compound (19).

This stage can be carried out as stage 12, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (20) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without split and cleanup.

(Stage 19)

This stage is the process of obtaining compound (21) with the introduction of the nitro group in the compound (20).

This stage can be carried out as stage 13, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (21) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 20)

This stage is the process of obtaining compound (22) the restoration of the nitro group in the compound (21).

This stage can be carried out as stage 14, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (22) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 21)

This stage is the process of obtaining compound (23) in the interaction of the compound (22) with the above modifications is the group of (5) or (6).

The interaction of the compound (22) with compound (5) can be carried out as in stage 4, or in accordance with it, or combining it with an ordinary method.

The interaction of the compound (22) with compound (6) can be carried out as in stage 5-1 or 5-2, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (23) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 22)

This stage is the process of obtaining compound (24) by removing the hydroxy-protective group in the compound (23).

Removing the protective group at this stage can be carried out by any method described in references (for example, Protective Groups in Organic Synthesis, by T.W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method. When Rp1means benzyl, then the protective group may be removed, for example, catalytic hydrogenation with a catalyst of palladium on coal.

When using a catalyst of palladium hydroxide on coal to remove Rp1then the number is utilizator, which should be used can typically be from 0.1 to 1000 equivalents, preferably from 0.1 to 10 equivalents.

The solvent of the reaction, which must be used at this stage is not described specifically, as it does not react. The solvent here is applicable, for example, methanol, ethanol.

The reaction temperature may be generally from room temperature to the boiling point of the used solvent for the reaction, preferably from room temperature to 100°C.

The reaction time may be generally from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (24) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 23)

This stage is the process of obtaining the compound (I-2) according to the invention according to stage (stage 23-1) interaction of the compound (24) with compound (C) or according to stage (stage 23-2) interaction of the compound (24) with compound (D).

(Stage 23-1)

L4in connection (With) specifically means, for example, halogen, such as chlorine, bromine, iodine.

The number is unity (C), which should be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (24).

The reaction at this stage can be carried out in the presence of a base.

The amount of base that should be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (24).

The Foundation, which should be used can be any base, contributing to the formation of compound (I-2) in the interaction of the compound (24) with compound (C), including, for example, sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine.

The solvent of the reaction, which should be used may be an inert solvent, is not described specifically, as it does not react. Specifically, for example, it may be pyridine, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

The reaction temperature at this stage can usually be on the 0° C to the boiling point of the used solvent for the reaction, preferably from 0 to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 5 hours.

Thus obtained compound (I-2) according to the invention can be isolated and purified by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

(Stage 23-2)

This stage is the process of obtaining the compound (I-2) according to the invention in the interaction of the compound (24)obtained in the preliminary stage 24, with the compound (D) with the following optional introduction of protective groups and the removal of the protective group from the product.

The interaction of the compound (24) with compound (D) is the so-called Mitsunobu reaction, which may be carried out in the presence of phosphine compounds and azo compounds in accordance with the method described in references (for example, "The of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products", by O. Mitsunobu; Synthesis, Vol.1, 1981, pp.1-28), or in accordance with it, or combining it with an ordinary method.

The amount of coupling of the alcohol (D), which should be used at this stage can usually be from 0.5 to 10 equivalents, preferably from 1 to 3, e is bivalents on 1 equivalent of the compound (24).

Connection of phosphine, which is to be used, can usually be triphenylphosphine or triethylphosphine.

The amount of phosphine compounds, which should be used can usually be from 0.5 to 10 equivalents, preferably 1 to 3 equivalents to 1 equivalent of the compound (24).

Uzasadnienie, which should be used can be, for example, diethyl-azodicarboxylate, aminobutiramida-azodicarboxylate.

The number of compounds that must be used can usually be from 0.5 to 10 equivalents, preferably 1 to 3 equivalents to 1 equivalent of the compound (24).

The reaction time at this stage may be usually from 1 to 48 hours, preferably from 4 to 12 hours.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent for the reaction, preferably from 15 to 30°C.

The solvent of the reaction, which must be used at this stage is not described specifically, as it does not react. Specifically, for example, is applicable here tetrahydrofuran, toluene.

The compound (I-11-0) according to the invention can also be obtained by another method in which after interaction of compounds (20) and (6) in the reaction product enter the nitrogroup and at the end of the nitro-group is reduced to amino groups simultaneously with the cyclization on ochomogo connection or if desirable, the connection separately subjected to cyclization.

The amidation of the compound (20) and compound (6), nitration, the restoration of the nitro group to the amino group and cyclization can be carried out as in stage 5-1, stage 13 stage 3 and stage 5-1, respectively, or in accordance with them, or join them in the usual way.

Thus obtained compound (I-11-0) according to the invention can be isolated and purified by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

Of the compounds (I) according to the invention compound (I-4), where X denotes a nitrogen atom, can be obtained according to the following method:

(In these formulas, Rx represents C1-6alkyl having 2 Deputy from Halogens, aldehydes, esters, CN or their homologues, and other symbols have the above values.)

(Stage 24)

This stage is the process of obtaining compound (25) from compound (4).

This reaction can be carried out in the presence of a base in a manner described in references (for example, Indian J. Chem. Sect. B; 32; 2; 1993; 262-265), or in accordance with it, or combining it with an ordinary method.

For example, when the and the reaction is carried out using sulfur dioxide, the amount of sulfur dioxide that must be used can typically be from 0.1 to 500 equivalents, preferably from 0.5 to 10 equivalents.

The Foundation, which should be used can be any base, contributing to the formation of compound (25) in collaboration with compound (4), including, for example, sodium hydroxide, sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine.

The reaction time at this stage may be usually from 1 to 48 hours, preferably from 4 to 12 hours.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent for the reaction, but preferably from 0 to the boiling point.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. Specifically, for example, is applicable here ethanol, water, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

Thus obtained compound (25) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, Chris is alsatia, repeated precipitation, chromatography or without separation and purification.

(Stage 25)

This stage is the process of obtaining compound (26) from compound (25). When using hydrazine monohydrate, the reaction at this stage can be carried out by any method described in references (for example, Indian J. Chem. Sect. B; EN; 32; 2; 1993; 262-265), or in accordance with it, or combining it with an ordinary method.

The amount of hydrazine monohydrate, which is to be used, can usually be from 0.1 to 1000 equivalents, preferably 1 to 100 equivalents.

The reaction time at this stage may be usually from 1 to 48 hours, preferably from 4 to 24 hours.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent reaction.

Preferably the reaction at this stage is carried out in the absence of solvent, but a solvent may be used, as it does not react. To applicable solvents for the reaction include ethanol, water, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

Thus obtained compound (26) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentri what Finance under reduced pressure, by solvent extraction, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 26)

This stage is the process of obtaining the compound (I-4) according to the invention in the interaction of the compound (26) with compound (E).

This reaction can be carried out by any method described in references (for example, Indian J. Chem. Sect. B; EN; 32; 2; 1993; 262-265), or in accordance with it, or combining it with an ordinary method.

For example, when you create a pyrazole, it can be synthesized by reaction with tetramethoxypropane.

The number of tetramethoxypropane, which should be used can typically be from 0.1 to 500 equivalents, preferably from 0.5 to 100 equivalents.

The reaction time at this stage may be usually from 1 to 48 hours, preferably from 4 to 24 hours.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent reaction.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. Specifically, for example, is applicable here ethanol, water, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

Thus obtained compound (I-4) according to the invention can be isolated and PTS who placed any known method of separation and purification, for example, concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

Compounds of the following formula (I-12) according to the invention is:

(in the formula, the symbols have the above values) can also be obtained, for example, according to the following method:

(in the formula L1and L2each represent a leaving group such as halogen, and other symbols have the above values.)

(Stage 27)

This stage is a process of interaction of the compound (27) with the above-mentioned compound (a-1) in the presence of a base to form compound (28).

L1and L2more specifically means, for example, halogen, such as fluorine, chlorine, bromine.

The amount of compound (a-1), which is to be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (27).

The amount of base that should be used also varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, PR is doctitle from 0.5 to 5 equivalents.

The Foundation, which should be used can be any base, contributing to the formation of compound (28) in the interaction of the compound (27) with the compound (a-1) at this stage, including, for example, sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine.

The solvent of the reaction, which should be used may be an inert solvent, is not described specifically, as it does not react. Specifically, for example, it may be pyridine, toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, 1-methyl-2-pyrrolidinone.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent for the reaction, preferably from room temperature to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 5 hours.

Thus obtained compound (28) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 28)

This is adiya is the process of obtaining compound (29) the restoration of the nitro group in the compound (28), obtained at the preliminary stage.

For recovery at this stage is applicable to any method well-known to specialists in this field. Recovery at this stage specifically provides, for example, catalytic reduction using hydrogen, formic acid, ammonium formate, hydrazine hydrate is added and palladium, platinum, Nickel catalyst recovery using hydrochloric acid, ammonium chloride and iron and restoration using methanol and chloride of tin.

When using catalyst 10% palladium on coal for nitrogroup reduction, the amount of the catalyst is 10% palladium on coal, which should be used can typically be from 0.01 to 10 equivalents, preferably from 0.1 to 1 equivalent.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent here is applicable, for example, methanol, ethanol, tetrahydrofuran, N,N-dimethylformamide.

The reaction temperature may be generally from 0°C to the boiling point of the used solvent reaction.

The reaction time may be generally from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (29) can be subjected to the next stage after times the population and cleaning any known means of separation and purification, for example, concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 29)

This stage is the process of obtaining compound (30) with the introduction of the nitro group in the compound (29), obtained at the preliminary stage.

Nitration at this stage can be carried out after the optional protection of the aniline in a manner described in references (e.g., Synthetic Communication, 2001, Vol.31, No. 7, pp.1123-1128), or in accordance with it, or combining it with an ordinary method.

When potassium nitrate is used for the nitration, the amount of potassium nitrate, which should be used can typically be from 0.1 to 100 equivalents, preferably from 0.1 to 1 equivalent.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent is applicable here, for example, triperoxonane acid, anhydride triperoxonane acid, hydrochloric acid, sulfuric acid, nitric acid.

The reaction temperature may usually be from 0°C to the boiling point of the used solvent reaction.

The reaction time may usually be from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compounds is their (30) can be subjected to the next stage after separation and purification by any known means of separation and purification, for example, concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 30)

This stage is the process of obtaining compound (31) the recovery of the compound (30)obtained in the preliminary stage, with the above-mentioned compound (a-1).

This stage can be carried out after the optional protection aniline as well as on stage 27, or in accordance with it, or by combining it with an ordinary method.

Thus obtained compound (31) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 31)

This stage is the process of obtaining compound (32) the restoration of the nitro group in the compound (31), obtained at the preliminary stage 30.

The reaction at this stage can be carried out as in stage 8, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (32) can be subjected to the next stage after the separation and purification of any of the local method of separation and purification, for example, concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 32)

This stage is the process of obtaining the compound (I-2) according to the invention by the interaction of the compound (32), obtained at the preliminary stage, with the compound (5).

The reaction at this stage can be carried out as in stage 4, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (I-2) can be isolated and purified by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography.

(Stage 33-1)

This stage is the process of obtaining a condensed product of the interaction of the compound (32), obtained at the preliminary stage 31, with compound (6).

The reaction at this stage can be carried out as in stage 5-1, or in accordance with it, or combining it with an ordinary method.

Thus obtained condensation product may be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, what koncentrirovannaya under reduced pressure, crystallization, extraction with solvent, re-precipitation, chromatography or without separation and purification.

(Stage 33-2)

This stage is the process of obtaining the compound (I-12) the cyclization product condensable obtained at the preliminary stage 33-1.

Cyclization at this stage can be carried out as in stage 5-2, or in accordance with it, or combining it with an ordinary method.

The compound (I-11) according to the invention can also be obtained by another method in which after connection (29) and (6) reacts in the reaction product enter the nitrogroup and at the end of the nitro-group is reduced to amino groups simultaneously with the cyclization of the resulting compound, or, if desirable, the connection separately subjected to cyclization, or after cyclization or before the cyclization of the compound is subjected to reaction with compound (A).

The amidation of the compound (29) and the compound (6), nitration, the restoration of the nitro group to the amino group, the reaction with compound (a) and cyclization can be carried out as in stage 5-1, stage 13, stage 3, stage 30 stage and 5-1, respectively, or in accordance with them, or join them in the usual way.

Thus obtained compound (I-12) according to the invention can be separated and purified by any known means of separation and purification, nab the emer concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

The compound (I-12) according to the invention can also be obtained from compound (31), which is obtained according to the following method:

(in the formula, the symbols have the above values.)

(Stage 34)

This stage is the process of obtaining compound (34) by the interaction of the compound (33) with the above-mentioned compound (a-1). The reaction at this stage can be carried out as in stage 27, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (34) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 35)

This stage is the process of obtaining compound (35) by the interaction of the compound (34) with the above-mentioned compound (a-1). The reaction at this stage can be carried out as in stage 30, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (35) can be subjected to etousa stage after separation and purification by any known means of separation and purification, for example, concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification.

(Stage 33-1)

This stage is the process of obtaining compound (31) by turning-C(O)OR8in the compound (35)obtained at the preliminary stage, the amino group, for example, by the so-called reactions of kurzius. The reaction at this stage can be carried out as in stage 48, which will be described hereafter, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (31) can be isolated and purified by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography.

Using the thus obtained compound (31), in accordance with the process of the above stages 31, 32, 33-1 or 33-2 can be obtained compound (I-12) according to the invention.

The compound (I-31) according to the invention can be also obtained according to the following method:

(in the formulas, n is 1 or 2, Y represents a leaving group, and other symbols have the above values.)

(Stage 36)

This stage what is the process for obtaining compounds (37) the interaction of the compound (27) with compound (36) in the presence of a base and a metal catalyst.

L1and L2more specifically means, for example, halogen, such as fluorine, chlorine, bromine.

M1can be a substance that promotes the formation of compound (37) the interaction of the compound (27) with compound (36). Specifically, for example, it may be triamcinolona, baronova acid, boronate. More specifically, the compound (36) includes, for example, trimethyl-(pyridin-2-yl)tin or 1-(tert-butoxycarbonyl)pyrrol-2-Bronevoy acid.

In the case when the compound (36) using trimethyl-(pyridin-2-yl)tin, for example, the reaction may be so-called Stille reaction.

In the case when the compound (36) using 1-(tert-butoxycarbonyl)pyrrol-2-Bronevoy acid, for example, the reaction may be so-called Suzuki reaction.

The amount of compound (36)that should be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 50 equivalents, preferably from 0.2 to 10 equivalents to one equivalent of the compound (27).

The amount of base that should be used also varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents.

The reason that due is to be used, can be any base, contributing to the formation of compound (37) in the interaction of the compound (27) with compound (36) at this stage, including, for example, sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-butyrate, potassium, triethylamine.

The amount of the metal catalyst to be used is also changed depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.01 to 10 equivalents, preferably from 0.05 to 5 equivalents.

The metal catalyst to be used may be any that is conducive to the formation of compound (37) in the interaction of the compound (27) with compound (36) at this stage, including, for example, tetranitroaniline palladium, dichlorobistriphenylphosphine palladium, dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent is applicable here, for example, dimethyl simple ether of ethylene glycol, water, toluene, tetrahydrofuran, N,N-dimethylformamide, 1,4-dioxane, benzene, acetone.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent is eacli, preferably from room temperature to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (37) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 37)

This stage is the process of obtaining compound (38) the interaction of the compound (37) with the above-mentioned compound (a-1).

The reaction at this stage can be carried out as in stage 27, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (38) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 38)

This stage is the process of obtaining compound (39) restoration of the heteroaromatic ring and the nitro group in the compound (38) with metal catalysts of the om in the atmosphere of hydrogen and optionally, the introduction of the protective group in the reaction product.

The amount of reductant that should be used can typically be from 0.01 to 10 equivalents, preferably from 0.1 to 1 equivalent.

The reducing agent to be used may be any that is conducive to the formation of compound (39) from the compound (38) at this stage. As a reducing agent applies here, for example, 10% palladium on coal or platinum black.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent here is applicable, for example, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, ethyl acetate.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent for the reaction, preferably from room temperature to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

The pressure of the reaction at this stage may be generally from normal pressure to 100 atmospheres, preferably from normal pressure to 20 ATM.

Thus obtained compound (39) can be subjected to the next stage after separation and purification by any known means of separation and purification, for example, concentri what Finance, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 39)

This stage is the process of obtaining compound (40) with the introduction of the nitro group in the compound (39). The reaction at this stage can be carried out as in stage 29, or in accordance with it, or combining it with an ordinary method. If desirable, Rp1can be converted.

Thus obtained compound (40) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 40)

This stage is the process of obtaining compound (41) the restoration of the nitro group in the compound (40). The reaction at this stage can be carried out as in stage 31, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (41) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, krystallis what tion, by solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 41)

This stage is the process of obtaining compound (42) in the interaction of the compound (41) with the above-mentioned compound (5) or in the interaction of the compound (41) with the above-mentioned compound (6) with subsequent cyclization of the resulting product.

The interaction of the compound (41) with compound (5) can be carried out as in stage 32, or in accordance with it, or combining it with an ordinary method.

The interaction of the compound (41) with compound (6) can be conducted as well as on stages 33-1 and 33-2, or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (42) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 42)

This stage is the process of obtaining compound (43) removing the amino-protective group Rp1in the obtained compound (42).

The removal of the protective group Rp1can be performed as in the method described in references (for example, Protective Groups in Organic Synthesis, by .W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (43) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 43)

This stage is the process of obtaining the compound (I-3) according to the invention in the interaction of the compound (43) with compound (F). The introduction of the amino-protective group, R4at this stage can be carried out just as in the method described in references (for example, Protective Groups in Organic Synthesis, by T.W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method.

More specifically, R4means alkyl, alkylamide, carbarnoyl, allylcarbamate, alkyl carbamate.

The compound (F) includes specifically, for example, acetic anhydride, triperoxonane anhydride, propionic acid, Chloroacetic acid, acrylate, methansulfonate, benzylchloride.

The amount of compound (F), which should be used depends on the type of connection and the used solvent and other reaction conditions, but usually can be hot,1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (43).

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. It is, for example, is applicable here dichloromethane, chloroform, tetrahydrofuran, acetonitrile, dimethylformamide, benzene, acetone, ethanol, 2-propanol.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent for the reaction, preferably from room temperature to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

The compound (I-31) according to the invention can also be obtained by another method in which after interaction of compounds (39) and (6) in the product enter the nitrogroup and at the end of the nitro-group is reduced to amino groups simultaneously with the cyclization of the resulting compound, or, if desirable, the connection separately subjected to cyclization.

The amidation of the compound (39) and the compound (6), nitration, the restoration of the nitro group to the amino group and cyclization can be carried out as in stage 5-1, stage 13 stage 3 and stage 5-1, respectively, or in accordance with them, or join them in the usual way.

Thus obtained compound (I-31) from which briteney can be separated and purified by any known means of separation and purification, for example, concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography.

When the amino-protective group Rp1in the compound (42) corresponds to the desired R4, then the subsequent stage 42 and 43 are not necessary, i.e. the compound (42) can be directly connection according to the invention.

When the compound (43) is the desired connection, then stage 43 is not necessary, i.e. the compound (43) can be directly connection according to the invention.

The compound (I-31) according to the invention can be also obtained according to the following method:

(in the formula Rp2Rp3Rp4each represent a protective group, L represents a leaving group, and other symbols have the above values.)

(Stage 44)

This stage is the process of obtaining compound (45) in the interaction of the compound (44) with the above-mentioned compound (36). Rp2is X51-protective group, concretely including, for example, such as methoxymethyl, methyl, benzyl, 4-methoxy-benzyl, 2-(trimethylsilyl)ethoxymethyl, 2-(trimethylsilyl)ethyl, tert-butyldimethylsilyl, tert-butylcarbamoyl. Rp3is carboxyl-protective group, specifically including the I, for example, such as methyl, ethyl, tert-butyl, benzyl, 4-methoxy-benzyl, 2-(trimethylsilyl)ethyl, tert-butyldimethylsilyl. Rp4is inert accelgroup, specifically including, for example, methyl, ethyl, tert-butyl, benzyl, 4-methoxy-benzyl, 2-(trimethylsilyl)ethyl. The interaction at this stage can be carried out as in stage 36, or in accordance with it, or combining it with an ordinary method. Thus obtained compound (45) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 45)

This stage is the process of obtaining compound (46) the restoration of the heteroaromatic ring compound (45)obtained at the preliminary stage, with a metal catalyst in a hydrogen atmosphere.

The amount of reductant that should be used can typically be from 0.01 to 10 equivalents, preferably from 0.05 to 1 equivalent.

The reducing agent to be used may be any that is conducive to the formation of compound (46) from the compound (45) at this stage. As the reductant apply here is, for example, 10% palladium on coal or platinum black.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent here is applicable, for example, methanol, ethanol, tetrahydrofuran, N,N-dimethylformamide, 1,4-dioxane, ethyl acetate.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent for the reaction, preferably from room temperature to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

The pressure of the reaction at this stage may be generally from normal pressure to 100 atmospheres, preferably from normal pressure to 20 ATM.

Thus obtained compound (46) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 46)

This stage is the process of obtaining compound (47) by removing the protective group Rp2in the compound (46). Removing the protective group at this stage can be carried out in the manner described the links (for example, Protective Groups in Organic Synthesis, by T.W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method. When Rp2is methoxymethyl, then removing the protective group can be carried out, for example, using triperoxonane acid.

When used triperoxonane acid to remove Rp1then the amount of catalyst to be used can typically be from 0.01 to 1000 equivalents, preferably from 0.1 to 10 equivalents.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. The solvent here is applicable, for example, chloroform.

The reaction temperature may be generally from room temperature to the boiling point of the used solvent for the reaction, preferably from room temperature to 100°C.

The reaction time may be generally from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (47) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and PTS is tough. If desirable, Rp1can be converted.

(Stage 47)

This stage is the process of obtaining compound (48) the interaction of the compound (47) with compound (G). L represents a leaving group and may be the same as above L1and L2. Compound (G) specifically includes, for example, benzyl bromide, 4-fluoro-benzonitrile, 4-fluoro-benzaldehyde. The reaction at this stage can be carried out as in stage 27, or in accordance with it, or by combining it with an ordinary method. Thus obtained compound (48) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 48)

This stage is the process of obtaining compound (49) removing carboxyl-protective group Rp3in the compound (48). Carboxyl-protective group in the compound (48) can be any capable of acting as a protective group for carboxyl in the preliminary stages 44-47 and easily removed at stage 48. For example, it includes linear or branched lower alkyl, such as methyl, ethyl, tert-butyl; lower halogenated, such as 2-iodomethyl, 2,2,2-trichlo is ethyl; lower alkenyl, such as allyl, 2-propenyl, 2-methyl-2-propenyl, and aralkyl, such as benzyl, p-methoxybenzyl.

Insertion and removal of carboxyl-protective group Rp3can be carried out by any method described in references (for example, Protective Groups in Organic Synthesis, by T.W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method.

Thus obtained compound (49) can be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, extraction with solvent, crystallization, re-precipitation, chromatography or without separation and purification. If desirable, Rp1can be converted.

(Stage 49)

This stage is the process of obtaining compound (50) in the interaction of the compound (49) with the compound (H), and, for example, the so-called reaction turning kurzius. Using the azide compound of phosphoric acid and an alcohol compound (17-1) in the presence of base, the reaction can be carried out by any method described in references (for example, Tetrahedron, Vol.31, 1974, pp.2151-2157), or in accordance with it, or combining it with an ordinary method.

The amount of alcohol compounds alcohol (N), which should be used ismene the Xia depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents to one equivalent of the compound (49).

The amount of base that should be used varies depending on the connection type and the used solvent and other reaction conditions, but can be generally from 0.1 to 20 equivalents, preferably from 0.5 to 5 equivalents.

The azide compound of phosphoric acid can be any conducive to the formation of compound (50) in the interaction of the compound (49) with the compound (H) at this stage. For example, it may be azide diethylphosphinic acid, azide diphenylphosphinic acid.

The Foundation, which should be used can be any base, contributing to the formation of compound (50) in the interaction of the compound (49) with the compound (H) at this stage. For example, it may be sodium hydride, cesium carbonate, sodium carbonate, potassium carbonate, potassium phosphate, potassium acetate, tert-piperonyl potassium, triethylamine.

The solvent of the reaction, which must be used at this stage, not specifically described, as it does not react. For example, it may be toluene, tetrahydrofuran, methylene chloride, chloroform, 1,4-dioxane, benzene.

The reaction temperature at this stage may be generally from 0°C to the boiling point of the used solvent Rea the tion, preferably from room temperature to 150°C.

The reaction time at this stage may be usually from 0.1 to 72 hours, preferably from 0.5 to 12 hours.

Thus obtained compound (50) may be subjected to the next stage after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography or without separation and purification.

(Stage 50)

This stage is the process of obtaining compound (40) with the introduction of the nitro group in the compound (50). The reaction at this stage can be carried out as in stage 29, or in accordance with it, or combining it with an ordinary method.

Without separation and purification or after separation and purification by any known means of separation and purification such as concentration, concentration under reduced pressure, crystallization, solvent extraction, re-precipitation, chromatography, thus obtained compound (40) can be processed in accordance with the above stages 40-43 to obtain thereby the compound (I-3) according to the invention.

The compound (I-31) according to the invention can also be obtained by another method in which after Rp4remove from the soedineniya (50) with the formation of a derivative of aniline and then the derivative of aniline is subjected to interaction with compound (6), in the reaction product enter the nitrogroup and restore to last amino simultaneously with the cyclization of the resulting compound, or, if desirable, the connection separately subjected to cyclization.

The amidation of the compound (50) and the compound (6), nitration, the restoration of the nitro group to the amino group and cyclization can be carried out as in stage 5-1, stage 13 stage 3 and stage 5-1, respectively, or in accordance with them or join them in the usual way. Remove Rp4can be carried out in the same manner as the above method (Protective Groups in Organic Synthesis, by T.W. Green, 2ndEd., John Wiley & Sons, 1991), or in accordance with it, or combining it with an ordinary method.

New 2-heteroaryl-substituted benzimidazole derivatives according to the invention can be in the form of their pharmaceutically acceptable salts. Salts can be obtained by any conventional method, compound (I-0) according to the invention and of the compounds of the above formulas (I-1), (I-11), (I-12), (I-2), (I-11-0), (I-31) and (I-4), all of them are among the compounds (I-0).

Specifically, when the compound (I-0), (I-1), (I-11), (I-12), (I-2), (I-11-0), (I-31) and (I-4) are a group of basic character, obtained, for example, from amino or pyridium, in the molecule, then the compounds may be treated with acid in order to convert them into the corresponding pharmaceutically acceptable salt.

p> Additive salts with acids include, for example, hydrogenogenic, such as hydrochloride, hydrohloride, hydrobromide, hydroiodide; salts with inorganic acids such as nitrates, perchlorates, sulfates, phosphates, carbonates; lower alkyl sulphonates, such as methanesulfonate, triftoratsetata, econsultancy; arylsulfonate, such as benzosulfimide, p-toluensulfonate; salts with organic acids, such as fumarate, succinate, citrates, tartratami, oxalates, maleate; other additive salts with organic acids, amino acids, such as glutamate, aspartate. When the compounds according to the invention have an acid group in the molecule, for example, when they have a carboxyl group, then the compounds may be processed by the base in order to turn them into the corresponding pharmaceutically acceptable salt. Additive salts with bases include, for example, alkali metal salts with sodium or potassium; salts of alkaline-earth metals with calcium or magnesium; ammonium salts; additive salts with organic bases with guanidine, triethylamine, dicyclohexylamine, etc. In addition, the compounds according to the invention can also be in any other form of hydrate or solvate their free compounds or their salts.

In the production of pharmaceuticals for the prophylaxis and treatment is of type II diabetes or related diseases or symptoms of the compounds of formula (I) according to the invention can be combined with substances, with the function of the media.

The dose of the compounds of formula (I) according to the invention for the prevention or treatment of disease course varies depending on the characteristics of symptoms requiring treatment of the patient, the particular compound selected for this, and route of administration.

In addition, the dose varies depending on age, body weight and sensitivity of patients. As a rule, the daily dose for single or multiple injection can be from about 0.001 mg/kg body weight to about 100 mg/kg body weight, preferably from about 0.01 mg/kg body weight to about 500 mg/kg body weight, more preferably from about 0.1 mg/kg body weight to about 10 mg/kg of body weight. There may be times when you may need a dose higher range.

An example of a suitable doses for oral administration are described below. Daily dose for single or two - to four injection may be at least from about 0.01 mg to at most to 2.0, Preferably the frequency of the introduction of a day - once or twice a day, and the daily dose is from about 1.0 mg to about 200 mg, More preferably the daily dose is from about 10 mg to about 100 mg for administration once a day.

For intravenous or oral administration of a typical dose of compound (I) can be from about 0.001 mg/kg body weight suck is up to about 100 mg/kg of body weight per day (preferably from about 0.01 mg/kg of body weight per day to about 10 mg/kg of body weight per day), more preferably from about 0.1 mg/kg of body weight per day to about 10 mg/kg of body weight per day.

As mentioned here above, the pharmaceutical composition according to the invention contains a compound of the formula (I) and a pharmaceutically acceptable carrier. The term "composition" means that it contains not only the product obtained directly or not directly by Association, by hybridization or by aggregation of two or more of any ingredients, the product resulting from dissociation of one or more ingredients, or compound resulting from the reaction or interaction of different types of ingredients, but also the active and inactive ingredients that make up the media pharmaceutically acceptable carrier).

The combination with a pharmaceutically acceptable carrier, the composition according to the invention preferably contains a compound of the formula (I) in an amount effective for the treatment and prevention of type II diabetes and to delay onset of the disease.

To Institute an effective dose of the compounds according to the invention is a mammal, particularly humans, is applicable to any suitable route of administration. For example, oral administration, rectal administration, local injection, intravenous, ophthalmic introduction, introduction through the lungs or nasal administration. Examples of forms for administration include tablets, pills, powders, suspensions, solutions, capsules, creams, aerosols. The preferred tablet for oral administration.

When preparing the compositions for oral administration are applicable to any conventional pharmaceutical environment. Her examples are water, glycol, oil alcohol, flavouring agents, preservatives, dyes. In the preparation of liquid compositions for oral administration, for example, mentioned suspensions, elixirs and solutions. Their carriers are, for example, starch, sugar, microcrystalline cellulose, diluent, the promoter granulation, lubricant, binder, disintegrity agent. In the preparation of solid compositions for oral administration, for example, the above-mentioned powders, capsules and tablets. Mainly preferred such solid compositions for oral administration.

Because of the ease of their administration tablets and capsules are the most convenient forms for oral administration. If desired, tablets may be coated according to standard techniques aqueous and non-aqueous coating.

In addition to these traditional ways of their introduction to the compounds of formula (I) can be also introduced in systems with controlled release and/or systems with controlled delivery, for example, as in U.S. patents 3845770, 3916899, 3563809, 3598123, 3630200 and 4008719.

The pharmaceutical composition of p the invention, suitable for oral administration include capsules, pills and tablets, which contain a predetermined amount of the active ingredient in the form of powder or granules or in the form of water-soluble liquids, water-insoluble liquids, emulsions of the type oil-in-water or emulsions water in oil. Such compositions can be prepared by any pharmaceutical methods, and all methods include the process of combining the active ingredient with a carrier of one or more necessary ingredients.

Typically, the active ingredient evenly and completely mixed with the liquid medium, or well-divided solid carrier, or both and then, if desirable, the product give a suitable form, to obtain the composition. For example, the tablets obtained by compressing and molding, optionally along with one or more additional components. Using the appropriate machine pressed tablets can be obtained by mixing the active ingredient, optionally, with a binder, lubricant, inert carrier, a surface-active agent or a dispersant, and pressing the mixture in any desired manner in powder or granules.

Molded tablets are produced by forming a mixture of powdered wet compound and an inert liquid rabbanites is using the appropriate machine.

Preferably, each tablet contains from about 1 mg to 1 g of the active ingredient, and a wafer and capsules, each contain from about 1 mg to 500 mg of active ingredient.

Examples of forms for administration of the compounds of formula (I) for pharmaceutical applications are as follows:

Table 1

Suspension for injection (I.M.)
mg/ml
the compound of formula (I)10
the methylcellulose5,0
Tween 800,5
benzyl alcohol : 9,0
the benzalkonium chloride1,0

water for injection is added to 1.0 ml

Table 2

Tablets
mg tablet
the compound of formula (I)25
the methylcellulose415
Tween 8014,0
benzyl alcohol : 43,5
magnesium stearate2,5

500 mg

Table 3

Capsules
mg/caps the La
the compound of formula (I)25
the lactose powder573,5
magnesium stearate1,5

only 600 mg

Table 4

Aerosol
one container
the compound of formula (I)24 mg
lecithin, NF Liq. Conc.1.2 mg
Trichlorofluoromethane, NF4,025 g
DICHLORODIFLUOROMETHANE, NF12,15 g

The compounds of formula (I) can be used in combination with other drugs, is applicable not only for illnesses and symptoms associated with type II diabetes, but also for the treatment/prevention/delay of type II diabetes. Additional medicines may be introduced by any route of administration and dose commonly used in medicine, simultaneously with the compound of the formula (I) or separately.

When the compound of formula (I) are used along with one or more other drugs, then the preferred pharmaceutical composition containing the compound of formula (I) and complementary medicines. Accordingly, the pharmaceutical composition according to the invention can content is to be not only the compound of formula (I), but also one or more of these active ingredients. Examples of active ingredients that can be combined with compounds of formula (I), cited below, which, however, are not restrictive. They can be introduced separately or can be entered simultaneously as contained in the same pharmaceutical composition.

(a) bis-guandi (for example, buformin, Metformin, phenformin),

(b) PPAR agonists (for example, troglitazone, pioglitazone, rosiglitazone),

(C) insulin,

(d) somatostatin,

(e) inhibitors α-glucosidase (e.g., voglibose, miglitol, acarbose),

(f) the promoters of insulin secretion (for example, acetohexamide, carbutamide, hlorpropamid, elgibali, gliclazide, glimmered, glipizide, gliadin, glisoxepide, gliburid, glyhexamide, pipename, fenbutatin, trashed, tolbutamide, tolciclate, nateglinide, Repaglinide) and

(g) inhibitors of DPP-IV (dipeptidyl-peptidases IV).

The mass ratio of the compounds of formula (I) to the second active ingredient may vary within wide limits and depends on the effective number of separate active ingredients. Accordingly, for example, when the compound of formula (I) combine with a PPAR agonist, then the mass ratio of the compounds of formula (I) to the PPAR agonist may be usually from about 1000/1 to 1/1000, preferably from about 200/1 to 1/200. The combination of compounds is Oia formula (I) and the other active ingredient may be in a wide range.

The efficiency of activation of glucokinase compounds of formula (I) according to the invention and the method of testing described below.

Excellent activates glucokinase action of the compounds of formula (I) can be determined by the method described in references (for example, Diabetes, Vol.45, pp.1671-1677, 1996), or in accordance with it.

The activity of glucokinase cannot be determined directly by measuring glucose-6-phosphate, but may be measured by the levels of Thio-NADH, which is formed when the enzyme-reporter, namely dehydrogenase glucose-6-phosphate, produces phosphogluconolactonase of glucose-6-phosphate, and on the basis of its content can be determined by the degree of glucokinase test connection.

This analysis was used recombinant GK human liver, which was expressiona E.coli as FLAG fused protein and purified by gel ANTIFLAG M2 AFFINITY GEL (Sigma).

Using 96-well plate, the analysis was carried out at 30°S. 69 μl of buffer for analysis (25 mm Hepes buffer/pH to 7.2, 2 mm MgCl2, 1 mm ATP, 0.5 mm TNAD, 1 mm dithiothreitol) was placed on the tablet and add to it 1 mm solution in DMSO connection one or DMSO as a control. Then add 20 ál of enzyme mixture (FLAG-GK, 20 units/ml G6PDH), cooled in ice, and to this was added 10 μl of substrate, 25 mm glucose, and initiated the reaction (final concentration of 25 mm glucose).

P is after the start of the reaction was measured by optical density at a wavelength of 405 nm for 10 minutes at intervals of 30 seconds and increase it for the first 5 minutes was used for the evaluation of the tested compounds. FLAG-GK was added so that the increase in optical density after 5 minutes in the presence of 1% DMSO was from 0.05 to 1.0.

The level OD control DMSO was taken as 100% and the level OD of the test compounds was determined at various concentrations. The level of OD at each concentration was calculated on a computer Emax (%) and ES (μm) and used as a performance indicator GK-activating connection.

Efficiency GK-activating compounds according to the invention was measured according to the method mentioned above, and the results are presented in table 1 below.

Table 5

(Efficiency GK-activating compounds according to the invention)
Connection # Emax (%)AS (µm)
Example 678321,4
Example 267682,3
Example 1226641,9

As shown in table 1 above, the compounds according to the invention have excellent efficiency GK-activating shown Emax and ES.

EXAMPLES

The invention is described more specifically with reference to the following examples, which, however, the invention should not limited to.

Sample preparation 1:

10 parts of the compound of example preparation 1 15 parts of a non-dusting of magnesium oxide and 75 parts of lactose uniformly mixed, to obtain a powdered drug or particle size of at most 350 μm. The drug encapsulation to obtain capsules.

Example of preparation 2:

45 parts of the compound of example preparation 1, 15 parts of starch, 16 parts of lactose, 21 parts of crystalline cellulose, 3 parts of polyvinyl alcohol and 30 parts of distilled water are uniformly mixed, and then crushed, granularit and dried and then sieved to obtain granules having a size of from 1410 to 177 μm in diameter.

Example preparation of 3:

Granules are produced in the same manner as in example of preparation 2. 3 parts of calcium stearate is added to 96 parts of pellets and molded under pressure, to obtain tablets having a diameter of 10 mm

Example preparation of 4:

10 parts of crystalline cellulose and 3 parts of calcium stearate is added to 90 parts of the granules obtained according to the method of sample preparation 2, and molded under pressure, to obtain tablets having a diameter of 8 mm covered with a slurry mixture generowania syrup and precipitated calcium carbonate, to obtain coated with sugar pills.

Hereinafter the invention is described more specifically with reference to preparation examples, examples of obtaining and comparative examples, which, however, the invention should not limited to.

In the thin layer of chromatography is in the examples, the silica gel 60F 245(Merck) was used for plates and UV detector was used for detection. As silica gel for the column used Wakogel C-300 (Wako Pure Chemical)), and as the silica gel for the column with reversed phase used LC-SORB(SP-B-ODS (Chemco)or YMC-GEL ODS-AQ 120-S50 (Yamamura Chemical Laboratory)).

The values of the abbreviations in the following examples is shown below.

i-Bu: isobutyl

n-Bu: n-butyl

t-Bu: tert-butyl

Me: methyl

Et: ethyl

Ph: phenyl

i-Pr: isopropyl

n-Pr: n-propyl

CDCl3: heavy chloroform

CD3OD: heavy methanol

DMSO-d6: heavy dimethyl sulfoxide

The values of the abbreviations in the following spectra nuclear magnetic resonance is shown below.

s: singlet

d: doublet

dd: double doublet

t: triplet

m: multiplet

br: broad

q: Quartet

J: constant interaction

Hz: Hertz

Example 1:

2-Pyridin-2-yl-5,6-bis(pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 3-(2-fluoro-4-nitro-phenoxy)pyridine:

2,09 g 3-hydroxypyridine and 5,52 g of potassium carbonate are added to a solution in dimethylformamide (20 ml) 3,18 g of 3,4-deformirovannoe and the reaction liquid was stirred at 90°C for 1 hour. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and obtained the STATCOM purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1), getting listed at the beginning of the connection.

(Stage 2) Obtain 5-fluoro-2-nitro-4-(pyridine-3-yloxy)-phenylamine:

1.0 g of the catalyst of 20% palladium hydroxide on coal are added to a solution in methanol (30 ml) 4,72 g 3-(2-fluoro-4-nitro-phenoxy)of pyridine and the reaction liquid is stirred in hydrogen atmosphere for 5 hours. The catalyst was removed by filtration and the solvent is evaporated under reduced pressure to give crude product. 1.88 g of potassium nitrate are added to a solution in triperoxonane acid (40 ml) of the obtained crude product, and the reaction liquid was stirred overnight at room temperature. Then the solvent is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution and saturated salt solution and then dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=4/1)to give specified in the header of the connection.

(Stage 3) Obtaining 4,5-bis(pyridine-3-yloxy)benzene-1,2-diamine:

285 mg of 3-hydroxypyridine and 829 mg of potassium carbonate are added to a solution in dimethylformamide (8 ml) 680 mg of 3-(2-fluoro-4-nitro-phenoxy)of pyridine and the reaction liquid was stirred at 90°C for 2 hours. The reaction of the LM is bone diluted with ethyl acetate, washed with water and saturated salt solution and then dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate)to give the crude product. 500 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in ethanol (10 ml) of the obtained crude product, and the reaction liquid is stirred in hydrogen atmosphere for 2 hours. The catalyst was removed by filtration and the solvent is evaporated under reduced pressure, obtaining specified in the header of the connection.

(Stage 4) to Obtain 2-pyridin-2-yl-5,6-bis(pyridine-3-yloxy)-1H-benzimidazole

0.01 ml pyridine-2-carboxaldehyde added to the solution in nitrobenzene (0.3 ml) 30 mg of 4,5-bis(pyridine-3-yloxy)benzene-1,2-diamine at 120°C and the reaction liquid was stirred at the same temperature for 2 hours. The reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is evaporated under reduced pressure and purify it, separated by thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1)to give specified in the title compound in the form of mass the East of the yellow substance.

1H NMR (CDCl3) δ: 7,10-7,40 (4H, m), 7,28 (1H, s), 7,38 (1H, DDD, J=1.2 Hz, 4.8 Hz and 7.6 Hz), a 7.62 (1H, s), 7,87 (1H, TD, J=7,6 Hz, 1.2 Hz), 8,12-to 8.40 (4H, m), scored 8.38 (1H, d, J=7,6 Hz), 8,63 (1H, d, J=4,8 Hz), and 10.8 (1H, users)

ESI-MS (m/e): 382 [M+H]

Example 2:

5-(2-Hydroxymethyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 1 or in accordance with the method or by combining with an ordinary method but using 5-fluoro-2-nitro-4-(pyridine-3-yloxy)phenylamine obtained in example 1 (stage 2), and 2-hydroxymethyl-phenol.

1H NMR (CDCl3) δ: of 4.45 (2H, s)6,76 (1H, d, J=8.0 Hz),? 7.04 baby mortality (1H, t, J=6.8 Hz), 7,08-7,30 (5H, m), 7,30-the 7.43 (2H, m), 7,86 (1H, TD, J=8.0 Hz, 2.4 Hz), 8,18-8,32 (1H, m), by 8.22 (1H, s), of 7.36 (1H, d, J=7,6 Hz), 8,62 (1H, d, J=8,4 Hz), 10,54 (1H, users)

ESI-MS (m/e): 411[M+H]

Example 3:

5-(2-(1-Hydroxy-ethyl)phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 2-(1-hydroxy-ethyl)phenol.

1H NMR (CDCl3) δ: of 1.25 to 1.34 (6H, m), 4.80 to 4,96 (1H, m), 7,76 (1H, DD, J=4.4 Hz, 8.0 Hz), 7,02-7,34 (6H, m), 7,38 (1H, t, J=6.4 Hz), 7,42-of 7.60 (1H, m), 7,87 (1H, TD, J=7,6 Hz, 1.6 Hz), 8,20-to 8.34 (2H, m), 8,39 (1H, d, J=7,6 Hz), 8,60-8,64 (1H, m), of 10.72 (1H, users)

ESI-MS (m/e): 425[MH]

Example 4:

5-(2-Acetyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 2-acetyl-phenol.

1H NMR (CDCl3) δ: 2,22-of 2.50 (3H, m), for 6.81 (1H, d, J=8,4 Hz), 7,00 was 7.45 (4H, m), 7,45-of 7.95 (5H, m), 8,20-8,35 (2H, m), of 8.37 (1H, d, J=7,6 Hz), 8,60-to 8.70 (1H, m), 10,49 (1H, users)

ESI-MS (m/e): 423[M+H]

Example 5:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 2-hydroxy-benzonitrile.

1H NMR (CDCl3) δ: to 6.80 (1H, t, J=8.0 Hz), 7,06 (1H, t, J=7,6 Hz), 7,25-to 7.35 (2H, m), 7,35-7,747 (1H, m), 7,56 (1H, d, J=7,6 Hz), 7,58-of 7.70 (1H, m), 7,87 (1H, t, J=7,6 Hz), 8,12-of 8.25 (1H, m), 8,31 (1H, users), scored 8.38 (1H, d, J=8.0 Hz), 8,58-8,68 (1H, m), 10,80-11,08 (1H, m)

ESI-MS (m/e): 406[M+H]

Example 6:

5-(3-Cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-benzonitrile.

1H NMR (CDCl3) δ: 7,02-was 7.08 (2H, m, 7,14 (1H, d, J=7.5 Hz), 7,20 (1H, DD, J=4.4 Hz, 7.5 Hz), 7,28 and 7.36 (3H, m), 7,39 (1H, t, J=5,9 Hz), 7,42-7,52 (1H, m), 7,88 (1H, dt, J=1.6 Hz, 7.9 Hz), by 8.22 (1H, d, J=3.6 Hz), 8,30 (1H, d, J=3.6 Hz), 8,39 (1H, d, J=7.9 Hz), to 8.62 (1H, d, J=5,9 Hz)

ESI-MS (m/e): 406 [M+H]

Example 7:

5-(4-Cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 4-hydroxy-benzonitrile.

1H NMR (CDCl3) δ: at 6.84 (2H, d, J=7,0 Hz),? 7.04 baby mortality for 7.12 (1H, m), 7,12-7,26 (1H, m), 7,26-the 7.43 (1H, m), 7,30-the 7.43 (1H, m), 7,51 (2H, d, J=7,0 Hz), 7,44-7,76 (1H, m), 7,78-of 7.90 (1H, m), 8,12-8,21 (1H, m), 8,21-8,30 (1H, m,), 8,30-to 8.40 (1H, m), 8,43-8,65 (1H, m), 10,88 (1H, users)

ESI-MS (m/e): 406 [M+H]

Example 8:

5-(4-Dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using dimethylamine 4-hydroxy-benzoic acid.

1H NMR (CDCl3) δ: 3,00 (3H, users), is 3.08 (3H, users), 6,83 (1H, d, J=8,8 Hz)6,86 (1H, d, J=8,8 Hz), 7.18 in-of 7.23 (2H, m), 7,26 and 7.36 (3H, m), 7,38-7,42 (1H, m), to 7.61 (1H, d, J=2.5 Hz), 7,89 (1H, DD, J=7,7, 7,7 Hz), 8,19 is 8.38 (2H, m), at 8.36 (1H, d, J=7,7 Hz), 8,63 (1H, d, J=4,8 Hz)

ESI-MS (m/e): 452 [M+H]

Example 9:

5-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the group receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 4-methanesulfonyl-phenol.

1H NMR (CDCl3) δ: 3,40 (3H, s), of 6.96 (2H, d, J=8,8 Hz), 7,10-7,16 (1H, m), 7,17-of 7.25 (1H, m), 7,32 (1/2H, s), 7,38 (1/2H, s), 7,39-the 7.43 (1H, m), 7,65 (1/2H, s), 7,70 (1/2H, s), 7,83 (2H, DD, J=8,8, 3-l Hz);of 7.90 (1H, DDD, J=7,8, and 7.8, 1.7 Hz), 8,23 (1H, users), 8,32 (1H, users), 8,39 (1H, d, J=7.8 Hz), 8,65 (1H, d, J=4,7 Hz), 10,84 (1H, users)

ESI-MS (m/e): 459 [M+H]

Example 10:

5-(4-Methoxycarbonyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method, but using methyl 4-hydroxybenzoate.

1H NMR (CDCl3) δ: 3,88 (3H, s), PC 6.82 (2H, d, J=8,8 Hz), 7,12 (1H, DDD, J=8,6, to 2.9, 1.5 Hz), 7,18 (1H, DD, J=8,6, 4,8 Hz), 7,28 (1H, users), 7,32 (1H, users), 7,87 (1H, DDD, J=7,7, and 7.7, 1.8 Hz), 7,92 (2H, d, J=8,8 Hz), to 8.20 (1H, d, J=2,9 Hz), of 8.27 (1H, d, J=4,8 Hz), of 8.37 (1H, DD, J=7,7, U Hz), 8,61 (1H, DD, J=5,1, 1.8 Hz), 10,80 (1H, users)

ESI-MS (m/e): 439 [M+H]

Example 11:

5-(2-Formyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 2-hydroxy-benzaldehyde.

1H NMR (CDCl3) δ: 6,80 1H, d, J=8,4 Hz), 6,92-7,58 (6H, m), 7,83 (1H, d, J=8.0 Hz), 7,87 (1H, TD, J=7,6 Hz, 1.2 Hz), 8,12-to 8.34 (3H, m), 8,39 (1H, d, J=8,4 Hz), 8,55-8,67 (1H, m), 10,06 (1H, s)

ESI-MS (m/e): 409 [M+H]

Example 12:

5-(2-Carboxy-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 2-hydroxybenzoic acid.

1H NMR (CD3OD) δ: 6,83 (2H, d, J=8,8 Hz), 7,31 (1H, DDD, J=8,6, 2,9, 1-5 Hz), 7,34 (1H, DDD, J=8,6, 4,8, 0.7 Hz), of 7.48 (1H, DD, J=7,7, 4,8 Hz), 7,54 (1H, s), 7,56 (1H, s), 7,92 (2H, d, J=8,8 Hz), of 7.96 (1H, DDD, J=7,7, and 7.7, 1.5 Hz), of 8.09 (1H, DD, J=2,9, 0.7 Hz), to 8.20 (1H, DD, J=4,8, 1.5 Hz), of 8.27 (1H, d, J=7,7 Hz), 8,72 (1H, d, J=4,8 Hz)

ESI-MS (m/e): 425[M+H]

Example 13:

5-(2-Methyl-pyridine-5-ylsulphonyl)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 2 or in accordance with the method or by combining with an ordinary method but using 6-methyl-pyridine-3-thiol.

1H NMR (CDCl3) δ: of 2.53 (3H, s), 7,05 (1H, d, J=7,6 Hz), 7,05, was 7.36 (tautomer, 1H, C), 7,12-7,24 (2H, m), to 7.32 and 7.36 (1H, m), 7,44, 7,76 (tautomer, 1H, C), 7,50-7,56 (1H, m), 7,83 (1H, t, J=8.0 Hz), compared to 8.26-at 8.36 (3H, m), to 8.45 (1H, ), 8,56 (1H, d, J=4.4 Hz), 11,28-11,40, 11,40-11,50 (tautomer, 1H, users)

ESI-MS (m/e): 412[M+H]

Example 14:

5-(2-Etoxycarbonyl-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in sagola the COC connection receive in the same way, as in example 1 or in accordance with the method or by combining with an ordinary method but using 4-methanesulfonyl-phenol and ethyl 2-hydroxybenzoate.

1H NMR (CDCl3) δ: 1,19 (3H, t, J=7.0 Hz), 3,03 (3H, s), 4,14 (2H, square, J=7,0 Hz), 6.87 in (1H, DD, J=7,4, 6.3 Hz), 7,00 (2H, DD, J=9,0, 2.2 Hz), 7,10-7,17 (1H, m), 7,14 (1/2H, users), 7,32 (1/2H, users), 7,37-the 7.43 (2H, m), 7,49 (1/2H, users), to 7.67 (1/2H, users), 7,81 (2H, DD, J=9,0, 2.2 Hz), 7,82-of 7.90 (2H, m), at 8.36-to 8.40 (1H, m), 8,62-8,64 (1H, m), 10,85 (1H, users)

ESI-MS (m/e): 530[M+H]

Example 15:

5-(2-Dimethylcarbamoyl-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 14, or in accordance with the method or by combining with an ordinary method but using 4-fluoro-5-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and dimethylamide 2-hydroxybenzoic acid.

1H NMR (CDCl3) δ: 2,58-3,06 (9H, m), 6,83 (1/3H, d, J=8.6 Hz), 6,86 (2/3H, d, J=8,4 Hz), 7,02-7,11 (3H, m), 7,12-to 7.18 (2H, m), 7,12-7,18 (1/2H, m), 7.23 percent-7,33 (1H, m), 7.23 percent-7,33 (1/2H, m), of 7.36-7,40 (1H, m), 7,58 (l/3H, s), to 7.64 (2/3H, s), 7,83-of 7.90 (3H, m), 8.34 per is 8.38 (1H, m), 8,62-8,64 (1H, m), of 10.58 (2/3H, users), 10,61 (1/3H, users)

ESI-MS (m/e): 529[M+H]

Example 16:

5-(2-Methoxy-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 2-methoxy-phenol.

1H NMR (CDCl3) δ: 3,03 (3H, s), of 3.69 (3H, s), 6.87 in-to 6.95 (3H, m), 7,00 (1/2H, s), was 7.08 (2H, DD, J=8,9, 2,8 Hz), 7,08-7,38 (1H, m), 7,31 (1/2H, s), 7,35 (1/2H, s), 7,35-7,38 (1H, m), of 7.64 (1/2H, s), 7,83 (2H,, DD, J=8,9, 2,8 Hz), 7,87 (1H, DD, J=7,8, and 1.6 Hz), 8,33 is 8.38 (1H, m), 8,60-to 8.62 (1H, m), to 10.62 (1/2H, users), of 10.73 (1/2H, users)

ESI-MS (m/e): 488[M+H]

Example 17:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 2-hydroxy-benzonitrile.

1H NMR (CDCl3) δ: is 6.78 (1H, d, J=8,4 Hz)6,86 (2H, t, J=9.6 Hz), to 7.09 (1H, DD, J=8,4 Hz to 12.8 Hz), 7,37-of 7.55 (4H, m), 7,62-a 7.92 (4H, m), 8,40 (1H, d, J=8,4 Hz)8,64 (1H, d, J=4.0 Hz)

ESI-MS (m/e): 483[M+H]

Example 18:

5-(4-Dimethylcarbamoyl-phenoxy)-6-phenoxy-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 1 or in accordance with the method or by combining with an ordinary method but using dimethylamine 4-hydroxybenzoic acid and phenol.

1H NMR (CDCl3) δ: 2,99 (3H, users), of 3.07 (3H, users), 6,85-to 6.88 (4H, m), 6,97-7,14 (1H, m), 7,21-7,27 (3H, m), 7,31-7,37 (3H, m), 7,55 (1/2H, users), to 7.61 (1/2H, users), to 7.84 (1H, DDD, J=7,7, and 7.7, 1.5 Hz), 8,35 (1H, d, J=7,7 Hz), 8,61 (1H, users), 10,48 (1/2H, users), 10,51 (1/2H, users)

ESI-MS (m/e): 451[M+H]

Prima is 19:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(4-methylsulfanyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 1 or in accordance with the method or by combining with an ordinary method but using 4-fluoro-5-(4-dimethylcarbamoyl-phenoxy)-2-nitro-phenylamine obtained in example 18, 4-methylmercapto-phenol.

1H NMR (CDCl3) δ: of 2.44 (3H, s)to 2.99 (3H, users), of 3.07 (3H, users), for 6.81 (2H, d, J=8,4 Hz), 6.87 in (2H, d, J=8,4 Hz), 7,18 (2H, d, J=8,4 Hz), 7,10-7,28 (1H, m), 7,32-to 7.35 (1H, m), 7,33 (2H, d, J=8,4 Hz), 7,54 (1/2H, users), 7,60 (1/2H, users), to 7.84 (1H, DD, J=7,7, 7,7 Hz), a 8.34 (1H, d, J=7,7 HZ), 8,59-8,61 (1H, m), 10,55 (1/2H, users), or 10.60 (1/2H, users)

ESI-MS (m/e): 497[M+H]

Example 20:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(2-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 19, or in accordance with the method or by combining with an ordinary method but using 2-methanesulfonyl-phenol.

1H NMR (CDCl3) δ: 2,94 (3/2H, s)to 2.99 (3H, users), 3,03 (3/2H, users), is 3.08 (3H, users), 6,88-6,93 (3H, m), 7,15-7,22 (1H, m), 7,24 (1/2H, s), 7,34-7,42 (3H, m), 7,39 (1/2H, s), 7,45-7,52 (1H, m), of 7.64 (1/2H, s), 7,70 (1/2H, s), 7,86-of 7.90 (1H, m), of 8.00 (1H, d, J=7.8 Hz), scored 8.38 (1H, d, J=7.8 Hz), 8,65 (1H, d, J=3,9 Hz), of 10.72 (1H, users)

ESI-MS (m/e): 529[M+H]

Example 21:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title is information connection receive in the same way, as in example 19, or in accordance with the method or by combining with an ordinary method but using 4-methanesulfonyl-phenol.

1H NMR (CDCl3) δ: 3,00 (3H, users), 3,03 (3H, s), is 3.08 (3H, users), for 6.81 (2H, d, J=8.1 Hz), to 6.95 (2H, d, J=8,4 Hz), 7,26 (1/2H, users), 7,32 (2H, d, J=8.1 Hz), 7,39 (1H, DD, J=7,7, a 4.9 Hz), to 7.64 (1/2H, users), 7,66 (1/2H, users), 7,79 (2H, d, J=8,4 Hz), 7,87 (1H, DDD, J=7,7, and 7.7, 1.8 Hz), of 8.37 (1H, d, J=7,7 Hz), 8,63 (1H, d, J=4.9 Hz), 10,77 (1H, users)

ESI-MS (m/e): 529[M+H]

Example 22:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(4-methoxy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 19, or in accordance with the method or by combining with an ordinary method but using 4-methoxy-phenol.

1H NMR (CDCl3) δ: 3,00-of 3.07 (6H, m), 3,76 (3/2H, s), of 3.77 (3/2H, s), 6,74-6,86 (4H, m)6,91 (2H, d, J=8,4 Hz), 7,05 (1/2H, users), 7,19 (1/2H, users), to 7.32 and 7.36 (1H, m), 7,35 (2H, d, J=8,4 Hz), 7,43 (1/2H, users), 7,58 (1/2H, users), 7,83 (1H, DD, J=7,7, 7,7 Hz), with 8.33 (1H, DD, J=7,7, and 3.7 Hz), 8,58-8,61 (1H, m), of 10.58 (1/2H, users), 10,79 (1/2H, users)

ESI-MS (m/e): 481[M+H]

Example 23:

5-(4-Dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-2-yloxy)-1H-benzimidazole-DATEFORMAT

Specified in the header of the connection get in a solid yellow color in the same way as in example 19, or in accordance with the method or by combining with an ordinary method but using 2-hydroxypyridine.

1H I Is R (CD 3OD) δ: 6,93-7,13 (4H, m), 7,37 was 7.45 (2H, m), 7,41 (1H×1/2, s), 7,56 (NH/2, C)of 7.64 (1H×1/2, (C), to 7.67 to 7.75 (1H, m), to 7.77-to 7.84 (1H, m), 7,81 (1H×1/2, s), 8,02-of 8.06 (1H, m), 8,12-8,20 (1H, m), 8,27-of 8.33 (1H, m), 8,82-8,87 (1H, m)

ESI-MS (m/e): 452[M+H]

Example 24:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(2-etoxycarbonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 19, or in accordance with the method or by combining with an ordinary method, but using ethyl 2-hydroxybenzoate.

1H NMR (CDCl3) δ: of 1.20 (3H, t, J=7.0 Hz), 3,01 (3H, users), of 3.07 (3H, users), 4,17 (2H, square, J=7,0 Hz), 6,80-6,91 (3H, m), 7,08-7,14 (1H, m), 7,12 (1/2H, users), 7,18 (1/2H, users), 7,26-7,41 (4H, m), 7,49 (1/2H, users), to 7.61 (1/2H, users), 7,84-7,87 (2H, m), 8.34 per is 8.38 (1H, m), 8,61-to 8.62 (1H, m), 10,85 (1/2H, users), 10,95 (1/2H, users)

ESI-MS (m/e): 523[M+H]

Example 25:

5-(2-Dimethylcarbamoyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 19, or in accordance with the method or by combining with an ordinary method but using dimethylamine 2-hydroxybenzoic acid.

1H NMR (CDCl3) δ: 2,64-is 3.08 (12H, m), for 6.81 (1/2H, s), 6,85 (1/2H, s)6,94 (1H, DD, J=8,8, 2.7 Hz), 7,08 (1/2H, s), 7,12 (1/2H, s), 7,21 (1/2H, s), 7,24 (1/2H, s), 7,25-7,29 (2H, m), 7,30-7,34 (1H, m), 7,35-7,53 (2H, m), to 7.59 (1H, d, J=3.1 Hz), 7,83-7,88 (1H, m), 8,33 is 8.38 (1H, m), 8,63 (1H, d, J=4.9 Hz), 1052 (1H, users)

ESI-MS (m/e): 522[M+H]

Example 26:

5-(2-Acetyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 19, or in accordance with the method or by combining with an ordinary method but using 2-acetyl-phenol.

1H NMR (CDCl3) δ: 2,36 (3/2H, s), 2.40 a (3/2H, s)of 3.00 (3H, users), is 3.08 (3H, users), 6,76-6,84 (3H, m), 7,05-7,11 (1H, m), 7,15-of 7.25 (1H, m), 7,26-7,28 (1H, m), 7,32-to 7.35 (2H, m), 7,38-7,42 (1H, m), 7,63 (1/2H, s), 7,68 (1/2H, s), 7,78 (1H, d, J=7,4 Hz), 7,86-of 7.90 (1H, m), 8,39 (1H, d, J=7,0 Hz), 8,65 (1H, s), of 10.73 (1H×1/2, users), 10,88 (1H×1/2, users)

ESI-MS (m/e): 493 [M+H]

Example 27:

5-(4-Acetyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 19, or in accordance with the method or by combining with an ordinary method but using 4-acetyl-phenol.

1H NMR (CDCl3) δ: to 2.55 (3H, s), 2,98 (3H, users), to 3.09 (3H, users), 6,70-of 6.90 (4H, m), 7.23 percent (1/2H, s), 7,34 (1/2H, s), 7,26 (1/2H, s), 7,33-to 7.35 (2H, m), 7,38-7,42 (1H, m), 7,65 (1/2H, s), 7,68 (1/2H, s), 7,86-to $ 7.91 (3H, m), 8,40 (1H, d, J=7.8 Hz), 8,65 (1H, d, J=3.5 Hz), 10,85 (1/2H, users), 10,95 (1/2H, users)

ESI-MS (m/e): 493[M+H]

Example 28:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(4-cyano-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 1 or in accordance with the tvii the way, or Association with an ordinary method but using 2-hydroxy-benzonitrile and 4-hydroxy-benzonitrile.

1H NMR (CDCl3) δ: to 6.80 (1H, t, J=8,8 Hz)6,86 (1H, d, J=8,8 Hz), 6.89 in (1H, d, J=8,8 Hz), was 7.08 (1H, dt, J=7,6 Hz, 74 Hz), 7,34-7,47 (3H, m), 7,47-7,58 (3H, m), to 7.67 (1H, d, J=5,2 Hz), 7,88 (1H, t, J=7,6 Hz), scored 8.38 (1H, d, J=7,6 Hz), 8,65 (1H, d, J=4.0 Hz), of 10.58 (1H, users)

ESI-MS (m/e): 430[M+H]

Example 29:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(3-cyano-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 28, or in accordance with the method or by combining with an ordinary method but using 4-fluoro-5-(2-cyano-phenoxy)-2-nitro-phenylamine obtained in example 28, and 3-hydroxy-benzonitrile.

1H NMR (CDCl3) δ: 6,93-6,84 (1H, m), of 6.96 for 7.12 (3H, m), 7,27-7,38 (3H, m), 7,38-of 7.48 (2H, m), 7,54 (1H, DD, J=1.6 Hz and 7.6 Hz), to 7.68 (1H, d, J=13,2 Hz), 7,89 (1H, t, J=7,6 Hz), 8,42 (1H, d, J=7,6 Hz), 8,65 (1H, s)

ESI-MS (m/e): 430[M+H]

Example 30:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(4-(2-hydroxyethyl)phenoxy)-1H-benzimidazole-Monteforte

Specified in the header of the connection get in a solid brown color in the same manner as in example 29, or in accordance with the method or by combining with an ordinary method but using 4-hydroxyethyl-phenol.

1H NMR (CD3OD) δ: 2,78 (2H, t, J=7,0 Hz), and 3.72 (2H, t, J=7.0 Hz), 6,83 (2H, d, J=8.6 Hz), 694 (1H, d, J=8.6 Hz), 7,19-7,21 (3H, m), 7,41 (1H, s), 7,56 (1H, t, J=8.6 Hz), 7,63-7,73 (3H, m), 8,11 (1H, t, J=7.8 Hz), compared to 8.26 (1H, d, J=7.8 Hz), cent to 8.85 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 449[M+H]

Example 31:

5-(4-Cyano-phenoxy)-2-pyridin-2-yl-6-(1-oxy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 1 or in accordance with the method or by combining with an ordinary method but using 1-oxy-pyridine-3-yl and 4-cyano-phenol.

1H NMR (CDCl3) δ: 6,86-of 6.90 (2H, m), 7,11 (1/2H, DDD, J=7,3, 2,8, 1.5 Hz), 7,13 (1/2H, DDD, J=7,3, 2,8, 1.5 Hz), 7,18 (1/2H, DD, J=7,3, 4,8 Hz), 7,20 (1/2H, DD, J=7,3, 4,8 Hz), of 7.36-7,41 (1H, m), 7,37 (1/2H, s), 7,44 (1/2H, s), of 7.48-EUR 7.57 (3H, m), 7,60 (1/2H, s), 7,66 (1/2H, s), 8,20 (1/2H, d, J=2,8 Hz), 8,21 (1/2H, d, J=2,8 Hz), 8.30 to (1/2H, DD, J=4,8, 1.5 Hz), 8,32 (1/2H, DD, J=4,8, 1.5 Hz), of 8.37 (1H, d, J=7,0 Hz), 8,65-to 8.70 (1H, m)

ESI-MS (m/e): 422[M+H]

Example 32:

Getting 2-pyrazin-2-yl-5,6-bis(pyridine-3-yloxy)-1H-benzimidazole

7,7 mg pyrazin-2-carboxylic acid and 20 mg of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (1 ml) 15 mg of 4,5-bis(pyridine-3-yloxy)benzene-1,2-diamine obtained in example 1 (stage 3), and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution, water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent in Privat under reduced pressure and the resulting residue is suspended in 1 ml of phosphorus oxychloride and the reaction liquid was stirred overnight at 100° C. phosphorus Oxychloride is evaporated under reduced pressure and the rest is diluted with ethyl acetate, washed with a saturated solution of sodium bicarbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1+0.1% aqueous ammonia), getting mentioned in the title compound in the form of a solid yellow color.

1H NMR (CD3OD) δ: 7,20-of 7.82 (6H, m), 8,11 (2H, s), 8,20-of 8.28 (2H, m), 8,67 (1H, s), is 8.75 (1H, s), for 9.47 (1H, s)

ESI-MS (m/e): 383[M+H]

Example 33:

5-(4-Methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 32, or in accordance with the method or by combining with an ordinary method but using 4-(4-methanesulfonyl-phenoxy)-5-(pyridine-3-yloxy)benzene-1,2-diamine obtained in example 9.

1H NMR (CDCl3) δ: only 2.91 (3H, s), 3.04 from (3H, d, J=1.6 Hz), of 6.96 (2H, d, J=9.0 Hz), 7,14-to 7.18 (1H, m), 7,19-of 7.25 (1H, m), 7,35 (1/2H, s), 7,41 (1/2H, s), 7,68 (1/2H, s), 7,73 (1/2H, s), to 7.84 (2H, DD, J=9,0, l,6 Hz), 8,24 (1H, DD, J=7,1, 2.7 Hz), 8,32-8,35 (1H, m), 8,59-to 8.62 (1H, m), 8,69 (1H, d, J=2.5 Hz), 9,63-for 9.64 (1H, m), 10,91 (1H×1/2, users), and 10.8 (1H×1/2, users)

ESI-MS (m/e): 460[M+H]

Example 34:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(2-methanesulfonyl-f is noxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 32, or in accordance with the method or by combining with an ordinary method but using 4-(4-dimethylcarbamoyl-phenoxy)-5-(2-methanesulfonyl-phenoxy)benzene-1,2-diamine obtained in example 20.

1H NMR (CDCl3) δ: 2,95 (3/2H, s)to 2.99 (3H, users), 3,05 (3/2H, users), is 3.08 (3H, users), 6,80-6,91 (3H, m), 6.89 in-6,95 (3H, s), 7,17-7,24 (1H, m), 7,20 (1/2H, s), 7,35-7,39 (2H, m), 7,35-7,39 (1/2H, m), 7,46-rate of 7.54 (1H, m), 7,66 (1/2H, s), 7,70 (1/2H, s), 8,02 (1H, d, J=7.8 Hz), at 8.60 (1H, d, J=2.4 Hz), 8,67 (1H, DD, J=2,4, 2.0 Hz), being 9.61 (1H, d, J=2.0 Hz), 10,65 (1/2H, users), a 10.74 (1/2H, users)

ESI-MS (m/e): 530[M+H]

Example 35:

5-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 32, or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-phenoxy)-5-(4-methanesulfonyl-phenoxy)benzene-1,2-diamine obtained in example 17.

1H NMR (CD3OD) δ: to 3.09 (3H, s)6,91 (1H, d, J=7.8 Hz), of 6.96-7,00 (2H, m), to 7.15 (1H, TD, J=7,6 Hz, 1.0 Hz), 7,54-7,58 (1H, m), of 7.64 (1H, DD, J=1.6 Hz, 7.8 Hz), 7,72 (2H, d, J=3.5 Hz), 7,87 (2H, d,J=8.6 Hz), 8,77 (1H, d, J=2.7 Hz), 8,81 cent to 8.85 (1H, DD, J=1.6 Hz, 2.7 Hz), charged 8.52 (1H, d, J=1,6 Hz)

ESI-MS (m/e): 484[M+H]

Example 36:

5-(2-Methoxy-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the floor connection is given the same way as in example 32, or in accordance with the method or by combining with an ordinary method but using 4-(2-methoxy-phenoxy)-5-(4-methanesulfonyl-phenoxy)benzene-1,2-diamine obtained in example 16.

1H NMR (CDCl3) δ: totaling 3.04 (3H, s), 3,71 (3H, d, J=3.1 Hz), 6,86-6,97 (3H, m), 7,00 (1/2H, s), 7,06-7,14 (3H, m), 7,34 (1/2H, s), of 7.36 (1/2H, s), 7,68 (1/2H, s), a 7.85 (2H, DD, J=9,0, 3.1 Hz), 8,56-8,59 (1H, m,), 8,65 (1H, DD, J=4,3, 2.7 Hz), to 9.57-being 9.61 (1H, m), 10,24 (NH/2, users), 10,34 (NH/2, users)

ESI-MS (m/e): 489[M+H]

Example 37

5-(4-Dimethylcarbamoyl-phenoxy)-6-(2-methanesulfonyl-phenoxy)-2-thiazol-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 1 (stage 4), or in accordance with the method or by combining with an ordinary method but using 4-(4-dimethylcarbamoyl-phenoxy)-5-(2-methanesulfonyl-phenoxy)benzene-1,2-diamine obtained in example 20, and thiazole-2-carboxaldehyde.

1H NMR (CDCl3) δ: 2,94 (3/2H, s), 2,96 (3H, users), 3,05 (3/2H, users), is 3.08 (3H, users), 6,87-6,93 (3H, m), 7,13 (1/2H, users), 7,16-of 7.23 (1H, m), 7,34-7,38 (2H, m), 7,45-7,53 (1H, m), 7,51 (1/2H, users), 7,54-7,56 (1H, m), 7,62 (1/2H, s), 7,66 (1/2H, s), 7,94 (1H, d, J=3.1 Hz), 8,01 (1H, DD, J=7,8, 1,6 Hz)

ESI-MS (m/e): 535[M+H]

Example 38:

5-(2-Cyano-phenoxy)-2-pyridazin-3-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

3,3 mg pyridazin-3-carboxylic acid, 15 mg of 1-hydroxybenzotriazole and 15 mg monohydride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution of the N-organic (0.3 ml) 15 mg 4-(2-cyano-phenoxy)-5-(4-methanesulfonyl-phenoxy)benzene-1,2-diamine, obtained in example 17, and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate and washed with saturated sodium hydrogen carbonate solution and the solvent is evaporated under reduced pressure. The resulting residue is dissolved in 0.2 ml of N-methylpyrrolidone and add to it 5 mg triftoratsetata ytterbium and the reaction liquid was stirred overnight at 140°C. the Reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid brown color.

1H NMR (CD3OD) δ: 3,10 (3H, s), 6,92 (1H, d, J=7,6 Hz), of 6.99 (2H, d, J=8.6 Hz), 7,20 (1H, t, J=7,6 Hz), 7,58 (1H, t, J=7,6 Hz), to 7.64 (1H, d, J=7,6 Hz), 7,70-7,80 (2H, m), 7,87 (2H, d, J=8.6 Hz), of 7.96-8,02 (1H, m), 8,58 (1H, users), 9,36 (1H, users)

ESI-MS (m/e): 484[M+H]

Example 39:

5-(2-Cyano-phenoxy)-2-[1,2,5]-thiadiazole-3-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 38, or in accordance with the method or by combining with an ordinary method, but using [1,2,5]-thiadiazole-3-carboxylic acid.

1H NMR (CD3OD) δ: to 3.09 (3H, s), make 6.90 (1H, d, J=7.8 Hz), 6,98 (2H, d, J=8.6 Hz), 7,19 (1H, t, J=7,7 Hz), 7,56 (1H, t, J=7.8 Hz), to 7.64 (1H, d, J=7.8 Hz), 7,72 (1H, s), 7,73 (1H, s), 7,87 (2H, d, J=8.6 Hz), 9,39 (1H, s)

ESI-MS (m/e): 490[M+H]

Example 40:

5-(2-Cyano-phenoxy)-2-(2H-[1,2,3]-triazole-4-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 38, or in accordance with the method or by combining with an ordinary method but using 2H-[1,2,3]-triazole-4-carboxylic acid.

1H NMR (CD3OD) δ: of 3.12 (3H, s)6,91 (1H, d, J=7,6 Hz), 6,98 (2H, d, J=8.6 Hz), 7,20 (1H, t, J=7,6 Hz), 7,56 (1H, t, J=7,6 Hz), to 7.64 (1H, d, J=7,6 Hz), of 7.70 (1H, d, J=2.7 Hz), 7,87 (2H, d, J=8.6 Hz), charged 8.52 (1H, users)

ESI-MS (m/e): 473[M+H]

Example 41:

5-(2-Cyano-phenoxy)-2-furazan-3-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 38, or in accordance with the method or by combining with an ordinary method, but using furazan-3-carboxylic acid.

1H NMR (CD3OD) δ: a 3.06 (3H, s), at 6.84 (1H, d, J=7.8 Hz), 6,92 (2H, d, J=8.6 Hz), to 7.15 (1H, t, J=7.8 Hz), 7,52 (1H, U=7-8 Hz), EUR 7.57 to 7.62 (2H, m), 7,82 (2H, d, J=8.6 Hz)

ESI-MS (m/e): 474[M+H]

Example 42:

5-(2-Cyano-phenoxy)-2-(4H-[1,2,4]-triazole-3-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the compounds is their get in a solid light yellow color in the same way, as in example 38, or in accordance with the method or by combining with an ordinary method, but using [1,2,4]-triazole-3-carboxylic acid.

1H NMR (CD3OD) δ: of 3.07 (3H, s), 6,92 (1H, d, J-7.8 Hz), 6,98 (2H, d, J=8.6 Hz), 7,19 (1H, t, J=7.8 Hz), 7,55 (1H, t, J=7.8 Hz), 7,63 (1H, d, J=7.8 Hz), 7,74 (2H, d, J=6.3 Hz), the 7.85 (2H, d, J=8.6 Hz), 8,73 (1H, s)

ESI-MS (m/e): 473[M+H]

Example 43:

5-(2-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Solution in 80% sulfuric acid 3.5 mg of 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in example 5 was stirred over night at 50°C. the Reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound as a colourless solid.

1H NMR (CDCl3) δ: 5,59 (1H, users), to 6.80 (1H, DD, J=8,4 Hz, 0.8 Hz), 7,01-of 7.48 (7H, m), 7,88 (1H, TD, J=8.0 Hz, 2.0 Hz), 8,16 (1H, DD, J=8,4 Hz, 2.0 Hz), 8,21 (1H, s), 8,27 cent to 8.85 (1H, m), scored 8.38 (1H, d, J=8.0 Hz), 8,63 (1H, d, J=8,4 Hz)

ESI-MS (m/e): 424[M+H]

Example 44:

5-(4-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 43 or in accordance what about the way or Association with an ordinary method but using 5-(4-cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in example 7.

1H NMR (CDCl3) δ: PC 6.82 (2H, d, J=8,8 Hz), 7,13 (1H, DDD, J=8,4, and 2.6, 1.5 Hz), 7,17 (1H, DD, J=8,4, 4,8 Hz), 7,13-7,20 (1H, m), 7,30-7,37 (1H, m), 7,38 (1H, DDD, J=7,7, 4,4, 1.1 Hz), 7,71 (2H, d, J=8,8 Hz), 7,87 (1H, DDD, J=7,7, and 7.7, 1.8 Hz), 8,16 (1H, DD, J=2,6, 0.7 Hz), of 8.25 (1H, DD, J=4,8, 1.5 Hz), 8,39 (1H, DDD, J=7,7, 1,1, 0.7 Hz), 8,61 (1H, DDD, J=4,4, of 1.8, 0.7 Hz)

ESI-MS (m/e): 424[M+H]

Example 45:

5-(4-Carbarnoyl-phenoxy)-6-(pyridine-3-yloxy)-2-thiazol-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 37 and example 43 or in accordance with the method or by combining with an ordinary method but using 4-(4,5-diamino-2-(pyridine-3-yloxy)phenoxy)benzonitrile obtained in example 7.

1H NMR (CDCl3) δ: 6,01 (2H, users), 6,82-6,86 (2H, m), 7,13 (1H, DDD, J=8,4, to 2.9, 1.5 Hz), 7,18 (1H, DD, J=8,4, 4.6 Hz), 7,29 (1/2H, s), 7,30 (1/2H, s), 7,52-rate of 7.54 (1H, m), 7,92 (2H, d, J=8,8 Hz), to 7.61 (1/2H, s), to 7.64 (1/2H, s), 7,70 to 7.75 (2H, m), 7,92 (1H, d, J=2,9 Hz), 8,21 (1H, d, J=2,9 Hz), 8,29 (1H, DD, J=4,6, 1.5 Hz)

ESI-MS (m/e): 430[M+H]

Example 46:

5-(4-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-C the ANO-phenoxy)-2-pyridin-2-yl-6-(4-cyano-phenoxy)-1H-benzimidazole, obtained in example 28.

1H NMR (CD3OD) δ: 7,86 (2H, d, J=8,8 Hz), 7,13 (1H, t, J=7,6 Hz), 7,39 (1H, t, J=7,6 Hz), 7,45-7,74 (4H, m), 7,78 (2H, d, J=8,8 Hz), to $ 7.91 (1H, d, J=7,6 Hz), to 7.99 (1H, t, J=7,6 Hz), 8,30 (1H, d, J=7,6 Hz), a total of 8.74 (1H, s)

ESI-MS (m/e): 466[M+H]

Example 47:

5-(3-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole monotropaceae

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(3-cyano-phenoxy)-1H-benzimidazole obtained in example 29.

1H NMR (CD3OD) δ: 6,78-of 6.96 (1H, m), of 6.96-was 7.08 (1H, m), 7,08-7,20 (1H, m), 7,30-of 7.70 (7H, m), 7,88-8,08 (2H, m), 8,29 (1H, d, J=7,6 Hz), 8,73 (1H, s)

ESI-MS (m/e): 466[M+H]

Example 48:

5-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole obtained in example 17.

1H NMR (CD3OD) δ: of 3.12 (3H, s), 6,85 (1H, d, J=7.8 Hz), 6,98 (2H, d, J=8.6 Hz), to 7.15 (1H, t, J=7.8 Hz), 7,42 (1H, t, J=7.8 Hz), 7,52 (1H, DD, J=4.3 Hz, 7.0 Hz), to 7.64 (2H, users), 7,83 (2H, d, J=8.6 Hz), to $ 7.91 (1H, the, J=7.8 Hz), 8,01 (1H, DD, J=7,0 Hz, 7.8 Hz), 8,32 (1H, d, J=7.8 Hz), 8,76 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 501[M+H]

Example 49:

5-(4-Methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyrazin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole obtained in example 35.

1H NMR (CD3OD) δ: 3,05 (3H, s)5,80 (1H, users), PC 6.82 (1H, d, J=7.8 Hz), 6,95-to 7.00 (3H, m), 7,17 (2H, square, J=8,2 Hz), of 7.36-7,39 (2H, m), 7,76 (1H, d, J=7.8 Hz), 7,81-a 7.85 (2H, m), 8,15 (1H, d, J=7.8 Hz), 8,63 (1H, C)8,72 (1H, s), to 9.66 (1H, s)10,80 (1H, users)

ESI-MS (m/e): 502[M+H]

Example 50:

5-(4-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(1-oxy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(4-cyano-phenoxy)-2-pyridin-2-yl-6-(1-oxy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 31.

1H NMR (CDCl3) δ: 6,82-6,86 (2H, m), 7,15-7,26 (2H, m), 7,38-7,42 (1H, m), 7,41 (1/2H, s), 7,44 (1/2H, s), 7,54-7,58 (1H, m), 7.62mm (1/2H, s), 7,65 (1/2H, s), 7,71 to 7.75 (2H, m), 8,12-8,16 (1H, m), by 8.22-8,27 (1H, m), of 8.37 (1H, d, J=7,0 Hz), 8,64-8,67 (1H, m)

ESI-MS (m/e): 440[M+H]

Example 51:

5-(3-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-ilok and)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(3-cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in example 6.

1H NMR (CDCl3) δ: 7,07 (1H, DDD, J=0,8, 3-4, 10,3 Hz), was 7.36 (1H, DD, J=1,9, 3,4 Hz), 7,40 (1H, t, J=10.3 Hz), 7,56 (1H, s), EUR 7.57 to 7.62 (2H, m), of 7.69 (1H, DD, J=7,2, 10,3 Hz), 7,73 (1H, s), 7,78 (1H, DDD, J=0,8, 3,8, and 11.4 Hz)that is 8.16 (1H, dt, J=3.0 a, and 11.0 Hz), 8,29 (1H, dt, J=0,4, and 11.0 Hz), of 8.37-to 8.41 (2H, m), 8,80 (1H, dt, J=0,4, and 3.8 Hz)

ESI-MS (m/e): 424[M+H]+

Example 52:

5-(2-Carbarnoyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 1 and example 43 or in accordance with the method or by combining with an ordinary method but using 4-fluoro-5-(2-cyano-phenoxy)-2-nitro-phenylamine obtained in example 28, and dimethylamine 4-hydroxybenzoic acid.

1H NMR (CDCl3) δ: 2,98 (3H, users), of 3.07 (3H, users), 5,72 (1H, users), 6,76-6,83 (3H, m), 6,97 (1/2H, users), 7,09 (1/2H, DD, J=7,7, 7,7 Hz), 7,11 (1/2H, DD, J=7,7, 7,7 Hz), 7,14 (1/2H, s), 7,30-to 7.35 (3H, m), 7,37-7,40 (1H, m), to 7.67 (1H, d, J=7,7 Hz), 7,86 (1H, DDD, J=7,7, 7,7, 1-5 Hz)to 8.12 (1H, DD, J=7,7, 1-8 Hz), 8,14 (1H, DD, J=7,7, 1.8 Hz), scored 8.38 (1H, d, J=7,7 Hz), 8,61-to 8.62 (1H, m), 10,99 (1H, users)

ESI-MS (m/e): 494[M+H]

Example 53:

5-(2-Carbarnoyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 37 and example 43 or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-phenoxy)-5-bis-(4-dimethylcarbamoyl-phenoxy)benzene-1,2-diamine obtained in example 52.

1H NMR (CDCl3) δ: of 2.97 (3H, users), is 3.08 (3H, users), 5,91 (1/2H, users), 6,00 (1/2H, users), 6,75-PC 6.82 (3H, m), 6,93 (1/2H, users), 7,07-7,13 (1H, m), 7,17 (1H, users), 7,25 (1/2H, users), 7,32 (2H, d, J=8,8 Hz), 7,53 (1H, d, J=2,9 Hz), the 7.65 (2H, d, J=8,8 Hz), 7,37-7,40 (1H, m), the 7.65 (1H, d, J=7,0 Hz), 7,92-to 7.93 (1H, m), 8,11 (1/2H, d, J=6.6 Hz), 8,13 (1/2H, d, J=6,6 Hz)

ESI-MS (m/e): 500[M+H]

Example 54:

5-(2-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(4-(2-(2,2,2-Cryptor-acetoxy)ethyl)phenoxy)-1H-benzimidazole monotropaceae

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(4-(2-hydroxyethyl)phenoxy)-1H-benzimidazole obtained in example 30, the reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1 to% triperoxonane acid]. The solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound as a colourless solid.

1H NMR (CD3OD) δ: 2,94 (H, t, J=6,7 Hz), 4,17 (2H, t, J=6,7 Hz), at 6.84 (2H, d, J=8.6 Hz), 6.90 to (1H, d, J=8.6 Hz), 7,19 (1H, d, J=8.6 Hz), 7,25 (1H, d, J=8.6 Hz), 7,41 (1H, s), 7,42-of 7.48 (1H, m), 7,58 (1H, s), to 7.61-7,66 (1H, m), of 8.09 (1H, t, J=7.8 Hz), of 8.25 (1H, d, J=7.8 Hz), 8,83 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 563[M+H]

Example 55:

5-(4-Carbarnoyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 1 and example 43 or in accordance with the method or by combining with an ordinary method but using 4-fluoro-5-(4-dimethylcarbamoyl-phenoxy)-2-nitro-phenylamine obtained in example 18, and 4-hydroxy-benzonitrile.

1H NMR (CD3OD) δ: of 2.97 (3H, users), is 3.08 (3H, users), 6,80-6,86 (4H, m), 7,26-7,29 (2H, m), 7,31 (1/2H, s), 7,35 (1/2H, s), 7,38-7,41 (1H, m), 7,66-of 7.70 (3H, m), 7,86-to $ 7.91 (1H, m), 8,40 (1H, d, J=7.8 Hz), 8,65 (1H, d, J=4,7 Hz), 10,89 (1H, users)

ESI-MS (m/e): 494[M+H]

Example 56:

5-(4-Methylcarbamoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

0.05 ml of a solution of 40% methylamine/methanol are added to a solution in methanol (1 ml) 3.0 mg of 5-(4-methoxycarbonyl-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in example 10, and the reaction liquid was stirred overnight at room temperature. The solvent is evaporated under reduced pressure and the rest cleanse distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1)to give specified in the header is VCE connection.

1H NMR (CDCl3) δ: 2,96 (3/2H, s), 2,97 (3/2H, s), to 6.80 (1H, d, J=8,4 Hz), 7,14-of 7.23 (2H, m), of 7.36 (1H, users), 7,40 (1H, DD, J=7,7, a 4.7 Hz), a 7.62 (1H, users), 7,66 (2H, d, J=8,4 Hz), of 7.90 (1H, DD, J=7,7, 7,7 Hz), 8,10 (1H, users), to 8.20 (1H, users), of 8.37 (1H, d, J=7,7 Hz), 8,63 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 438[M+H]

Example 57:

5-(4-Methanesulfonyl-phenoxy)-6-(2-methylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 56, or in accordance with the method or by combining with an ordinary method but using 5-(2-etoxycarbonyl-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 14.

1H NMR (CDCl3) δ: 2,73 (3/2H, s), 2,74 (3/2H, s), 3,03 (3H, s), 6,74-6,79 (1H, m), 6.89 in-76,96 (2H, m), 7,01 (1/2H, users), 7,09-to 7.15 (1H, m), 7,17 (1/2H, users), 7,30 (1/2H, users), 7,40 (1/2H, users), 7,40-7,44 (1H, m), 7,72 (1H, s), 7,82 (2H, DD, J=8,2, 6,7 Hz), 7,88-to 7.93 (1H, m), 8,10-of 8.15 (1H, m), to 8.41 (1H, d, J=6.8 Hz), 8,66 (1H, s), 11,09 (1/2H, users), 11,12 (1/2H, users)

ESI-MS (m/e): 515[M+H]

Example 58:

5-(4-Dimethylcarbamoyl-phenoxy)-6-(2-methylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 56, or in accordance with the method or by combining with an ordinary method but using 5-(2-etoxycarbonyl-phenoxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 24.

1H NMR (CDCl3)δ : 2,77 (3H, d, J=3.5 Hz), 2,99 (3H, users), is 3.08 (3H, users), 6,75-6,86 (3H, m), 7,00-7,14 (1H, m), 7,15-7,27 (1/2H, m), 7,27-to 7.32 (2H, m), 7,27-7,32 (1/2H, m), 7,35-7,42 (2H, m), 7,69 (1H, s), 7,87-to $ 7.91 (1H, m), 8,11-8,17 (1H, m), 8,40 (1H, d, J=7,4 Hz), 8,66 (1H, s), br11.01 (1H, users)

ESI-MS (m/e): 508[M+H]

Example 59:

5-(2-Methylcarbamoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 1 and example 56, or in accordance with the method or by combining with an ordinary method but using 3-(2-fluoro-4-nitro-phenoxy)pyridine obtained in example 1 (stage 2), and methyl 2-hydroxybenzoate.

1H NMR (CDCl3) δ: 2,70-8,80 (3H, m), 6,77 (1H, d, J=7,6 Hz), 7,25-7,44 (7H, m), to 7.67 (1H, s), 7,82 (1H, t, J=7,6 Hz), 8,15 (1H, t, J=7,6 Hz), 8,18 compared to 8.26 (1H, m), compared to 8.26-at 8.36 (1H, m), scored 8.38 (1H, d, J=7,6 Hz)8,64 (1H, d, J=2.4 Hz), or 10.6 (1H, users)

ESI-MS (m/e): 438[M+H]

Example 60:

5-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-(2H-tetrazol-5-yl)phenoxy)-1H-benzimidazole monotropaceae

30 mg of sodium azide and 32 mg of magnesium chloride are added to a solution in dimethylformamide (1 ml) 30 mg of 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-cyano-phenoxy)-1H-benzimidazole obtained in example 17, and the reaction liquid was stirred at 170°C within 24 hours. The reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-AC is control-0,1% triperoxonane acid] and the solvent of the resulting fraction is evaporated under reduced pressure, getting listed in the title compound in the form of a solid yellow color.

1H NMR (CD3OD) δ: 3,11 (3H, s), of 6.75 (2H, d, J=8.6 Hz), of 6.96 (1H, d, J=7,6 Hz), 7,29 (1H, t, J=7,6 Hz), 7,51 (1H, t, J=7,6 Hz), a 7.62 (2H, d, J=8.6 Hz), 7,58-of 7.69 (1H, m), 7,73 (1H, s), to 7.93 (1H, s), 8,13 (1H, d, J=7,6 Hz), 8,08-8,16 (1H, m), 8,33 is 8.38 (1H, m), 8,84-8,88 (1H, m)

ESI-MS (m/e): 526[M+H]

Example 61:

5-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-(2-N-hydroxycarbamoyl)phenoxy)-1H-benzimidazole

0.1 ml of 50% aqueous hydroxylamine are added to a solution in ethanol (2 ml) 25 mg 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-cyano-phenoxy)-1H-benzimidazole obtained in example 17, and the reaction liquid was stirred overnight at 50°C. the Solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=5/1), getting mentioned in the title compound as a colourless solid.

1H NMR (CDCl3) δ: a 3.06 (3H, s), 5,12 (2H, s), of 6.52 (1H, s), to 6.80 (1H, d, J=7,6 Hz), 7,11 (2H, d, J=8.6 Hz), 7,28 (1H, t, J=7,6 Hz), 7,47 (1H, DD, J=7,8 Hz, 4.3 Hz), 7,66 (1H, d, J=7,6 Hz), 7,66 (1H, s), 7,89 (2H,, d, J=8.6 Hz), of 7.96 (1H, t, J=7.8 Hz), 8,55 (1H, d, J=7.8 Hz), 8,65 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 516[M+H]

Example 62:

5-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-(2-oxo-4,5-dihydro-[1,2,4]-oxadiazol-3-yl)phenoxy)-1H-benzimidazole

10 mg of 1,1'-carbonyldiimidazole add to rest the ru in N-methylpyrrolidinone (0.25 ml), 8 mg of 5-(2-(N-hydroxycarbamoyl)phenoxy)-2-pyridin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole, obtained in example 61, and the reaction liquid was stirred at 70°C for 4 hours. The reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], and the obtained fraction was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution and saturated salt solution and then dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as a colourless solid.

1H NMR (CDCl3) δ: of 3.12 (3H, s), at 6.84 (2H, d, J=8.6 Hz), 6,82-to 6.88 (1H, m), 7,19 (1H, t, J=7.2 Hz), 7,41-7,47 (2H, m), 7,82 (2H, d, J=8.6 Hz), to $ 7.91-of 7.97 (2H, m), 8,44 (1H, d, J=7.8 Hz), 8,69 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 542[M+H]

Example 63:

5-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-[1,2,4]-oxadiazol-3-yl-phenoxy)-1H-benzimidazole

0.5 ml of ethyl-orthoformate added to a solution of N-methylpyrrolidinone (0.25 ml), 8 mg of 5-(2-(N-hydroxycarbamoyl)phenoxy)-2-pyridin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole obtained in example 61, and the reaction liquid was stirred at 100°C for 3 hours. The reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], and the solvent of the obtained fractions vepari the try under reduced pressure and it is clear distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid yellow color.

1H NMR (CDCl3) δ: 3,03 (3H, s), 6,85-6,97 (3H, m), 7.23 percent (1H, t, J=7.8 Hz), 7,40 was 7.45 (3H, m), 7.68 per-7,74 (3H, m), to $ 7.91 (1H, t, J=7.8 Hz), 8,03 (1H, d, J=7.8 Hz), 8,42 (1H, d, J=7.8 Hz), 8,65-8,68 (2H, m)

ESI-MS (m/e): 526[M+H]

Example 64:

5-(Pyridine-3-yloxy)-2-pyridin-2-yl-6-(2-(5-methyl-[1,2,4]oxadiazol-3-yl)phenoxy)-1H-benzimidazole

0.3 ml of acetic anhydride are added to a solution in pyridine (0.5 ml) 20 mg 5-(2-(N-hydroxycarbamoyl)phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in the same way as in example 61, but using 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in example 5, and the reaction liquid was stirred overnight at 60°C. the Solvent is evaporated under reduced pressure and it is clear distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CDCl3) δ: 6,80-7,00 (1H, m), 7,00-7,30 (4H, m), 7,30-7,44 (2H, m), 7,44-to 7.68 (1H, m), 7,86 (1H, TD, J=7,6 Hz, 2.0 Hz), of 7.97 (1H, DD, J=2.0 Hz and 7.6 Hz), scored 8.38 (1H, d, J=7,6 Hz), at 8.60 (1H, d, J=4,8 Hz)

ESI-MS (m/e): 463[M+H]

Example 65:

5-(4-Methyl-pyridine-3-sulfonyl)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

92 mg of OXONE and 0.1 ml of water is added to p is the target in tetrahydrofuran (1.5 ml) 42 mg of 5-(2-methyl-pyridine-5-ylsulphonyl)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole, obtained in example 13, and the reaction liquid was stirred overnight at room temperature. The solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. Saturated aqueous sodium hydrogen carbonate solution is added to the obtained fractions and it is extracted with chloroform and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, obtaining specified in the header of the connection.

1H NMR (CDCl3) δ: 2,63 (3H, s), 7.23 percent (1H, s), 7,32 (1H, d, J=7,6 Hz), 7,44 is 7.50 (3H, m), to 7.93 (1H, t, J=7,6 Hz), 8,09-to 8.14 (1H, m), of 8.28 (1H, d, J=2,8 Hz), at 8.36-to 8.41 (2H, m), 8,60, 8,61 (tautomer, 1H, C), 8,68 (1H, d, J=4,8 Hz), 8,93, 8,95 (tautomer, 1H, d, J=2.0 Hz)

ESI-MS (m/e): 444[M+H]

Example 66:

5-(4-Methanesulfonyl-phenoxy)-2-(1-oxo-pyridine-2-yl)-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole

15 mg of metallocarboranes acid are added to a solution in chloroform (2 ml) 8.0 mg of 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole obtained in example 48, and the reaction liquid was stirred at room temperature for 1 hour. The reaction solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase when the average pressure is AI [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid yellow color.

1H NMR (CD3OD) δ: of 3.12 (3H, s), 6.87 in (1H, d, J=7.8 Hz), 7,00 (2H, d, J=7.8 Hz), 7,18 (1H, t, J=7.8 Hz), the 7.43 (1H, t, J=7.8 Hz), 7,69-7,76 (2H, m), 7,84-7,86 (3H, m), 7,92 (1H, d, J=7.8 Hz), charged 8.52 (1H, d, J=7,0 Hz)8,64 (1H, d, J=7,8 Hz)

ESI-MS (m/e): 517[M+H]

Example 67:

4-(2-Methoxy-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 5-fluoro-3-(2-methoxyphenoxy)-2-nitroaniline:

528 mg of sodium hydride are added to a solution in tetrahydrofuran (30 ml) 1.64 g of 2-methoxyphenol under ice cooling and the reaction liquid is stirred for 30 minutes at the same temperature. Then add 1,91 g of 3,5-debtor-2-nitroaniline, which was obtained according to the method described in Journal of Organic Chemistry, 1978, Vol.43, No. 6, pp.1241-1243, and the reaction liquid is stirred for 2 days at room temperature. The reaction liquid was poured into water, extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=5/1 to 4/1), receiving specified in the title compound in the form of solids ora is Zhevago color.

(Stage 2) Obtaining 3-(2-methoxyphenoxy)-2-nitro-5-(pyridine-3-yloxy)aniline:

1.24 g of 3-hydroxypyridine and 5.42 g of potassium carbonate are added to a solution in dimethylformamide (30 ml) 3.03 g of 5-fluoro-3-(2-methoxyphenoxy)-2-nitroaniline and the reaction liquid was stirred overnight at 90°C. the Reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution and then dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=2/1 to 1/1 to 1/2), getting mentioned in the title compound in the form of a solid orange color.

(Stage 3) Obtaining 3-(2-methoxyphenoxy)-5-(pyridine-3-yloxy)benzene-1,2-diamine:

1 g of the catalyst of 20% palladium hydroxide on coal are added to a solution in methanol (20 ml) of 1.33 g of 3-(2-methoxyphenoxy)-2-nitro-5-(pyridine-3-yloxy)aniline and the reaction liquid is stirred for 4 hours in hydrogen atmosphere. The catalyst was removed by filtration, the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/2 to ethyl acetate), obtaining mentioned in the title compound as an oily substance light orange color.

(Stage 4)to Obtain 4-(2-methoxy-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole:

0,026 ml of pyridine-2-carboxaldehyde added to the solution in nitrobenzene (0.5 ml) of 59 mg of 3-(2-methoxyphenoxy)-5-(pyridine-3-yloxy)benzene-1,2-diamine at 120°C and the reaction liquid is stirred for 1 hour at the same temperature. The reaction mixture was purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate to a mixture of chloroform/methanol=20/1). The solvent of the resulting fraction is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CDCl3) δ: 3,79 and 3,83 (total 3H, each s), 6,20-7,40 (9H, m), 7,80-7,88 (1H, m), 8,24-8,65 (4H, m), is 10.68-10,94 (1H, m)

ESI-MS (m/e): 411[M+H]

Example 68:

4-(4-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

18.6 mg pyrazin-2-carboxylic acid and 57.5 mg of the hydrochloride of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide are added to a solution in pyridine (2 ml) to 46.7 mg of 3-(4-pertenece)-5-(pyridine-3-yloxy)benzene-1,2-diamine obtained in the same manner as in example 67, but using 4-terfenol and 3-hydroxypyridine, and the reaction liquid is stirred overnight and then the pyridine is evaporated under reduced pressure. The residue is diluted utilized is that washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, obtaining a mixture of amides in the form of an oily yellow substance. The mixture of amides dissolved in 3 ml of toluene and add it to 28 mg of the monohydrate of p-toluensulfonate acid and the reaction liquid was stirred overnight at 120°C. the Reaction liquid was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1), getting mentioned in the title compound in the form of a solid yellow color.

1H NMR (CDCl3) δ: 6.35mm and 6,53 (total 1H, each d, J=2.0 Hz), 6,77-7,31 (7H, m), 8,32-to 8.40 (2H, m), 8,54 and 8,56 (total 1H, each d, J=1,8 Hz), 8,61 and 8,64 (total 1H, each d, J=2.6 Hz), 9,59 and RS 9.69 (total 1H, each d, J=1.5 Hz), or 10.60 (1H, users)

ESI-MS (m/e): 400[M+H]

Example 69:

6-(4-Methoxy-phenoxy)-4-(1-methyl-1H-imidazol-2-ylsulphonyl)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light brown color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 1-methyl-1H-imidazol-2-t the La and 4-methoxyphenol.

1H NMR (CDCl3) δ: of 3.73 and 3.74 (total 3H, each s), 3,81 (3H, s), of 6.31-7,39 (9H, m), 7,78-7,88 (1H, m), 8.30 and to 8.41 (total 1H, each d, J=7.8 Hz), 8,59 and 8,73 (total 1H, each d, J=4.5 Hz)

ESI-MS (m/e): 430[M+H]

Example 70:

6-(4-Methoxy-phenoxy)-2-pyridin-2-yl-4-(pyridine-2-ylsulphonyl)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using pyridine-2-thiol and 4-methoxyphenol.

1H NMR (CDCl3) δ: 3,80 and 3,81 (total 3H, each s), 6,86 is 7.50 (10H, m), 7,75-7,88 (1H, m), 8,32-to 8.62 (3H, m)

ESI-MS (m/e): 427[M+H]

Example 71:

6-(3-Methoxy-phenoxy)-4-(2-methoxy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-(2-methoxyphenoxy)-2-nitro-5-(pyridine-3-yloxy)aniline obtained in example 67 (stage 2), and 3-methoxyphenol.

1H NMR (CDCl3) δ: of 3.75 (3H, s), 3,79 and 3,84 (total 3H, each s), 6,24-of 7.23 (10H, m), 7,29-7,39 (1H, m), 7,79-7,89 (1H, m), of 8.37 and 8,53 (total 1H, each d, J=7.5 Hz), 8,56-8,65 (1H, m), 10,53-10,83 (1H, m)

ESI-MS (m/e): 440[M+H]

Example 72:

4-(2-Methoxy-phenoxy)-6-(pyridine-3-yloxy)-2-thiazol-2-yl-1H-benzimidazole

Specified in the header soy is inania get in a solid yellow color in the same way, as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-(2-methoxyphenoxy)-5-(pyridine-3-yloxy)benzene-1,2-diamine obtained in example 67 (stage 3), and 2-thiazolecarboxamide.

1H NMR (CDCl3) δ: 3,78 and 3,82 (total 3H, each s), 6,20 and 6,44 (total 1H, each s), 6,68-7,28 (7H, m), 7,43-7,53 (1H, m), 7,88-7,98 (1H, m), 8,29-to 8.41 (2H, m), 10,90-11,10 (1H, m)

ESI-MS (m/e): 417[M+H]

Example 73:

4-(2-Fluoro-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-terfenol.

1H NMR (CDCl3) δ: 6,18-of 6.78 (2H, m), 6,98-7,42 (8H, m), 7,72-of 7.90 (1H, m), by 8.22-8,66 (3H, m), and 11.3 (1H, users)

ESI-MS (m/e): 399[M+H]

Example 74:

4-(4-Fluoro-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 4-terfenol.

1H NMR (CDCl3) δgrades: 6.39 (1H, d, J=2.1 Hz), at 6.84 (1H, d, J=2.1 Hz), 7,17-of 7.25 (4H, m), 7,39 (1H, DD, J=8,4, a 4.7 Hz), was 7.45 (1H, DDD, J=8,4, 2,8, 1.5 Hz), to 7.50 (1H, DD, J=7,7, 4-9 Hz), of 7.96 (1H, DDD, J=7,7, and 7.7, 1.8 Hz), by 8.22 (1H, d, J=7,7 Hz), with 8.33 (1H, DD, J=4,7, 1.5 Hz), scored 8.38 (1H, d, J=2,8 Hz), 8,69 (1H, DDD, J=4,9, 1,8, 1,1 Hz)

ESI-MS (m/e): 399[M+H]

Example 75:

4-(3-Fluoro-phenoxy)-2-pyrid the h-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light brown color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-terfenol.

1H NMR (CDCl3) δ: 6,47-6,98 (5H, m), 7,19-7,39 (4H, m), 7,78-7,89 (1H, m), 8,29-8,48 (3H, m), 8,58 (1H, s)

ESI-MS (m/e): 399[M+H]

Example 76:

2-Pyridin-2-yl-4,6-bis(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-hydroxypyridine.

1H NMR (CD3OD) δ: 7,07 (1H, d, J=2.0 Hz), 7,30 (1H, d, J=2.0 Hz), 7,54 (1H, DDD, J=7,6 Hz, 4.8 Hz, 1.2 Hz), the 7.85-of 7.95 (2H, m), 7,98 (1H, TD, J=7,6 Hz, 2.0 Hz), 8,10-to 8.40 (2H, m), by 8.22 (1H, d, J=8,8 Hz), 8,48 at 8.60 (2H, m), 8,66 (1H, d, J=2 Hz), 8,70-8,82 (2H, m)

ESI-MS (m/e): 382[M+H]

Example 77:

4-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-2-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-cyanophora and 2-hydroxypyridine, as appropriate.

1H NMR (CDCl3) δ: 6,60-7,40 (3H, m), 6,92 (1H, d, J=8.0 Hz), of 6.99 (1H, DD, J=6,4 Hz, 5.2 Hz), to 7.15 (1H, t, J=8.0 Hz), 7,46 (1H, DD, J=8.0 Hz, 2.4 Hz), 7,58-of 7.70 (2H, m), 7,70-of 7.90 (1H, m), 8,18 (1H, DD, J=4,8 Hz, 1.2 Hz), scored 8.38 (1H, d, J=8.0 Hz), at 8.60 (1H, d, J=4.0 Hz), 0,40-11,00 (1H, m)

ESI-MS (m/e): 406[M+H]

Example 78:

4-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-cyanophora.

1H NMR (CDCl3) δ: 6,55 (1/2H, s), 6,69 (1/2H, s)6,70-of 7.55 (8H, m), 7,58-7,72 (1H, m), 7,76-7,80 (1H, m), compared to 8.26-8,48 (3H, m), 8,55-8,64 (1H, m), 10,8-11,4 (1H, m)

ESI-MS (m/e): 406[M+H]

Example 79:

4-(2-Methoxycarbonyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole DATEFORMAT

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method, but using methyl 2-hydroxybenzoate.

1H NMR (CD3OD) δ: 3,70 (3H, s)6,38 (1H, s), 7,14 (1H, s), 7,34 (1H, d, J=7,6 Hz), 7,39 (1H, t, J=7,6 Hz), 7,50 to 7.75 (3H, m), 7,75-7,88 (1H, m), to 7.99 (1H, DD, J=7,6 Hz, 1.2 Hz), 8,07 (1H, t, J=7,6 Hz), 8,27-8,58 (3H, m), 8,72-8,88 (1H, m)

ESI-MS (m/e): 439[M+H]

Example 80:

4-(2-Acetyl-phenoxy)-2-(pyridin-2-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method, but using methyl 2-hydroxyacetophenone.

1H NMR (CDCl3) δ: of 2.68 (3H, s), to 6.58 (1H, d, J=2.3 Hz), 7,19 (1H, DD, J=1,2, 8,2 Hz), 7,31 (1H, DD, J=1,2, 7.5 Hz), 7,35 (1H, DD, J=,0, 7.5 Hz), 7,53 to 7.62 (2H, m), of 7.69 (1H, DD, J=4,7, and 7.8 Hz), 7,76-of 7.82 (1H, m), 7,87 (1H, DD, J=1,0, 8,2 Hz), 8,10 (1H, t, J=7.8 Hz), 8,50-charged 8.52 (1H, m), 8,54 (1H, d, J=2.3 Hz), to 8.62 (1H, d, J=7,0 Hz), a total of 8.74 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 423[M+H]

Example 81:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-it.

1H NMR (CDCl3) δ: 3,62 (3H, s), 6,02-7,40 (8H, m), to 7.84 (1H, t, J=7.2 Hz), with 8.33 (1H, d, J=4.4 Hz), 8,33-of 8.50 (2H, m), charged 8.52-to 8.70 (1H, m)

ESI-MS (m/e): 412[M+H]

Example 82:

6-(4-Dimethylcarbamoyl-phenoxy)-4-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-it 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: 3,03 and 3,09 (total 6H, each s), 3,60, and to 3.64 (total 3H, each s), between 6.08-x 6.15 (1H, m), 6.42 per and 6,64 (total 1H, each s), 6,82-7,41 (8H, m), 7,80-7,88 (1H, m), at 8.36 and 8,45 (total 1H, each d, J=8,2 Hz), 8,59 and 8,64 (total 1H, each d, J=4.5 Hz)

ESI-MS (m/e): 482[M+H]

Example 83:

4-(2-Deformat the XI-pyridine-3-yloxy)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-deformedarse-3-hydroxypyridine and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: 3,02 and 3,09 (total 6H, each s), 6,36 and 6,48 (total 1H, each s), 6,84-to 7.67 (9H, m), 7,83 and 7,88 (total 1H, each t, J=7.8 Hz), 7,99 and 8.00 (total 1H, each d, J=5.0 Hz), 8,40 and 8,42 (total 1H, each d, J=8,4 Hz), 8,61 and 8,64 (total 1H, each d, J=4.3 Hz)

ESI-MS (m/e): 518[M+H]

Example 84:

6-(2-Methyl-pyridine-5-ylsulphonyl)-2-(pyridin-2-yl)-4-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same method as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-hydroxypyridine and 6-methylpyridin-3-thiol, as appropriate.

1H NMR (CDCl3) δ: 2,52 (3H, s), 6,66-to 6.80 (1H, users), 7,05 (1H, d, J=8.0 Hz), 7,20-7,28 (3H, m), 7,32 (1H, m), 7,49 (1H, DD, J=2.0 Hz, 8.0 Hz), 7,81 (1H, t, J=7,6 Hz), 8,32-to 8.40 (3H, m), 8,44 (1H, d, J=2.0 Hz), charged 8.52 (1H, d, J=4,8 Hz), 11,70 to 12.0 (1H, users)

ESI-MS (m/e): 412[M+H]

Example 85:

4-(2-Cyano-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method, or joint the application with the usual way, but using 2-cyanophora and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: 3,05 (3H, s)3,18 (3H, s), 6,62 (1H, s), 6,92-was 7.08 (3H, m), 7,00 (2H, d, J=8,8 Hz), 7,10-7,20 (2H, m), of 7.36-to 7.50 (4H, m), 7,40 (2H, d, J=8,8 Hz), 7,63 (1H, d, J=6.3 Hz), 7,89 (1H, t, J=7,8 Hz), 8,44 (1H, d, J=7.8 Hz), 8,61 (1H, d, J=3,9 Hz)

ESI-MS (m/e): 476[M+H]

Example 86:

4-(2-Fluoro-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-terfenol and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: to 3.02 (3H, s), 3,10 (3H, s), to 6.39 (1H, s), 6,92-to 7.00 (3H, m), of 6.96 (2H, d, J=9.0 Hz), 7,10-7,24 (4H, m), of 7.36-7,42 (3H, m), 7,39 (2H, d, J=9.0 Hz), 7,88 (1H, d, J=7,7 Hz), 8,51 (1H, d, J=8.0 Hz,), 8,63 (1H, d, J=7,7 Hz)

ESI-MS (m/e): 469[M+H]

Example 87:

4-(2-Fluoro-phenoxy)-2-(pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-terfenol and 4-(methanesulfonyl)phenol, as appropriate.

1H NMR (CDCl3) δ: is 3.08 (3H, s), 6,44 (1H, s), was 7.08 (2H, d, J=9.0 Hz), 7.18 in-EUR 7.57 (5H, m), to 7.59 (1H, DD, J=3.1 and 8.2 Hz), of 7.90 (2H, d, J=9.0 Hz), of 8.06 (1H, t, J=7,6 Hz)8,64 (1H, d, J=8,2 Hz), 8,71 (1H, d, J=7,6 Hz)

ESI-MS (m/e): 476[M+H]/p>

Example 88:

4-(2-(1-Hydroxy-ethyl)phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-(1-hydroxyethyl)phenol and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: to 1.48 (3H, d, J=6.4 Hz), 3,05 (3H, s), 3,10 (3H, s), of 5.26 (1H, square, J=6.4 Hz), 6,34 (1H, s),? 7.04 baby mortality (2H, d, J=9.0 Hz), 7,05-7,10 (2H, m), 7,29-7,33 (2H, m), 7,44 (2H, d, J=9.0 Hz), EUR 7.57 (1H, DD, J=the 4.7 and 7.6 Hz), to 7.68 (1H, DD, J=2.0 a, 7,4 Hz), of 8.04 (1H, dt, J=1,6, 7,8 Hz), of 8.37 (1H, d, J=7.8 Hz), 8,80 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 495[M+H]

Example 89:

4-(2-Methanesulfonyl-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-(methanesulfonyl)phenol and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: a 3.06 (3H, s), 3,14 (3H, s), 3,49 (3H, s), 7,03 (1H, d, J=2.0 Hz), 7,11 (2H, d, J=8,8 Hz), 7,22 (1H, d, J=8.0 Hz), 7,32-7,40 (2H, m), 7,42 (1H, d, J=2.0 Hz), of 7.48 (2H, d, J=9.0 Hz), EUR 7.57 (1H, DD, J=4,9, and 7.8 Hz), 7,63 (1H, DD, J=1,8, 7.9 Hz), 8,00 (1H, dt, J=1,6, 7,8 Hz), 8,14 (1H, DD, J=1,8, 8.0 Hz), charged 8.52 (1H, d, J=8.0 Hz), the rate of 8.75 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 529[M+H]

Example 90:

4-(2-Acetyl-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-shall benzimidazol

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-hydroxy-acetophenone and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: of 2.68 (3H, s), 3,10 (3H, s), 3,20 (3H, s), to 6.67 (1H, s), 7,05 (2H, d, J=8,2 Hz), 7,15-7,22 (2H, m), 7,35 (1H, t, J=7.0 Hz), was 7.45 (2H, d, J=8,2 Hz), 7,55 (1H, t, J=7.0 Hz), 7,60-to 7.64 (1H, m), 7,86 (1H, d, J=7,4 Hz), 8,08-to 8.14 (1H, m)8,64 (1H, d, J=7,4 Hz), 8,75-8,77 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 91:

4-(2-Dimethylcarbamoyl-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-hydroxy-N,N-dimethylbenzamide and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: 2,99 (3H, s), 3,06 (6H, s), 3,17 (3H, s), 6,91-6,94 (1H, m),? 7.04 baby mortality (2H, d, J=8.6 Hz), 7,06-7,10 (1H, m), 7,17 (1H, t, J=7.4 Hz), 7,28-7,39 (4H, m), 7,42 (2H, d, J=8.6 Hz), to 7.84 (1H, t, J=7,8 Hz), to 8.41 (1H, d, J=7.8 Hz), 8,68 (1H, d, J=3,9 Hz)

ESI-MS (m/e): 522[M+H]

Example 92:

4-(2,5-Debtor-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method, but using 2,5-dif is orfanou and 4-hydroxy-N,N-dimethylbenzamide, accordingly.

1H NMR (CDCl3) δ: to 3.02 (3H, s), 3,14 (3H, s), 6,52-6,55 (1H, m), 6.90 to-6,99 (2H, m), 7,02 (2H, d, J=8,2 Hz), 7,10 (1H, d, J=2.0 Hz), 7,16-7,24 (1H, m), 7,42 (2H, d, J=8,2 Hz), 7,54-of 7.60 (1H, m), of 8.06 (1H, dt, J=1,6, 7,8 Hz), 8,61 (1H, d, J=7.8 Hz), 8,72 (1 H, d, J=4,7 Hz)

ESI-MS (m/e): 487[M+H]

Example 93:

4-(2,4-Debtor-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method, but using 2,4-differenoe and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: of 3.00 (3H, s)to 3.09 (3H, s), of 6.31 (1H, s), of 6.99 (1H, s), 7,02 (2H, d, J=8.6 Hz), 7,10-of 7.25 (2H, m), 7,28-7,40 (1H, m), the 7.43 (2H, d, J=8.6 Hz), 7,49-7,52 (1H, m), 7,98 (1H, d, J=7.8 Hz), a 8.34 (1H, d, J=7.9 Hz), a total of 8.74 (1H, d, J=3,9 Hz)

ESI-MS (m/e): 487[M+H]

Example 94:

4-(2,6-Debtor-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method, but using 2,6-differenoe and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: to 3.02 (3H, s), 3,14 (3H, s), to 6.39 (1H, s)to 7.00 (2H, d, J=8.6 Hz), 7,06-to 7.18 (3H, m), 7,20-of 7.25 (1H, m), 7,41 (2H, d, J=8.6 Hz), of 7.48-7,51 (1H, m), to 7.99 (1H, dt, J=1,6, 7,8 Hz), 8,59 (1H, d, J=8,2 Hz), to 8.70 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 487[M+H]

Example 5:

4-(2-Methoxy-phenoxy)-2-(pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 71, or in accordance with the method or by combining with an ordinary method but using 4-(methanesulfonyl)phenol.

1H NMR (CDCl3) δ: 3,03 (3H, s), with 3.79 (3H, s), 6,32 (1H, s), 6,92-6,99 (1H, m), 7,00 (1H, s), 7,06 (2H, d, J=8.6 Hz), 7,10-7,22 (3H, m), 7,38-the 7.43 (1H, m), 7,83 (2H, d, J=8.6 Hz), of 7.90 (1H, t, J=7,8 Hz)and 8.50 (1H, d, J=7.8 Hz), 8,64 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 488[M+H]

Example 96:

6-(4-Dimethylcarbamoyl-phenoxy)-4-(1-ethyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 1-ethyl-3-hydroxy-1H-pyridine-2-it 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: to 1.38 (3H, t, J=6.8 Hz), 3,02 and 3,09 (total 6H, each s)4,06 (2H, square, J=6,8 Hz), x 6.15 (1H, t, J=7.0 Hz), 6,40-7,42 (9H, m), 7,78-7,86 (1H, m), 8,32-8,42 (1H, m), 8,57-8,66 (1H, m)

ESI-MS (m/e): 496[M+H]

Example 97:

6-(6-Methyl-pyridine-3-ylphenyl)-4-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-2-(pyridin-2-yl)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with ordinary the m way but using 4-methyl-4H-[1,2,4]triazole-3-thiol and 6-methyl-pyridine-3-thiol, as appropriate.

1H NMR (CDCl3) δ: to 2.55 (3H, s), 3,71 (3H, s), 7,17 (1H, d, J=8.0 Hz), 7,20-7,24 (1H, users), 7,42-7,46 (1H, m), to 7.59 (1H, DD, J=2,4 Hz, 8.0 Hz), 7,66-to 7.68 (1H, users), to $ 7.91 (1H, t, J=8.0 Hz), 8,32 is 8.38 (3H, m), to 8.70 (1H, d, J=4,8 Hz)

ESI-MS (m/e): 432[M+H]

Example 98:

4-(4-Fluoro-phenoxy)-2-(5-methyl-isoxazol-3-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using 5-methylisoxazol-3-carboxylic acid.

1H NMR (DMSO-d6) δ: of 2.50 (3H, s)6,40 (1H, s), to 6.80 (1H, s), PC 6.82 (1H, users), 7,14-7,24 (4H, m), 7,38 (1H, DD, J=8,2, a 4.7 Hz), 7,44 (1H, d, J=7,7 Hz), 8,32 (1H, d, J=4,7 Hz), at 8.36 (1H, d, J=2.5 Hz)

ESI-MS (m/e): 403[M+H]

Example 99:

4-(4-Fluoro-phenoxy)-2-(1-methyl-1H-imidazol-4-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using 1-methyl-1H-imidazole-4-carboxylic acid.

1H NMR (DMSO-d6) δ: and 3.72 (3H, s)6,38 (1H, d, J=1,8 Hz), for 6.81 (1H, d, J=1,8 Hz), 7,05-7,13 (2H, m), 7,17 (2H, t, J=8,8 Hz), of 7.36-the 7.43 (2H, m), of 7.75 (1H, s), 7,78 (1H, d, J=1.1 Hz), of 8.28 (1H, s), 8,35 (1H, d, J=2,2 Hz)

ESI-MS (/e): 402 [M+H]

Example 100:

4-(4-Fluoro-phenoxy)-2-(3-methyl-[1,2,4]thiadiazole-5-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole monotropaceae

Specified in the header of the connection get in a solid brown color in the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using 3-methyl[1,2,4]thiadiazole-5-carboxylic acid obtained according to the method of EP 0726260 or Association with a customary method.

1H NMR (DMSO-d6) δ: 2,70 (3H, s), 6,44 (1H, d, J=2.2 Hz), 6.87 in (1H, s), 7,15-7,27 (4H, m), 8,39 (1H, DD, J=4,5, 1.5 Hz), 8,44 (1H, d, J=2.5 Hz)

ESI-MS (m/e): 420[M+H]

Example 101:

4-(4-Fluoro-phenoxy)-2-isoxazol-3-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using isoxazol-3-carboxylic acid.

1H NMR (CD3OD) δ: 6,41 (1H, d, J=2.4 Hz), 7,01 (1H, d, J=2.4 Hz), 7,02-7,20 (5H, m), 7,51 (1H, DD, J=4.4 Hz, and 8.4 Hz), to 7.59 (1H, DD, J=2,4 Hz and 8.4 Hz), 8,32 (1H, d, J=4.4 Hz), 8,35 (1H, d, J=2.4 Hz), 8,84 (1H, d, J=2,4 Hz)

ESI-MS (m/e): 389[M+H]

Example 102:

4-(4-Fluoro-phenoxy)-2-pyrimidine-4-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using pyrimidine-4-to benovoy acid.

1H NMR (CDCl3) δ: 2,60 (3H, s), 6,98-7,40 (8H, m), 8,30-of 8.50 (2H, m), 8,63 (1H, s), the 10.40-11,00 (1H, m)

ESI-MS (m/e): 400[M+H]

Example 103:

4-(4-Fluoro-phenoxy)-2-pyrimidine-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using pyrimidine-2-carboxylic acid.

1H NMR (CD3OD) δ: 6.42 per (1H, s), 6,98 (1H, s), 7,10-7,30 (5H, m), of 7.36-of 7.60 (2H, m), by 8.22-8,42 (2H, m), 8,90-9,10 (1H, m), 9,20 (1H, s)

ESI-MS (m/e): 400 [M+H]

Example 104:

4-(4-Fluoro-phenoxy)-2-(1H-imidazol-2-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using 1H-imidazole-2-carboxylic acid.

1H NMR (CD3OD) δ: 6,44 (1H, d, J=2.0 Hz), 7,00 (1H, d, J=2.0 Hz), 7,05-to 7.18 (4H, m), 7,25 (2H, s), 7,39 (1H, DD, J=3.2 Hz, and 8.4 Hz), 7,42-7,50 (1H, m), compared to 8.26 (1H, DD, J=1.6 Hz, 4.4 Hz), 8,29 (1H, d, J=3.2 Hz)

ESI-MS (m/e): 388[M+H]

Example 105:

4-(4-Fluoro-phenoxy)-2-(1-methyl-1H-imidazol-2-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method, but using l-methyl-1H-imidazole-2-carboxylic acid.

1H NMR (CDCl3) δ: 3,98 of 4.3 (3H, m), 6,38-6,60 (1H, m), 6,60-to 6.80 (1H, m), 6,80-7,40 (8H, m), 8,20-8,44 (2H, m)

ESI-MS (m/e): 402[M+H]

Example 106:

4-(4-Fluoro-phenoxy)-6-(pyridine-3-yloxy)-2-[1,2,4]thiadiazole-5-yl-1H-benzimidazole

Specified in the title compound obtained as an oily material light yellow color in the same manner as in example 68, or in accordance with the method or by combining with an ordinary method, but using [1,2,4]thiadiazole-5-carboxylic acid, obtained in the method of comparative example 1.

1H NMR (CD3OD) δ: 6.42 per (1H, s), 6.90 to-of 7.23 (5H, m), 7,39-to 7.50 (2H, m), 8,25-8,32 (2H, m), 8,86 (1H, s)

ESI-MS (m/e): 406[M+H]

Example 107:

4-(2,6-Debtor-phenoxy)-2-(pyrazin-2-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method, but using 2,6-differenoe and 4-(methanesulfonyl)phenol, as appropriate.

1H NMR (CDCl3) δ: 3,03 (3H, s), 6,28 (1H, s), was 7.08 (1H, s), 7,17 (2H, d, J=9.4 Hz), 7,19-7,24 (2H, m), 7,30-7,40 (1H, m), to 7.93 (2H, d, J=9.4 Hz), 8,70 is 8.75 (1H, m), 8,77-8,82 (1H, m), of 9.55-a 9.60 (1H, m)

ESI-MS (m/e): 495[M+H]

Examples 108-1, 108-2:

4-(2-Oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole and 4-(2-methoxy-pyridine-3-yloxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

Listed in the connection header get in the same way as Primera 68, or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-2-methoxypyridine, 3-hydroxypyridine and Pikalyovo acid, as appropriate.

4-(2-Oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

1H NMR (CDCl3) δ: 6,10-to 7.35 (8H, m), to 7.77-to 7.84 (1H, m), 8,30-to 8.41 (3H, m), 8,53 (1H, d, J=4.4 Hz)

ESI-MS (m/e): 398[M+H]

4-(2-Methoxy-pyridine-3-yloxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole

1H NMR (CDCl3) δ: 3,95 and to 3.99 (total 3H, each s), 6.25 and 6,45 (total 1H, each s), 6,80 was 7.45 (6H, m), 7,79-of 7.90 (1H, m), of 8.00 (1H, d, J=1.5 Hz), 8.30 to-8,63 (4H, m)

ESI-MS (m/e): 412[M+H]

Examples 109-1, 109-2:

6-(4-Dimethylcarbamoyl-phenoxy)-4-(2-methoxy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole and 6-(4-dimethylcarbamoyl-phenoxy)-4-(2-oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Listed in the connection header receives the same way as in examples 108-1 and 108-2, or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-2-methoxypyridine, 4-hydroxy-N,N-dimethylbenzamide and Pikalyovo acid, as appropriate.

6-(4-Dimethylcarbamoyl-phenoxy)-4-(2-methoxy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

1H NMR (CDCl3) δ: 3,03 and is 3.08 (total 6H, each s), 3,95 and 4,00 (total 3H, each s), 6,27 and 6,47 (total 1H, each d, J=1,8 Hz), 6,80 was 7.45 (8H, m), 7,80-to $ 7.91 (1H, is), 7,98-8,03 (1H, m), and scored 8.38 8,48 (total 1H, each d, J=7.8 Hz), 8,61 and 8,64 (total 1H, each d, J=4,8 Hz)

ESI-MS (m/e): 482[M+H]

6-(4-Dimethylcarbamoyl-phenoxy)-4-(2-oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

1H NMR (CDCl3) δ: 3,03 and is 3.08 (total 6H, each s), 6,18 and 6.23 (total 1H, each t, J=7.0 Hz), 6,52 and was 6.73 (total 1H, each d, J=1,8 Hz), 6,80-7,42 (8H, m), 7,79 and 7,84 (total 1H, each t, J=7.8 Hz), of 8.37 and 8,40 (total 1H, each d, J=7.8 Hz), 8,56 and to 8.57 (total 1H, each d, J=5.0 Hz)

ESI-MS (m/e): 468[M+H]

Example 110:

4-(2-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole DATEFORMAT

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(pyridine-3-yloxy)-1H-benzimidazole obtained in example 78.

1H NMR (CD3OD) δ: of 6.61 (1H, d, J=2.0 Hz), 7,19 (1H, d, J=8.0 Hz), 7,22 (1H, s), 7,31 (1H, TD, J=7,6 Hz, 1.2 Hz), of 7.48-of 7.60 (2H, m), 7,72-7,80 (1H, m), 7,83 (1H, DD, J=7,6 Hz, 1.2 Hz), 7,87-of 7.95 (1H, m), 8,03 (1H, TD, J=8.0 Hz, 1.2 Hz), 8,01 (1H, DD, J=7,6 Hz, 1.2 Hz), to 8.45 (1H, d, J=5,2 Hz), 8,48-8,54 (1H, m), 8,76-8,84 (1H, m)

ESI-MS (m/e): 424[M+H]

Example 111:

4-(2-Carbarnoyl-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 110, or in accordance with the method or by combining with the usual way, but with and the use of 4-(2-cyano-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole, obtained in example 85.

1H NMR (CDCl3) δ: 2,99 (3H, s), is 3.08 (3H, s), 6,56 (1H, s), 6,86-6,92 (1H, m), to 6.95 (2H, J=8,9 Hz),? 7.04 baby mortality-was 7.08 (2H, m), 7,30-7,38 (4H, m), of 7.36 (2H, d, J=8,9 Hz), 7,52 (1H, d, J=7,6 Hz), 7,80 (1H, t, J=7.9 Hz), at 8.36 (1H, d, J=7.9 Hz), charged 8.52 (1H, d, J=3,7 Hz)

ESI-MS (m/e): 494[M+H]

Example 112:

4-(2-(N-hydroxycarbamoyl)phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 61, or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole obtained in example 85.

1H NMR (CDCl3) δ: to 3.02 (3H, s), and 3.16 (3H, s), is 6.61 (1H, d, J=2.0 Hz), to 6.95 (1H, d, J=2.0 Hz), 6,97 (2H, d, J=8.6 Hz), 7,14-7,22 (2H, m), 7,38 (2H, d, J=8.6 Hz), 7,52 (1H, DD, J=4,9, a 7.6 Hz), 7,56 to 7.62 (1H, m), 7,63-to 7.67 (1H, m), of 7.97 (1H, dt, J=1,6, 7,8 Hz), 8,48 (1H, d, J=7.8 Hz), 8,68 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 509[M+H]

Example 113:

4-(2-(5-Methyl-[1,2,4]-oxadiazol-3-yl)phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 64, or in accordance with the method or by combining with an ordinary method but using 4-(2-(N-hydroxycarbamoyl)phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole obtained in example 112.

1H NMR (CDCl3) δ: 2,70 (3H, s), to 3.02 (3H, s)and 3.15 (3H, s)6,91 (1H), ? 7.04 baby mortality (2H, d, J=8.6 Hz), 7,30-7,38 (3H, m), 7,44 (2H, d, J=8.6 Hz), 7,50-7,58 (2H, m), 7,95 (1H, d, J=7.8 Hz), 8,02 (1H, t, J=7.8 Hz), 8,63 (1H, d, J=8.6 Hz), 8,71 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 533[M+H]

Example 114:

4-(2-(5-Oxo-4,5-dihydro-[1,2,4]-oxadiazol-3-yl)phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 62, or in accordance with the method or by combining with an ordinary method but using 4-(2-(N-hydroxycarbamoyl)phenoxy)-2-(pyridin-2-yl)-6-(4-dimethylcarbamoyl-phenoxy)-1H-benzimidazole obtained in example 112.

1H NMR (CDCl3) δ: totaling 3.04 (3H, s)and 3.15 (3H, s), 6,74 (1H, s), of 6.99 (2H, d, J=8.6 Hz), 7,10 (1H, s), 7,28 and 7.36 (2H, m), 7,44 (2H, d, J=8.6 Hz), 7,50-7,58 (2H, m), 7,89 (1H, d, J=7.8 Hz), 8,00-8,07 (1H, m), 8,56-8,64 (2H, m)

ESI-MS (m/e): 535[M+H]

Example 115:

4-(4-Fluoro-phenoxy)-2-(pyrazole-1-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 4-(4-fluoro-phenoxy)-6-(pyridine-3-yloxy)-1H-benzimidazole-2-thiol:

0.06 ml of carbon disulfide and 54 mg of potassium hydroxide are added to a solution in ethanol (2.0 ml) 273 mg of 3-(4-fluoro-phenoxy)-5-(pyridine-3-yloxy)benzene-1,2-diamine obtained in example 68, the reaction liquid was stirred overnight at 80°C. the Reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, obtaining the criminal code is mentioned in the header of the connection.

(Stage 2) Getting (4-(4-fluoro-phenoxy)-6-(pyridine-3-yloxy)-1H-benzimidazole-2-yl)hydrazine:

1.0 ml of hydrazine monohydrate is added to 130 mg of 4-(4-fluoro-phenoxy)-6-(pyridine-3-yloxy)-1H-benzimidazole-2-thiol and the reaction liquid was stirred overnight at 130°C. the Reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), hexane/ethyl acetate=1/1)to give specified in the header of the connection.

(Stage 3) to Obtain 4-(4-fluoro-phenoxy)-2-(pyrazole-1-yl)-6-(pyridine-3-yloxy)-1H-benzimidazole:

0,012 ml tetramethoxypropane added to a solution in ethanol (0.3 ml) of 8.3 mg (4-(4-fluoro-phenoxy)-6-(pyridine-3-yloxy)-1H-benzimidazole-2-yl)hydrazine and the reaction liquid was stirred overnight at 80°C. the reaction Solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1)to give specified in the header of the connection.

1H NMR (CDCl3) δ: 6,36 (1H, d, J=2.6 Hz), 6.48 in-6,51 (2H, m), 6,77 (1H, d, J=2.6 Hz), 7,05 (2H, d, J=6.9 Hz), 7,11-to 7.18 (1H, m), 7,22-7,28 (2H, m), 7,72 to 7.75 (1H, m), 8,30 is 8.38 (2H, m), 8,48 (1H, d, J=3.8 Hz)

ESI-M (M/e): 388 [M+H]

Example 116:

4-(4-Fluoro-phenoxy)-6-(pyridine-3-yloxy)-2-[1,2,4]triazole-1-yl-1H-benzimidazole

(Stage 1) preparation of 4-(4-fluoro-phenoxy)-2-methylsulfanyl-6-(pyridine-3-yloxy)-1H-benzimidazole:

30 mg of potassium carbonate and of 0.014 ml under the conditions added to the solution in dimethylformamide (1.0 ml) 78 mg of 4-(4-fluoro-phenoxy)-6-(pyridine-3-yloxy)-1H-benzimidazole-2-thiol obtained in example 115, and the reaction liquid was stirred at 0°C for 30 minutes. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, obtaining specified in the header of the connection.

(Stage 2) Obtaining 4-(4-fluoro-phenoxy)-2-methanesulfonyl-6-(pyridine-3-yloxy)-1H-benzimidazole:

84 mg of metallocarboranes acid are added to a solution in chloroform (1.0 ml) 80 mg of 4-(4-fluoro-phenoxy)-2-methylsulfanyl-6-(pyridine-3-yloxy)-1H-benzimidazole and the reaction liquid was stirred at 0°C for 30 minutes. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), ethyl acetate), obtaining the is shown in the header of the connection.

(Stage 3) to Obtain 4-(4-fluoro-phenoxy)-6-(pyridine-3-yloxy)-2-[1,2,4]triazole-1-yl-1H-benzimidazole:

5.0 mg of sodium hydride are added to a solution in dimethylformamide (0.5 ml) 16 mg of 4-(4-fluoro-phenoxy)-2-methanesulfonyl-6-(pyridine-3-yloxy)-1H-benzimidazole and then to this type of 10.4 mg [1,2,4]-triazole and the reaction liquid was stirred overnight at 160°C. the Reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), ethyl acetate), obtaining specified in the header of the connection.

1H NMR (CDCl3) δ: 6.42 per (1H, s), 7.03 is-to 7.15 (3H, m), 7,19 (1H, s), 7,27-to 7.32 (3H, m)to 8.12 (1H, s), 8,32 is 8.38 (2H, m)to 9.15 (1H, s)

ESI-MS (m/e): 389[M+H]

Example 117:

5-Chloro-2-pyridin-2-yl-4,6-bis(pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 3-chloro-2,4-bis(pyridine-3-yloxy)nitrobenzene:

628 mg 3 hydroxypyridine and 1,82 g of potassium carbonate are added to a solution in dimethylformamide (8 ml) 679 mg [1,2,3]-trichloro-4-nitrobenzene, and the reaction liquid was stirred at 100°C for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried alpacamania. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate), obtaining mentioned in the title compound as an oily material light yellow color.

(Stage 2) Obtain 3-chloro-2,4-bis(pyridine-3-yloxy)aniline:

963 mg of ammonium chloride and 503 mg of iron powder is added to a suspension of 1.2 g of 3-chloro-2,4-bis(pyridine-3-yloxy)-nitrobenzene in 15 ml of methanol and 7.5 ml of water and the reaction liquid is heated at the boil under reflux for 3 hours. The reaction liquid is filtered and the solvent is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate), obtaining mentioned in the title compound as an oily material light yellow color.

(Stage 3) Obtain 3-chloro-2,4-bis(pyridine-3-yloxy)-6-nitroaniline:

315 mg of potassium nitrate are added to a solution in triperoxonane acid (20 ml) 891 mg of 3-chloro-2,4-bis(pyridine-3-yloxy)aniline and the reaction liquid was stirred overnight at room temperature and then the solvent issue the mandate under reduced pressure. The residue is diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate), obtaining mentioned in the title compound in the form of a solid orange color.

(Stage 4) to Obtain 4-chloro-3,5-bis(pyridine-3-yloxy)benzene-1,2-diamine:

128 mg of ammonium chloride and 67 mg of iron powder is added to the suspension 143 mg of 3-chloro-2,4-bis(pyridine-3-yloxy)-6-nitroaniline in 8 ml of methanol and 4 ml of water and the reaction liquid is heated at the boil under reflux for 2 hours. The reaction liquid is filtered and the solvent is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated, getting mentioned in the title compound in the form of a solid light brown color.

(Stage 5) to Obtain 5-chloro-2-pyridin-2-yl-4,6-bis(pyridine-3-yloxy)-1H-benzimidazole:

In the same manner as in example 68, but using 4-chloro-3,5-bis(pyridine-3-yloxy)benzene-1,2-diamine and Pikalyovo acid specified in the title compound obtained as the firmness of the Dogo substances light yellow color.

1H NMR (DMSO-d6) δ: 7,18 to 7.62 (6H, m), 7,92 and to 7.99 (total 1H, each dt, J=8,0, 1.8 Hz), 8,10-8,44 (5H, m), 8,66-8,72 (1H, m)

ESI-MS (m/e): 416, 418 [M+H]

Example 118:

5-Methyl-2-pyridin-2-yl-4,6-bis(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 117, or in accordance with the method or by combining with an ordinary method, but using 2,4-debtor-3-methylnitrobenzene obtained according to the method described in Chemical and Pharmaceutical Bulletin, 1982, Vol.30, No. 10, pp.3530-3543.

1H NMR (DMSO-d6) δ: 2,03 and 2.10 (total 3H, each s), 7,01 is 7.50 (6H, m), 7,88 and 7,87 (total 1H, each dt, J=7,7, 1,6 Hz), 8,06-to 8.41 (5H, m), 8,63-to 8.70 (1H, m)

ESI-MS (m/e): 396[M+H]

Example 119:

5-fluoro-2-pyridin-2-yl-4,6-bis-(pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 117, or in accordance with the method or by combining with an ordinary method, but using [1,2,3]-Cryptor-4-nitrobenzene.

1H NMR (DMSO-d6) δ: 7,21-7,63 (6H, m), of 7.90 shed 8.01 (1H, m), 8,12-8,39 (3H, m), 8,43-of 8.50 (2H, m), 8,63-8,73 (1H, m)

ESI-MS (m/e): 400[M+H]

Example 120:

4-(2-Cyano-phenoxy)-6-(4-N,N-dimethylcarbamoyl-phenylsulfonyl)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of 5-(4-carboxy-phenylsulfanyl)-3-(2-cianfrocca)-2-nitro-phenylamine:

31 mg of 4-what mercaptobenzoic acid and 55 mg of potassium carbonate are added to a solution in dimethylformamide (2 ml) 47 mg of 3-(2-cianfrocca)-5-fluoro-2-nitro-phenylamine, obtained in example 78, and the reaction liquid was stirred at 60°C for 2 hours. The reaction liquid concentrate and 1 ml triperoxonane acids are added to the residue and the solvent is evaporated under reduced pressure. The resulting residue is purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid orange color.

(Stage 2) Obtaining 3-(2-cianfrocca)-5-(4-N,N-dimethylcarbamoyl-phenylsulfanyl)-2-nitro-phenylamine:

0,059 ml dimethylamine (2.0 M solution in tetrahydrofuran), 28 mg of the hydrochloride of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide and 20 mg, hydrate, N-hydroxybenzotriazole are added to a solution in dichloromethane (2 ml) 40 mg 5-(4-carboxy-phenylsulfanyl)-3-(2-cianfrocca)-2-nitro-phenylamine and the reaction liquid was stirred at room temperature for 1.5 hours. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium hydrogen carbonate solution and saturated salt solution and then dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound in the form of a yellow powder is about color.

(Stage 3) Obtaining 3-(2-cianfrocca)-5-(4-N,N-dimethylcarbamoyl-phenylsulfanyl)benzene-1,2-diamine:

19 mg of electrolytic powder and 0.2 ml of aqueous saturated solution of ammonium chloride are added to a solution in isopropyl alcohol (2 ml), 32 mg of 3-(2-cianfrocca)-5-(4-N,N-dimethylcarbamoyl-phenylsulfanyl)-2-nitro-phenylamine and the reaction liquid is heated at the boil under reflux for 2 hours. The catalyst was removed by filtration and the solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

(Stage 4) to Obtain 3-(2-cianfrocca)-5-(4-N,N-dimethylcarbamoyl-phenylsulfonyl)benzene-1,2-diamine:

38 mg of metallocarboranes acid are added to a solution in dichloromethane (2 ml) 25 mg 3-(2-cianfrocca)-5-(4-N,N-dimethylaminoethanol-phenylsulfanyl)benzene-1,2-diamine and the reaction liquid was stirred at room temperature for 15 minutes. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the obtained OST is OK purify distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound as yellow powder.

(Stage 5) to Obtain 4-(2-cyano-phenoxy)-6-(4-N,N-dimethylaminoethyl-phenylsulfonyl)-2-(pyridin-2-yl)-1H-benzimidazole:

Specified in the header of the connection get in a solid brown color in the same manner as in example 67 (stage 4), or in accordance with the method or by combining with an ordinary method but using 3-(2-cianfrocca)-5-(4-N,N-dimethylaminoethanol-phenylsulfonyl)benzene-1,2-diamine.

1H NMR (CDCl3) δ: 2,91 and 2,92 (total 3H, each s), 3,10 (3H, s), of 6.99 (1H, m), 7.23 percent-7,30 (1H, m), 7,39-7,46 (2H, m), 7,50-7,58 (3H, m), 7.68 per for 7.78 (1H, m), 7.75, and 8,33 (total 1H, each s), the 7.85 and a 7.92 (total 1H, each t, J=8,4 Hz), 7.95 is-to 8.20 (2H, m), 8,39 and 8,42 (total 1H, each d, J=8,4 Hz), 8,63-8,67 (1H, m)

ESI-MS (m/e): 524[M+H]

Example 121:

1-(2-(6-(4-Oxazol-5-yl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of ethyl 3-bromo-4-methoxyethoxymethyl:

5.5 g of sodium hydride are added to a solution in tetrahydrofuran (300 ml) of 20.5 g of ethyl 3-bromo-4-hydroxybenzoate obtained according to the method described in Monatsh. Chem.; 22; 1901; 437 while cooling with ice and the reaction liquid is stirred for 30 minutes and then at the same temperature, 10 ml of chloromethyl methyl simple ether added to the reaction liquid and the reaction W is dcost stirred over night at room temperature. The reaction liquid was diluted with ethyl acetate and washed with water and the aqueous layer was extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting solid is suspended in hexane and then collected by filtration, getting mentioned in the title compound in the form of a solid white color.

(Stage 2) Obtain tert-butyl 2-(5-etoxycarbonyl-2-methoxyethoxy-phenyl)pyrrol-1-carboxylate:

21 g of 1-(tert-butoxycarbonyl)pyrrol-2-Bronevoy acid and 4.2 g tetranitroaniline palladium and 153 ml of an aqueous solution of sodium carbonate (2 M) is added appropriately to the solution of dimethoxyethane (350 ml) 21 g of ethyl 3-bromo-4-methoxyethoxymethyl and the reaction liquid is heated overnight at boiling under reflux in a nitrogen atmosphere. After cooling, the reaction liquid was diluted with water, extracted with chloroform and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=12/1 to 10/1), getting mentioned in the title compound in the form of a solid white color.

(Stage 3) to Obtain tert-butyl 2-(5-etoxycarbonyl-2-methoxyethoxy-phenyl)pyrrolidin-1-carboxylate:/p>

of 8.2 g of a catalyst of 5% platinum on coal are added to a solution in ethanol (400 ml) 28.4 g of tert-butyl 2-(5-etoxycarbonyl-2-methoxyethoxy-phenyl)pyrrol-1-carboxylate and the reaction liquid is stirred for 3 hours in hydrogen atmosphere. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/6,5 to 1/6), getting mentioned in the title compound as a colorless oily substance.

(Stage 4) to Obtain ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-hydroxybenzoate:

13 g of the monohydrate of p-toluensulfonate acid are added to a solution of 26 g of tert-butyl 2-(5-etoxycarbonyl-2-methoxyethoxy-phenyl)pyrrolidin-1-carboxylate in a mixture of 250 ml of ethanol and 50 ml of water and the reaction liquid is heated at the boil under reflux for 2 days. After cooling, the reaction liquid was diluted with water, neutralized aqueous sodium bicarbonate, extracted with a mixed solvent of chloroform/methanol (10/1) and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to give crude product. 13 ml of acetic anhydride are added to a solution in pyridine (200 ml) of the obtained crude product and stirred. After 2 hours add 6 ml of uksosn the th anhydride. After another 1 hour, add 150 ml of pyridine and after another 40 minutes there is added 5 ml of triethylamine. After another 30 minutes add 3 ml of acetic anhydride and the reaction liquid is stirred for 30 minutes. The reaction liquid was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate and the aqueous layer was extracted with ethyl acetate. The combined organic layers dried with anhydrous magnesium sulfate and the solvent is evaporated under reduced pressure to give crude product. 10 g of potassium carbonate are added to a solution in methanol (200 ml) of the obtained crude product, and the reaction liquid is stirred for 4 hours at room temperature. The reaction liquid is distilled under reduced pressure and the obtained residue was diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. This extract is dried with anhydrous magnesium sulfate, then the solvent is evaporated under reduced pressure and the resulting solid is collected by filtration with ethyl acetate, getting mentioned in the title compound in the form of a solid white color.

(Stage 5) to Obtain ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-benzyloxybenzoate:

15 g of potassium carbonate and 6.4 ml of benzylbromide added to the solution in dimethylformamide (100 ml) and 12.4 g of ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-hydroxybenzoate and implement the operating fluid is stirred at 50° C for 1 hour. The reaction liquid is cooled, diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer is washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=10/1 to 1/2 to 1/3), getting mentioned in the title compound as an oily yellow substance.

(Stage 6) Obtaining 3-(1-acetyl-pyrrolidin-2-yl)-4-benzyloxybenzyl acid:

23 ml of aqueous 4n solution of sodium hydroxide are added to a solution in ethanol (200 ml) to 18.7 g of ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-benzyloxybenzoate and the reaction liquid was stirred overnight at room temperature. 15 ml of aqueous 4n solution of sodium hydroxide is added to the reaction liquid and the reaction liquid is stirred for 7 hours. The reaction solvent is evaporated under reduced pressure and the resulting residue diluted with water and washed with simple ether. The aqueous layer was acidified by adding 6N hydrochloric acid, then extracted with chloroform and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

(Stage 7) Sex is the significance of tert-butyl (3-(1-acetyl-pyrrolidin-2-yl)-4-benzyloxy-phenyl)carbamate:

3.0 ml of diisopropylethylamine and 3.8 ml diphenylphosphoryl azide are added to a solution of 5 g of 3-(1-acetyl-pyrrolidin-2-yl)-4-benzyloxybenzyl acid in a mixture of 15 ml of toluene and 15 ml of 2-methyl-2-propanol and the reaction liquid is heated overnight at boiling under reflux. After cooling, a saturated salt solution and aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, and it is extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/0 to 1/1 to 0/1)to give specified in the title compound as a colorless amorphous substance.

(Stage 8) to Obtain 1-(2-(4,5-diamino-2-benzyloxy)-phenyl)pyrrolidin-1-yl-ethanone:

1.1 g of potassium nitrate are added to a solution in triperoxonane acid (50 ml) 4.1 g of tert-butyl (3-(1-acetyl-pyrrolidin-2-yl)-4-benzyloxy-phenyl)carbamate and the reaction liquid was stirred overnight at room temperature. The reaction solvent is evaporated under reduced pressure and add ice water to the obtained residue. Then neutralized aqueous ammonia and diluted with ethyl acetate. The precipitate is collected by filtration, to give crude product as a solid brown color is the same. The filtrate is diluted with aqueous saturated sodium chloride solution, extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, the obtained residue is purified column chromatography on silica gel (manifesting solvent: ethyl acetate) and the resulting solid is suspended in ethyl acetate and collected by filtration, to give crude product as a solid brown color. 1.5 ml of hydrazine monohydrate and 1 g of the catalyst of Raney Nickel with a developed surface add accordingly to a solution in ethanol (100 ml) 2.8 g of the obtained crude product, and the reaction liquid was stirred at room temperature for 3 hours. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure. The obtained residue was diluted with saturated aqueous sodium bicarbonate, extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/0 to 99/1 to 98/2 to 97/3 to 96/4 to 93/7), getting mentioned in the title compound as a green amorphous substance.

(Stage 9) to Obtain 1-(2-(6-benzyloxy-2-pyridin-2-yl-3-(2-trimethylsilyl-oxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

3 ml solution in toluene 460 mg of pyridine-2-carboxaldehyde added to a solution in toluene (43 ml) of 1.39 g of 1-(2-(4,5-diamino-2-benzyloxy)-phenyl)pyrrolidin-1-yl-ethanone and the reaction liquid was stirred at room temperature. After 2 hours add 46 mg of pyridine-2-carboxaldehyde and the reaction liquid was stirred at 90°C for 2 hours. Additionally added 46 mg of pyridine-2-carboxaldehyde and the reaction liquid was stirred at 90°C for 10 hours. After cooling, the precipitated solid is collected by filtration, to give crude product as a solid brown color. 144 mg of sodium hydride and 667 mg 2-(chloromethoxy)ethyltrimethoxysilane added to the solution in tetrahydrofuran (20 ml), 1.1 g of the obtained crude product, and the reaction liquid was stirred at room temperature for 2.5 hours. Aqueous saturated sodium bicarbonate is added to the reaction liquid, and extracted it with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: ethyl acetate), obtaining mentioned in the title compound as an amorphous substance brown.

(Stage 10) to Obtain 1-(2-(6-hydroxy-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-be imidazol-5-yl)pyrrolidin-1-yl)ethanone:

713 mg of ammonium formate and 119 mg of the catalyst 20% palladium hydroxide on coal are added to a solution in ethanol (20 ml) 1.18 g of 1-(2-(6-benzyloxy-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone and the reaction liquid is heated at the boil under reflux for 5 hours. 157 mg of ammonium formate and 56 mg of the catalyst 20% palladium hydroxide on coal added to the reaction liquid and the reaction liquid is additionally heated at the boil under reflux for 1 hour. After cooling, the catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure. The obtained residue was diluted with 1N hydrochloric acid, extracted with ethyl acetate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/0 to 99/1 to 98/2), getting mentioned in the title compound as an amorphous substance brown.

(Stage 11) to Obtain 1-(2-(6-(4-oxazol-5-yl-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

30 mg of 5-(4-bromo-phenyl)oxazol, 56 mg of cesium carbonate and 15 mg of copper oxide (II) are added to a solution of pyridine (1 ml) 29 mg of 1-(2-(6-hydroxy-2-pyridin-2-yl-3-(2-trimethyl who Ranil-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone and the reaction liquid was stirred overnight in a sealed tube at 120° C. After cooling, aqueous saturated solution of ammonium chloride and a saturated solution of salt added accordingly in the reaction liquid is extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=12/1)to give specified in the title compound as an oily yellow substance.

(Stage 12) to Obtain 1-(2-(6-(4-oxazol-5-yl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

24 mg of 1-(2-(6-(4-oxazol-5-yl-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone dissolved in 1 ml triperoxonane acid and the reaction liquid was stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase at medium pressure (ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid), getting mentioned in the title compound as an oily yellow substance.

1H NMR (CDCl3) δ: 1,73-2,69 (7H, m), 3,54-3,91 (2H, m), to 5.21-of 5.48 (1H, m,), 6,91-7,98, 8,30-8,51, 8,57-8,73 ( 13H, each m)

ESI-MS (m/e): 466[M+H]

Example 122:

3-(6-(1-Acetyl-pyrrolidin-2-the l)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile:

Specified in the title compound obtained as an oily substance in the same manner as in example 121 (stage 11), (stage 12), or in accordance with the method or by combining with an ordinary method but using 1-(2-(6-hydroxy-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 121 (step 10) and 3-sinobambusa.

1H NMR (CDCl3) δ: 1,80-2,42 (7H, m), 3,56-3,93 (2H, m), 5,14-of 5.45 (1H, m), 6,91-7,73 (7H, m), 7,80-of 7.96 (1H, m), 8.30 to-8,43 (1H, m), 8,58-to 8.70 (1H, m), of 10.58-was 10.82 (1H, m)

ESI-MS (m/e): 424[M+H]

Example 123:

3-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-benzamide:

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 3-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile obtained in example 122.

1H NMR (CDCl3) δ: 1,70-2,39 (7H, m), 3,39-to 3.89 (2H, m), 5,17-6,24 (3H, m), 6,97-a 7.92 (8H, m), compared to 8.26-8,42 (1H, m), charged 8.52-8,67 (1H, m), 10,42-of 10.72 (1H, m)

ESI-MS (m/e): 442[M+H]

Example 124:

5-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile:

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-bromo-pyridine-2-ka is bontril.

1H NMR (CDCl3) δ: 1,50-2,42 (7H, m), 3,56-3,88 (2H, m), 5,09-of 5.40 (1H, m), 6.89 in-7,92 (6H, m), compared to 8.26-to 8.70 (3H, m), 10,63 is 11.05 (1H, m)

ESI-MS (m/e): 425[M+H]

Example 125:

Amide 5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carboxylic acid:

Specified in the title compound obtained as an oily substance in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile obtained in example 124.

1H NMR (CDCl3) δ: 0,60-2,42 (7H, m), 3,42-are 3.90 (2H, m), 4,99-5,80 (2H, m), 6,74-8,67 (10H, m), 10,42-10,10,85 (1H, m)

ESI-MS (m/e): 443[M+H]

Examples 126-1, 126-2:

1-(2-(6-(5-Bromo-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

1-(2-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Listed in the connection header receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-bromo-2-methanesulfonyl-pyridine.

1-(2-(6-(5-Bromo-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

1H NMR (CDCl3) δ: 1,50-to 2.40 (7H, m), 3,50-a 3.87 (2H, m,), 5,03-5,14, 5,31-5,42 ( 1H, each m), 6,71-7,88, 10,48-11,15 (7H, each m), 8,08-to 8.40 (2H, m), 8,50-8,69 (1H, m)

ESI-MS (m/e): 478, 480[M+H]

1-(2-(6-(6-M is canalphones-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

1H NMR (CDCl3) δ: 1,57-2,59 (7H, m), is 3.08-of 3.27 (3H, m), 3,57-to 3.89 (2H, m), 5,14-of 5.40 (1H, m), 6,94-to 7.64 (4H, m), 7,82-of 8.15 (2H, m), 8,33 is 8.75 (3H, m)

ESI-MS (m/e): 478[M+H]

Example 127:

1-(2-(2-Pyridin-2-yl-6-(quinoline-6-yloxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 6-bromo-quinoline.

1H NMR (CDCl3) δ: 1,67-2,69 (7H, m), 3,40-Android 4.04 (2H, m), 5.25 to 5,63 (1H, m), 6,80-9,13 (12H, m), 10,22-11,44 (1H, br)

ESI-MS (m/e): 450[M+H]

Example 128:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-2-methyl-benzonitrile

Specified in the title compound obtained as an oily substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromo-2-methyl-benzonitrile.

1H NMR (CDCl3) δ: 1,48-2,54 (10H, m), 3,20-to 3.89 (2H, m), 5,06-5,41 (1H, m), 6,80-8,87 (10H, m)

ESI-MS (m/e): 438[M+H]

Example 129:

1-(2-(2-Pyridin-2-yl-6-(4-triptoreline-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 1-bromo-4-triptoreline-benzene.

1H NMR (CDCl3) δ: 1,43-2,69 (7H, m), 3,32-3,91 (2H, m), 5,20-5,59 (1H, m), 6,23-8,97 (11N, m)

ESI-MS (m/e): 483[M+H]

Example 130:

1-(2-(2-Pyridin-2-yl-6-(quinoline-3-yloxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 3-bromo-quinoline.

1H NMR (CDCl3) δ: 1,00-2,47 (7H, m), 3,37-4,00 (2H, m), 5,26 is 5.54 (1H, m), 6,98-9,10 (12H, m), 10,44-of 10.73 (1H, m)

ESI-MS (m/e): 450[M+H]

Example 131:

1-(2-(6-(4-Acetyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 1-(4-iodine-phenyl)ethanone.

1H NMR (CDCl3) δ: 1,47-2,60 (10H, m), 3,52-3,88 (2H, m), 5,12-5,41 (1H, m), 6,97-7,74 (6H, m), 7,80-8,02 (3H, m), 8.30 to-8,44 (1H, m), 8,57-to 8.70 (1H, m)

ESI-MS (m/e): 441[M+H]

Example 132:

1-(2-(6-(Biphenyl-4-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromo-biphenyl.

1H NMR (CDCl3) δ: 1,13-2,47 (H, m), 3,40-3,91 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,72-7,89 (13H, m), 8,25-8,42 (1H, m), 8,42-8,67 (1H, m), 10,29-or 10.60 (1H, m)

ESI-MS (m/e): 475[M+H]

Example 133:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-N,N-dimethyl-benzosulfimide

Specified in the title compound obtained as an oily substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-iodine-N,N-dimethyl-benzosulfimide.

1H NMR (CDCl3) δ: 1,50-3,00 (13H, m), 3,40-to 3.92 (2H, m), 5,14-of 5.50 (1H, m), 6,40-8,80 (11N, m)

ESI-MS (m/e): 506[M+H]

Example 134:

1-(2-(6-Biphenyl-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 3-bromo-biphenyl.

1H NMR (CDCl3) δ: 0,80-of 2.50 (7H, m), 3,40-3,91 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-7,95 (13H, m), 8,25-to 8.45 (1H, m), 8,50-to 8.70 (1H, m)

ESI-MS (m/e): 475[M+H]

Example 135:

1-(2-(6-(4-Propan-2-sulfonyl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 1-iodine-4-(propane-2-sulfonyl)benzene.

1H NMR (CDCl3) δ: 1,10-of 2.50 (13H, m), 3,05-3,30 (1H, m), 3,50-3,95 (2, m)of 5.05-of 5.50 (1H, m), 7,00-of 7.95 (8H, m), 8,30-and 8.50 (1H, m), 8,58 is 8.75 (1H, m), or 10.60-10,95 (1H, m)

ESI-MS (m/e): 505[M+H]

Example 136:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-2-trifluoromethyl-benzonitrile

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromo-2-trifluoromethyl-benzonitrile.

1H NMR (CDCl3) δ: 1,10-of 2.45 (7H, m), 3,50-of 3.95 (2H, m), 5,00-of 5.45 (1H, m), 6,60-of 7.95 (7H, m), 8,30-to 8.45 (1H, m), 8,55 is 8.75 (1H, m), 10,80-11,60 (1H, m)

ESI-MS (m/e): 492[M+H]

Examples 137-1, 137-2:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-2-trifluoromethyl-benzamide monotropaceae

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-N-ethyl-2-trifluoromethyl-benzamide monotropaceae

Listed in the connection header receive the same manner as in example 43 and example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-2-trifluoromethyl-benzonitrile obtained in example 136.

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-2-trifluoromethyl-benzamide monotropaceae

1H NMR (CD3OD) δ: 1,05 is 2.80 (7H, m), 3,50-4,20 (2H, m), and 5.30-of 5.45 (1H, m), 7,30-7,80 (6H, m), 8,05-to 8.20 (1H, m), 8,20 is 8.38 (1H, m), 8,80-of 8.90 (1H, m)

ESI-MS (m/e): 510[M+H]

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-N-ethyl-2-trifluoromethyl-benzamide monotropaceae

1H NMR (CD3OD) δ: 1,05 is 2.80 (10H, m), 3,60-of 4.05 (2H, m), 4.80 to 5,00 (2H, m), and 5.30-of 5.45 (1H, m), 7,30-7,80 (5H, m), 8,05-to 8.20 (1H, m), 8,20 is 8.38 (1H, m), 8,80-of 8.90 (1H, m), 9,10-of 9.30 (1H, m)

ESI-MS (m/e): 538[M+H]

Example 138:

1-(2-(6-(4-(2-Dimethylamino-ethoxy)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 2-(4-iodine-phenoxy)ethyl)dimethylamine.

1H NMR (CDCl3) δ: 1,05-2,90 (13H, m), 3.00 and is 4.45 (6H, m), 5,20-of 5.45 (1H, m), 6,80-of 8.00 (8H, m), 8,25-to 8.40 (1H, m), 8,50-8,80 (1H, m)

ESI-MS (m/e): 486[M+H]

Example 139:

1-(2-(6-(4-Hydroxymethyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromo-benzyl alcohol.

1H NMR (CDCl3) δ: 1,68-to 2.40 (7H, m), 3,53-3,88 (2H, m), to 4.62-4.72 in (2H, m), 5,22-to 5.56 (1H, m), 6,82 to 7.62 (7H, m), 7,80-7,89 (1H, m), 8,32-to 8.40 (1H, m), 8,55-8,64 (1H, m)

ESI-MS (m/e): 429 [M+H]

Example 140:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-N,N-dimethyl-benzamide

The decree of the TES in the title compound obtained as a solid substance of white color in the same way, as in example 122 or in accordance with the method or by combining with an ordinary method but using dimethylamine 4 bramantino acid.

1H NMR (CDCl3) δ: 1,81-to 2.40 (7H, m), 2,98-3,17 (6H, m), 3,56-a 3.87 (2H, m), 5,20-of 5.53 (1H, m), 6,93-the 7.65 (7H, m), 7,81-7,89 (1H, m), 8,33-to 8.41 (1H, m), 8,60-8,67 (1H, m)

ESI-MS (m/e): 470[M+H]

Example 141:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-N-methyl-benzamide

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromo-N-methylbenzamide.

1H NMR (CDCl3) δ: 1,80-2,39 (4H, m), 1,84 and 2.16 (total 13H, each s), 2,98-to 3.02 (3H, m), to 3.58-3,74 (1H, m), 3,78-a 3.87 (1H, m), 5,16-5,43 (1H, m), 6,74-7,89 (8H, m), at 8.36-8,39 (1H, m), 8,63-8,66 (1H, m)

ESI-MS (m/e): 456[M+H]

Example 142:

1-(2-(2-Pyridin-2-yl-6-(4-(pyrrolidin-1-carbonyl)phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method, but using (4-bromo-phenyl)pyrrolidin-1-yl-ethanone.

1H NMR (CDCl3) δ: 1,80-to 2.40 (8H, m), 1,87, and of 2.21 (total 13H, each s), 3,43-to 3.52 (2H, m), 3,60-3,71 (3H, m), 3,81-are 3.90 (1H, m), to 5.21-of 5.50 (1H, m), 6,84-7,02 (2H, m), 7,25-7,58 (5H, m), 7,83-to 7.93 (1H, m), at 8.36-to 8.45 (1H, m), 8,62-8,67 (1H, is)

ESI-MS (m/e): 496[M+H]

Example 143:

1-(2-(6-(4-(Morpholine-4-carbonyl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method, but using (4-bromo-phenyl)morpholine-4-yl-methanone.

1H NMR (CDCl3) δ: 1,78-2,62 (7H, m), 3,40-3,90 (10H, m), 5,23-of 5.50 (1H, m), 6,82-rate of 7.54 (7H, m), 7,86-7,94 (1H, m), scored 8.38-8,46 (1H, m), 8,64-8,69 (1H, m)

ESI-MS (m/e): 512[M+H]

Example 144:

Monotropaceae 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzoic acid

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromo-benzoic acid.

1H NMR (CDCl3) δ: 1,86 and 2.10 (total 3H, each s), 1,92-2,48 (4H, m), 3,41-are 3.90 (2H, m), are 5.36 of 5.39 (1H, m), 7,13-7,72 (5H, m), 8,00-8,07 (3H, m), by 8.22 compared to 8.26 (1H, m), 8,73-8,80 (1H, m)

ESI-MS (m/e): 443[M+H]

Example 145:

1-(2-(6-(4-(piperidine-1-carbonyl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with the conventional method, but the application of (4-bromo-phenyl)-piperidine-1-yl-methanone.

1H NMR (CDCl3) δ: 1,45-to 2.40 (10H, m), 1,88, and 2,20 (total 3H, each s), 3,30-are 3.90 (6H, m), 5,23-of 5.53 (1H, m), 6,83-of 7.55 (7H, m), 7,84-7,94 (1H, m), of 8.37-8,46 (1H, m), 8,63-8,68 (1H, m)

ESI-MS (m/e): 510[M+H]

Example 146:

1-(2-(6-(4-(4-Acetyl-piperazine-1-carbonyl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 1-(4-(4-bromo-benzoyl)-piperazine-1-yl)ethanone.

1H NMR (CDCl3) δ: 1,84-to 2.40 (10H, m), 3,24-3,88 (10H, m), 5,22-of 5.48 (1H, m), 6,94-to 7.09 (2H, m), 7,22-of 7.48 (5H, m), 7,84-to 7.93 (1H, m), of 8.37-8,43 (1H, m), 8,63-8,66 (1H, m)

ESI-MS (m/e): 553[M+H]

Example 147:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile

(Stage 1) preparation of 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)benzonitrile:

of 5.8 mg of sodium hydride are added to a solution in N-methyl-pyrrolidinone (1 ml) 30 mg 1-(2-(6-hydroxy-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 121 (step 10), and 20 mg of 4-fortunently and the reaction liquid was stirred overnight in a sealed tube at 100°C. After cooling, aqueous saturated bicarbonate sodium is added to reacciona the liquid, then it is extracted with ethyl acetate, the organic layer washed with water and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound as an oily yellow substance.

(Stage 2) Obtaining 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile:

Specified in the title compound obtained as an oily substance in the same manner as in example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)benzonitrile.

1H NMR (CDCl3) δ: 1,52-2,42 (7H, m), 3,42-to 3.92 (2H, m), 5,02-of 5.40 (1H, m), 6,77 to 7.75 (7H, m), 7,75-7,94 (1H, m), 8,20-8,46 (1H, m), 8,50-8,69 (1H, m), 10,67-11,06 (1H, m)

ESI-MS (m/e): 424[M+H]

Example 148:

4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzamide

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile obtained in example 47.

1H NMR (CDCl3) δ: 1,05-to 2.40 (7H, m), 3.43 points-to 3.89 (2H, m), 5,10-6,32 (3H, m), 6,88-of 7.90 (8H, m), 8,27-8,42 (1H, m), 8,53-8,68 (1H, m), 10,47-RS 11.80 (1H, m)

ESI-MS (m/e): 442 [M+H]

Example 149:

2-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile

Specified in the title compound obtained as an oily substance in the same manner as in example 147, or in accordance with the method or by combining with an ordinary method but using 2-fluoro-benzonitrile.

1H NMR (CDCl3) δ: 1,50-2,49 (7H, m), 3.43 points-to 3.89 (2H, m), 5,10-of 5.34 (1H, m), 6,83-a 7.92 (8H, m), 8,31-8,42 (1H, m), 8,53-8,68 (1H, m), 10,80-11,23 (1H, m)

ESI-MS (m/e): 424[M+H]

Example 150:

2-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzamide

Specified in the title compound obtained as an oily substance in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 2-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)benzonitrile obtained in example 149.

1H NMR (CDCl3) δ: 1,52-2,46 (7H, m), 3,43-3,91 (2H, m), 5,10-the 5.51 (1H, m), of 5.99 (1H, users), 6,72-7,98 (8H, m), compared to 8.26-8,43 (2H, m), 8,59-to 8.70 (1H, m), of 10.58-10,94 (1H, m)

ESI-MS (m/e): 442[M+H]

Example 151:

1-(2-(6-(4-Nitro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 147, or under what about the way or Association with an ordinary method but using 4-fluoro-nitrobenzene.

1H NMR (CDCl3) δ: 1,40-of 2.50 (7H, m), 3,50-of 3.95 (2H, m), of 5.05-of 5.40 (1H, m), 7,00-7,80 (5H, m), 7,80-of 7.95 (1H, m), 8,15-8,30 (2H, m), 8,30-to 8.45 (1H, m), 8,60-to 8.70 (1H, m), or 10.60-11,00 (1H, m)

ESI-MS (m/e): 444[M+H]

Example 152:

1-(2-(2-Pyridin-2-yl-6-(4-(2H-tetrazol-5-yl)phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 60 and example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)benzonitrile obtained in example 147 (stage 1).

1H NMR (CDCl3) δ: 1,51-2,58 (7H, m), 3.43 points-are 3.90 (2H, M), 5,09-OF 5.55 (1H, m,), 6,73-7,60, 7,69-8,04, 8,29-8,69 ( 10H, each m)

ESI-MS (m/e): 467[M+H]

Example 153:

1-(2-(6-(4-(5-Methyl-[1,2,4]oxadiazol-3-yl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 61, example 64 example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-phenyl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)benzonitrile obtained in example 147 (stage 1).

1H NMR (CDCl3) δ: 1,49-2,7 (10H, m), 3,39-are 3.90 (2H, m), 5,17-5,52 (1H, m),6,26-8,89 (11N, m)

ESI-MS (m/e): 481[M+H]

Example 154:

3-(4-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)phenyl)-4H-[1,2,4]oxadiazol-5-he

Specified in the header of the connection will receive the same manner as in example 61 example 62 example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)benzonitrile obtained in example 147 (stage 1).

1H NMR (CDCl3) δ: 1,82-2,47 (7H, m), 3,60-3,3,94 (2H, m), 5,24-5,43 (1H, m), 7,15-8,05 (8H, m), 8,23-8,31 (1H, m), 8,71-8,78 (1H, m)

ESI-MS (m/e): 483[M+H]

Example 155:

5-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-1,3-dihydro-benzimidazole-2-he

(Stage 1) preparation of 1-(2-(6-(3,4-dinitro-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

Specified in the title compound obtained as an oily material of red color in the same manner as in example 147 (stage 1), or in accordance with the method or by combining with an ordinary method but using 4-fluoro-1,2-dinitro-benzene.

1H NMR (CD3OD) δ: 1,80-to 2.57 (7H, m), 3,61-was 4.02 (2H, m), 5,27-the ceiling of 5.60 (1H, m), 6,77-of 7.60 (6H, m), to $ 7.91-of 8.06 (1H, m), 8.17-a of 8.33 (1H, m), 8,72 (1H, users)

ESI-MS (m/e): 455[M+H]

(Stage 2) Obtaining 1-(2-(6-(3,4-diamino-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-e is oxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

0,030 ml of hydrazine monohydrate and 20 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in ethanol (1 ml) 72 mg of 1-(2-(6-(3,4-dinitro-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone and the reaction liquid was stirred at room temperature for 2 hours. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure. The resulting residue is purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound as an oily substance brown.

(Stage 3) Obtain 5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)-1,3-dihydro-benzimidazole-2-it:

Specified in the title compound obtained as an oily brown substance in the same manner as in example 62, or in accordance with the method or by combining with an ordinary method but using 1-(2-(6-(3,4-diamino-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone.

(Stage 4) to Obtain 5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)-1,3-dihydro-benzimidazole-2-it:

Specified in the title compound obtained as an amorphous, washes the VA in the same way, as in example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1-(2-trimethylsilyl-ethoxymethyl)-1H-benzimidazole-5-yloxy)-1,3-dihydro-benzimidazole-2-it.

1H NMR (CDCl3) δ: 1,80-to 2.57 (7H, m), 3,61-was 4.02 (2H, m), 5,27-the ceiling of 5.60 (1H, m), 6,77-of 7.60 (6H, m), to $ 7.91-of 8.06 (1H, m), 8.17-a of 8.33 (1H, m), 8,72 (1H, users)

ESI-MS (m/e): 455[M+H]

Example 156:

1-(2-(6-(3H-Benzimidazole-5-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

19 mg of 1-(2-(6-(3,4-diamino-phenoxy)-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 155 (stage 2), dissolved in 1 ml of formic acid and the reaction liquid was stirred at 100°C for 2 hours. The reaction liquid is concentrated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], getting listed at the beginning of the connection.

1H NMR (CD3OD) δ: 1,80-2,2,55 (7H, m), 3,60-4,00 (2H, m), 5,33-5,69 (1H, m,), 7,00-7,80, 7,91-8,04, 8,16-8,30, 8,67-8,80 ( 10H, each m)

ESI-MS (m/e): 439[M+H]

Example 157:

1-(2-(6-(2-Methyl-3H-benzimidazole-5-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection receives the same way as the example 156, or in accordance with the method or by combining with an ordinary method, but using acetic acid.

1H NMR (CD3OD) δ: 1,69-2,63 (10H, m), 3,42-3,91 (2H, m), 5,20-5,64 (1H, m), 6,58-7,87 (9H, m), by 8.22-8,66 (2H, m)

ESI-MS (m/e): 453[M+H]

Example 158:

5-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyrimidine-2-carbonitrile

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 147, or in accordance with the method or by combining with an ordinary method but using 5-bromo-pyrimidine-2-carbonitrile.

1H NMR (CDCl3) δ: 1,81-to 2.40 (7H, m), 3,56-3,88 (2H, m), 5.08 to of 5.34 (1H, m), 6.75 in-of 7.70 (3H, m), 7,81-of 7.90 (1H, m), 8,33-8,63 (4H, m)

ESI-MS (m/e): 426[M+H]

Example 159:

5-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyrimidine-2-carboxamide

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyrimidine-2-carbonitrile obtained in example 158.

1H NMR (CDCl3) δ: 1,79-2,42 (7H, m), 3,60-are 3.90 (2H, m), 5,18 of 5.39 (1H, m), 6,99-7,71 (3H, m), 7,82-a 7.92 (1H, m), 8.34 per-8,42 (1H, m), 8,55-8,65 (3H, m)

ESI-MS (m/e): 444[M-H]

Example 160:

Ethyl 4-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-Benson Gasol-5-yloxy)benzoate

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 147, or in accordance with the method or by combining with an ordinary method, but using ethyl 4-perbenzoate.

1H NMR (CDCl3) δ: 1,24-of 1.41 (3H, m), 1.70 to of 2.38 (7H, m), 3,53-a 3.87 (2H, m), 4,32-to 4.41 (2H, m), 5,14-of 5.45 (1H, m), of 6.96-to 7.67 (5H, m), 7,82-to $ 7.91 (1H, m), 7,98-of 8.06 (2H, m), 8.34 per-8,43 (1H, m), 8,61-8,68 (1H, m)

ESI-MS (m/e): 471[M+H]

Example 161:

1-(2-(6-Penetrate-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of 1-(2-(6-penetrate-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

0,019 ml Diisopropylamine, of 27.6 mg of triphenylphosphine and to 0.011 ml of 2-phenyl-ethanol add accordingly to the solution in tetrahydrofuran (1 ml) 29,2 mg of 1-(2-(6-hydroxy-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 121 (step 10), and the reaction liquid is stirred for 6 hours at room temperature. 0,040 ml Diisopropylamine, 53,2 mg of triphenylphosphine and is 0.023 ml of 2-phenyl-ethanol add accordingly in the reaction liquid and the reaction liquid was stirred overnight at room temperature. Aqueous saturated sodium bicarbonate is added to the reaction liquid, and extracted it with ethyl acetate and the extract setmethodname magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), ethyl acetate), obtaining mentioned in the title compound as an oily substance brown.

(Stage 2) Obtaining 1-(2-(6-penetrate-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

Specified in the title compound obtained as an oily substance in the same manner as in example 121 (step 12), or in accordance with the method or by combining with an ordinary method but using 1-(2-(6-penetrate-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone.

1H NMR (CDCl3) δ: 1,59-2,23 (7H, m), 2,87-3,10, 3,50-3,86, 3,96-4,35 (6H, each m), 5,04-5,13, 5,46-5,57 (1H, each m), 6,53-of 7.55 (8H, m), to 7.77-7,89 (1H, m), 8,32-to 8.40 (1H, m), 8,54-8,65 (1H, m), of 10.73-11,14 (1H, m)

ESI-MS (m/e): 427[M+H]

Example 162:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of tert-butyl 2-(2-fluoro-5-nitro-phenyl)pyrrol-1-carboxylate:

1.1 g tetrakis-triphenylphosphine palladium and 4.2 g of sodium carbonate are added to a solution of 4.3 g of 3-bromo-4-fluoro-nitrobenzene and 5.0 g of 1-(tert-butoxycarbonyl)pyrrol-2-Bronevoy acid in a mixture of 130 ml of dimethoxyethane and 22 ml of water and the reaction liquid is heated overnight at boiling with education is important fridge. Aqueous saturated sodium bicarbonate is added to the reaction liquid, and extracted it with ethyl acetate. The organic layer is washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=20/1), getting mentioned in the title compound as an oily yellow substance.

(Stage 2) Obtain tert-butyl 2-((2-(4-methanesulfonyl-phenoxy)-5-nitro-phenyl)pyrrol-1-carboxylate:

to 3.38 g of potassium carbonate are added to a solution in dimethylformamide (20 ml) 2.5 g of tert-butyl 2-(2-fluoro-5-nitro-phenyl)pyrrol-1-carboxylate and 1.55 g of 4-methanesulfonyl-phenol and the reaction liquid was stirred at 100°C for 2 hours. After cooling, water is added to the reaction mass and extracted with ethyl acetate. The organic layer is washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=2/1)to give specified in the title compound in the form of solid light yellow color.

(Stage 3) to Obtain tert-bout the l 2-(5-amino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate:

1.0 g of a catalyst of 5% platinum on coal is added to 120 ml of solution in ethanol 2,87 g of tert-butyl 2-(2-(4-methanesulfonyl-phenoxy)-5-nitro-phenyl)pyrrol-1-carboxylate and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate), obtaining mentioned in the title compound in the form of a solid white color.

(Stage 4) to Obtain 1-(2-(5-amino-2-(4-methanesulfonyl-phenoxy)-phenyl)pyrrolidin-1-yl)-2,2,2-Cryptor-ethanone:

342 mg of powdered zinc and 650 mg of benzyl chloroformate added to a solution in benzene (25 ml) 1.51 g of tert-butyl 2-(5-amino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate and the reaction liquid was stirred overnight at room temperature. The reaction liquid was filtered through Celite and aqueous saturated sodium bicarbonate is added to the filtrate. It is extracted with ethyl acetate and the organic layer washed with water and saturated salt solution accordingly and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting crude product was dissolved in 20 ml of 4n hydrochloric acid/1,4-dioxane and reacciona the mass is stirred at room temperature for 3 hours. The reaction liquid is distilled under reduced pressure and the resulting crude product is dissolved in 30 ml of chloroform. Under ice cooling there is added 2 ml of pyridine and 0.5 ml of anhydride triperoxonane acid and the reaction liquid is stirred for 2 hours at room temperature. 1 n hydrochloric acid is added to the reaction liquid, and extracted with ethyl acetate. The organic layer is washed with water, aqueous saturated solution of sodium bicarbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 50 mg of catalyst 10% palladium on coal are added to a solution in methanol (100 ml) of the obtained crude product, and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to 1/3), getting mentioned in the title compound in the form of a solid white color.

(Stage 5) to Obtain 1-(2-(5-amino-2-(4-methanesulfonyl-phenoxy)-4-nitro-phenyl)pyrrolidin-1-yl)-2,2,2-Cryptor-ethanone:

153 mg of potassium nitrate are added to a solution in triperoxonane acid (2 ml) 588 mg of 1-(2-(5-amino-2-(4-methanesulfonyl-phenoxy)the dryer is l)pyrrolidin-1-yl)-2,2,2-Cryptor-ethanone and the reaction liquid was stirred overnight at room temperature. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid to neutralize it, and then it is extracted with ethyl acetate. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 6) Receiving 2,2,2-Cryptor-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

100 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in ethanol (10 ml) 521 mg of 1-(2-(5-amino-2-(4-methanesulfonyl-phenoxy)-4-nitro-phenyl)pyrrolidin-1-yl)-2,2,2-Cryptor-ethanone and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure to give crude product. 226 mg of pyridine-2-carboxaldehyde added to a solution in methanol (10 ml), 448 mg of the obtained crude product, and the reaction liquid was stirred overnight at 50°C. Water is added to the reaction liquid, and extracted with ethyl acetate. The organic layer is washed with water and saturated Rast is or salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=20/1), getting mentioned in the title compound in the form of a solid of light yellow color.

(Stage 7) to Obtain 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole:

500 mg of potassium carbonate are added to a solution of 375 mg of 2,2,2-Cryptor-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone in a mixture of 16 ml of methanol and 3 ml of water and the reaction liquid was stirred overnight at room temperature. The reaction liquid is distilled under reduced pressure, diluted with saturated aqueous sodium hydrogen carbonate added thereto, and then extracted with ethyl acetate. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol/aqueous ammonia=10/1/0,1), receiving specified in the title compound in the form of solid light yellow color.

(Stage 8) to Obtain 1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

0.003 ml is casnigo anhydride are added to a solution in methylene chloride (1 ml) 10 mg 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole and the reaction liquid was stirred at room temperature for 1 hour. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,60-to 2.40 (7H, m), 3.05, and is 3.08 (total 3H, each s), 3,52-are 3.90 (2H, m), 5,13 lower than the 5.37 (1H, m), 7,08-of 7.69 (5H, m), 7,83-of 7.97 (3H, m), 8,32-to 8.40 (1H, m), 8,61-to 8.70 (1H, m)

ESI-MS (m/e): 477[M+H]

Example 163:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer A and enantiomer B

230 mg of 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 162 (step 7), separated using a column for separating optical isomers (CHIRALPAK AD 2 cm ϕ× 25 L (Daicel Chemical), mobile phase: hexane/2-propanol/diethylamine=20/80/0,1, flow rate: 10 ml/min), the enantiomer A (retention time: 19,0 min) and enantiomer B (retention time: 32,2 min), each in the form of an oily yellow substance.

Example 164:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)acanon A

0.003 ml of acetic anhydride are added to a solution in methylene chloride (1 ml) 12 mg of enantiomer A of 1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 163, and reacciona the liquid was stirred at room temperature for 1 hour. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), receiving one chiral form specified in the connection header in the form of a solid white color.

1H NMR (CDCl3) δ: 1,60-to 2.40 (7H, m), 3.05, and is 3.08 (total 3H, each s), 3,52-are 3.90 (2H, m), 5,13 lower than the 5.37 (1H, m), 7,08-of 7.69 (5H, m), 7,83-of 7.97 (3H, m), 8,35-8,43 (1H, m), 8,61-to 8.70 (1H, m)

ESI-MS (m/e): 477[M+H]

The rate of rotation of the plane of polarization of light: [α]24D(c=0,100, ethanol)-46,9

Example 165:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon B

to 0.011 ml of acetic anhydride are added to a solution in methylene chloride (1 ml) 44 mg of enantiomer B of 1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 163, and the reaction liquid was stirred at room temperature for 1 hour. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), receiving one chiral form specified in the connection header in the form of a solid white color.

ESI-MS(m/e):477[M+H]

The rate of rotation of the plane of polarization of light: [α]24Ȋ D(c=0,100, ethanol)+47,7

Example 166:

2,2,2-Cryptor-1-(2-(6-(4-fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 162 (stage 2)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 4-terfenol.

1H NMR (CDCl3) δ: 1,96-of 2.21 (3H, m), 2,31 is 2.43 (1H, m), of 3.77-4,08 (2H, m), 5,47-5,70 (1H, m), 6,88-6,91 (1H, m), 7,00-was 7.08 (4H, m), 7,26-to 7.50 (2H, m), 7,82-a 7.85 (1H, m), 8,31-8,35 (1H, m), 8,57-8,61 (1H, m)

ESI-MS (m/e): 471[M+H]

Example 167:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 162 (stage 2)-(stage 8), or in accordance with the method or by combining with an ordinary method but using 4-terfenol.

1H NMR (CDCl3) δ: 1,83-2,03 (6H, m), 2,32-to 2.41 (1H, m), to 3.58-3,86 (2H, m), 5,26-to 5.57 (1H, m), of 6.96-7,06 (5H, m), 7.24 to to 7.35 (2H, m), 7,80-7,88 (1H, m), 8,30-of 8.37 (1H, m), 8,56-to 8.62 (1H, m)

ESI-MS (m/e): 417[M+H]

Example 168:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-hydroxy-alanon

4.5 mg of glycolic acid, 12,3 mg, hydrate, N-hydroxybenzotriazole and 15.4 mg of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide add accordingly to the solution of chloroform is e (1 ml) 20 mg 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole, obtained in the same manner as in example 162 (stage 2)-(stage 7), but using 4-terfenol, and the reaction liquid was stirred overnight at room temperature. The reaction solvent is evaporated and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)to give specified in the header of the connection.

1H NMR (CDCl3) δ: 1,88-to 2.13 (3H, m), 2,20 is 2.43 (1H, m), 3,40-is 4.21 (4H, m), 5,14-the ceiling of 5.60 (1H, m), 6,85-rate of 7.54 (7H, m), 7,78-7,86 (1H, m), 8,29-of 8.37 (1H, m), 8,56-8,61 (1H, m)

ESI-MS (m/e): 433[M+H]

Example 169:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-methoxy-alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method but using methoxybutanol acid.

1H NMR (CDCl3) δ: 1,80-to 2.41 (4H, m), 3,26-of 3.46 (3H, m), 3,52-4,16 (4H, m), 5,28-the ceiling of 5.60 (1H, m), 6,79-EUR 7.57 (7H, m), to 7.77-a 7.85 (1H, m), 8,28 is 8.38 (1H, m), 8,56-to 8.62 (1H, m)

ESI-MS (m/e): 447 [M+H]

Example 170:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-3-phenyl-propane-1-he

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method, but using the-W 3-phenyl-propionic acid.

1H NMR (CDCl3) δ: 1,82-3,03 (8H, m), 3,48-3,93 (2H, m), 5,13 of 5.99 (1H, m), 6,82-of 7.60 (12H, m), 7,80-was 7.08 (1H, m), 8,09-8,39 (1H, m), 8,56-8,66 (1H, m)

ESI-MS (m/e): 507[M+H]

Example 171:

2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl-(2R)pyrrolidin-2-yl-metano

of 13.8 mg of 1-tert-butoxycarbonyl-D-Proline, 12,3 mg, hydrate, N-hydroxybenzotriazole and 15.4 mg of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in chloroform (1 ml) 20 mg 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 168, and the reaction liquid was stirred overnight at room temperature. The reaction solvent is evaporated under reduced pressure and the resulting residue is dissolved in 1 ml of 4n hydrochloric acid in ethyl acetate and the reaction liquid was stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified by thin-layer chromatography (NH TCX plate (Fuji Silysia Chemical), chloroform/methanol=30/1), getting mentioned in the title compound as an oily substance.

1H NMR (CDCl3) δ: 0,82-4,00 (13H, m), 5,23-5,61 (1H, m), 6,82-to 7.59 (7H, m), 7,78-7,88 (1H, m), 8,32-8,39 (1H, m), 8,57-8,64 (1H, m)

ESI-MS (m/e): 472[M+H]

Example 172:

(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-(2S)pyrrolidin-2-yl-metano

Specified in the header of the connection which are square in form of oily substance in the same way, as in example 171, or in accordance with the method or by combining with an ordinary method but using 1-tert-butoxycarbonyl-L-Proline.

1H NMR (CDCl3) δ: 0,82-4,00 (13H, m), 5,23-5,61 (1H, m), 6,82-to 7.59 (7H, m), 7,78-7,88 (1H, m), 8.30 to-8,39 (1H, m), 8,57-8,64 (1H, m)

ESI-MS (m/e): 472[M+H]

Example 173:

2-Dimethylamino-1-(2-(6-(4-fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily substance in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method, but using the hydrochloride of N,N-dimethylglycine.

1H NMR (CDCl3) δ: 1,81-2.57 m (10H, m), was 2.76-of 3.96 (4H, m), 5,41-5,62 (1H, m), 6,94-7,37 (7H, m), 7,81-7,89 (1H, m), 8,33 is 8.38 (1H, m), 8,59-8,68 (1H, m)

ESI-MS (m/e): 460[M+H]

Example 174:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-propane-1-he

Specified in the title compound obtained as an oily substance in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method, but using propionic acid.

1H NMR (CDCl3) δ: 0,95-1,24 (3H, m), 1.70 to 2,60 (6H, m), 3,52-of 3.94 (2H, m), 5,24-5,62 (1H, m), 6.75 in-7,66 (7H, m), to 7.77-a 7.92 (1H, m), 8,27-8,44 (1H, m), charged 8.52-8,68 (1H, m), 10,66-11,08 (1H, m)

ESI-MS (m/e): 431[M+H]

Example 175:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-l-yl)-butane-l-he

Specified the title compound obtained as an oily substance in the same way, as in example 168, or in accordance with the method or by combining with an ordinary method, but using n-butyric acid.

1H NMR (CDCl3) δ: 0,70-of 1.07 (3H, m), 1,40 is 2.44 (8H, m), 3,53-3,91 (2H, m), 5.25-in the ceiling of 5.60 (1H, m), 6,72-7,66 (7H, m), 7,80-to 7.93 (1H, m), 8.30 to-8,44 (1H, m), 8,53-8,68 (1H, m), is 10.68-11,18 (1H, m)

ESI-MS (m/e): 445 [M+H]

Example 176:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-3-hydroxy-propane-1-he

Specified in the title compound obtained as an oily substance in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method but using 3-hydroxypropionic acid.

1H NMR (CDCl3) δ: 1,43-by 2.73 (6H, m), 3,24-4,27 (5H, m), 5,24-the ceiling of 5.60 (1H, m), 6.75 in-of 7.60 (7H, m), 7,76-7,88 (1H, m), 8,27-to 8.40 (1H, m), 8,53-8,66 (1H, m), 10,44-br11.01 (1H, m)

ESI-MS (m/e): 447[M+H]

Example 177:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-methylamino-alanon

Specified in the header of the connection will receive the same manner as in example 171, or in accordance with the method or by combining with an ordinary method, but using N-tert-butoxycarbonyl-N-methylglycine.

1H NMR (CDCl3) δ: 1,82 is 2.01 (3H, m), 2,43-of 2.56 (4H, m), 3.25 to to 4.15 (4H, m), 5,32 lower than the 5.37 (1H, m), 7,00-7,31 (4H, m), 7,38-7,58 (2H, m), 8,03-8,08 (1H, m), of 8.37-8,43 (1H, m), 8,69-8,79 (1H, m), 8,80-to 8.94 (1H, m)

ESI-MS (m/e): 446[M+H]

Example 178:

5-(4-Fluoro-phenoxy)-6-(1-methanesulfonyl-pyrrolidin-2-yl)-2-p is ridin-2-yl-1H-benzimidazole

0.01 ml of triethylamine and 0.005 ml of methanesulfonanilide added to the solution in ethyl acetate (1 ml) 20 mg 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 168, and the reaction liquid was stirred overnight at room temperature. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,80-of 2.08 (3H, m), 2,28-to 2.42 (1H, m), 2,81 and 2,84 (total 13H, each s), 3,47-3,74 (2H, m), 5.17 to lower than the 5.37 (1H, m), 6,79-to 7.93 (8H, m), 8,30-of 8.37 (1H, m), 8,57-8,61 (1H, m)

ESI-MS (m/e): 453[M+H]

Example 179:

5-(4-Fluoro-phenoxy)-2-pyridin-2-yl-6-(1-pyrimidine-2-yl-pyrrolidin-2-yl)-1H-benzimidazole

of 0.013 ml of triethylamine and 6.3 mg of 2-chloro-pyrimidine are added to a solution in ethanol (2 ml) of 17.1 mg of 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 168, and the reaction liquid is heated at the boil under reflux for 3 hours. The reaction solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], obtained fraction was diluted with the with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,98-of 2.15 (3H, m), 2,34-to 2.42 (1H, m), 3,68-of 3.78 (1H, m), 3,90-4,07 (1H, m), 5,63 (1H, d, J=8.0 Hz), to 6.43 (1H, users), 6,87-of 7.55 (7H, m), 7,79-to 7.84 (1H, m), 8,15-to 8.34 (3H, m), 8,55-8,58 (1H, m)

ESI-MS (m/e): 453[M+H]

Example 180:

2-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ndimethylacetamide

11.4 mg of potassium carbonate and 11.1 mg iodated added to the solution in acetonitrile (1 ml) 20 mg 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 168, and the reaction liquid was stirred overnight at room temperature. The reaction liquid is concentrated and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining specified in the header of the connection in view of the solid white color.

1H NMR (CDCl3) δ: 1,60-2,04 (3H, m), 2,20-to 2.13 (1H, m), 2,80-to 2.85 (1H, m), 3,37-3,44 (2H, m), 3.96 points-a 4.03 (1H, m), 5,41-5,52 (1H, m), 6.90 to-7,34 (5H, m), of 7.36-7,39 (1H, m), 7,65 and 8.00 (total 1H, each s), 7,83-7,87 (1H, m), at 8.36-8,39 (1H, m), 8,59-8,64 (1H, m)

ESI-MS (m/e): 432[M+H]

Example 181:

Ethyl 2-(6-(4-fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxylate

5.2 mg of powdered zinc and 0.006 ml ethylchloride added to a solution in benzene (1 ml) 20 mg 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 168, and the reaction liquid was stirred overnight at room temperature. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: of 1.23 to 1.31 (3H, m), 1,80-2,00 (3H, m), 2,20-2,39 (1H, m), 3,50-with 3.79 (2H, m), 3,91-4,17 (2H, m), 5,17 is 5.38 (1H, m), for 6.81-7,63 (7H, m), to 7.77-a 7.85 (1H, m), 8,28-8,39 (1H, m), 8,55-8,63 (1H, m)

ESI-MS (m/e): 447[M+H]

Example 182:

2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid

5 mg dimethylaminopyridine and 0,029 ml of trimethylsilyl isocyanate are added to a solution in methylene chloride (1 ml) of 17.1 mg of 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 162 (step 7, and the reaction liquid was stirred overnight at room temperature. Water added to the reaction liquid, and extracted with ethyl acetate and then washed with a saturated solution of salt. After drying and concentrating, the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], and the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,83-of 2.09 (3H, m), 2,22-to 2.40 (1H, m), of 3.07 (3H, s), 3,56-3,82 (2H, m), 4,35 and to 4.62 (total 2H, each users), 5,01-5,20 (1H, m), 7,08-of 7.95 (8H, m), 8.34 per-of 8.40 (1H, m), 8,62-8,64 (1H, m)

ESI-MS (m/e): 478[M+H]

Examples 183-1, 183-2:

2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid, enantiomer A and enantiomer B

10 mg of racemic 2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamide, obtained in example 182, share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/ethanol=20/80, the velocity of the flow: 10 ml/min), the enantiomer A (retention time: 17,9 min) and enantiomer B (retention time: 27,6 min), each in the form of a solid white color.

Enantiomer A:

ESI-MS(m/e):478[M+H]

The rate of rotation of the plane of polarization of light: [α]24D(c=0,100, ethanol)-27,4

Enantiomer B:

ESI-MS(m/e):478[M+H]

The rate of rotation of the plane of polarization of light: [α]24D(c=0,100, ethanol)+28,4

Example 184:

2-(6-(4-fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid

2 mg dimethylaminopyridine and 0,059 ml of trimethylsilyl isocyanate add accordingly to the solution in methylene chloride (1 ml) and 31.2 mg of 5-(4-fluoro-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 168, and the reaction liquid was stirred overnight at room temperature. Water added to the reaction liquid, and extracted with ethyl acetate and then washed with a saturated solution of salt. After drying and concentrating, the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,88-of 2.08 (3H, m), 2,32-2,48 (1H, m), 3,62-a 3.87 (2H, m), 4,34 and 4,71 (total 2H, each users), 5,15-and 5.30 (1H, m), 6,91-7,73 (7H, m), 7,81-7,87 (1H, m), 8,31-of 8.37 (1H, m), 8,59-8,61 (1H, m)

ESI-MS (m/e): 418[M+H]

Examples 185-1, 185-2:

2-(6-(4-Fluoro-dryer is XI)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid, enantiomer A and enantiomer B

9.0 mg of racemic 2-(6-(4-fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamide, obtained in example 184, share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ×25 L (Daicel Chemical), mobile phase: hexane/2-propanol=50/50, flow rate: 10 ml/min), the enantiomer A (retention time: 12,1 min) and enantiomer B (retention time: 26,9 min), each in the form of a solid white color.

Enantiomer A:

ESI-MS(m/e):418[M+H]

Enantiomer B:

ESI-MS(m/e):418[M+H]

Example 186:

2-(6-(4-Dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 162 (stage 2)-(stage 7) and example 182, or in accordance with the method or by combining with an ordinary method but using 4-hydroxy-N,N-dimethyl-benzamide.

1H NMR (CDCl3) δ: 1,85-2,07 (3H, m), 2,28 is 2.43 (1H, m), 3.00 and-3,18 (6H, m), 3,60-of 3.80 (2H, m), 5,10-5,23 (1H, m), 7,01-7,76 (7H, m), 7,83-7,88 (1H, m), 8,33-8,39 (1H, m), 8,63-8,64 (1H, m)

ESI-MS (m/e): 471[M+H]

Examples 187-1, 187-2:

2-(6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid, enantiomer A and enantiomer B

to 72.2 mg of racemic 2-(6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamide, poluchennogo is in example 186, share with columns for the separation of optical isomers (CHERALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/ethanol=40/60, flow rate: 10 ml/min), the enantiomer A (retention time: 18,1 min) and enantiomer B (retention time: 23,9 min), each in the form of a solid white color.

Enantiomer A:

ESI-MS(m/e):471[M+H]

Enantiomer B: ESI-MS(m/e):471 [M+H]

Example 188:

2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxylic acid ethyl amide

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 184, or in accordance with the method or by combining with an ordinary method but using utilizationof.

1H NMR (CDCl3) δ: 0,94-of 1.07 (3H, m), 1,80-2,03 (3H, m), 2,25-to 2.41 (1H, m), 3,10-3,26 (2H, m), 3,57-3,74 (2H, m), as 4.02-to 4.14 (1H, m), 5,07-5,23 (1H, m), 6,85-7,66 (7H, m), 7,78-a 7.85 (1H, m), 8,30 is 8.38 (1H, m), 8,54-8,63 (1H, m)

ESI-MS (m/e): 446[M+H]

Example 189:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 162 (step 6)-(stage 8), or in accordance with the method or by combining with an ordinary method, but using pyrazin-2-carboxaldehyde.

1H NMR (CDCl3) δ: 1,86-2,08 (7H, m), 3,37-are 3.90 (2H, m), 5,27-of 5.55 (1H, m), 6,76-to 7.64 (6H, m), 8,32-to 8.62 (2H, m), at 9.53-9,56 (1 is, m)

ESI-MS (m/e): 418[M+H]

Example 190:

1-(2-(6-(4-Fluoro-phenoxy)-2-thiazol-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 162 (step 6)-(stage 8), or in accordance with the method or by combining with an ordinary method but using thiazole-2-carboxaldehyde.

1H NMR (CDCl3) δ: 1,60-of 2.23 (6H, m), 2,24 is 2.43 (1H, m), 3,50-3,88 (2H, m), 5,28-to 5.57 (1H, m), 6,64 to 7.62 (7H, m), 7,89-7,94 (1H, m)

ESI-MS (m/e): 423[M+H]

Example 191:

(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)-methanol

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method, but using D,L-prolinol.

1H NMR (CDCl3) δ: 1,64-of 1.92 (3H, m), 1,97-to 2.06 (1H, m), 3.00 and-of 3.12 (1H, m), 3.04 from (3H, s), 3,38-of 3.46 (1H, m), 3,53-of 3.64 (2H, m), a-3.84 (1H, users), 6,98 (2H, d, J=8.6 Hz), 7,10 and 7,22 (total 1H, each s), 7,33-7,40 (1H, m), 7,50-EUR 7.57 (1H, m), 7,80-of 7.90 (3H, m), 8.34 per-to 8.41 (1H, m), 8,62-8,63 (1H, m)

ESI-MS (m/e): 465[M+H]

Example 192:

Methyl 1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxylate

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 15, or in accordance with the method, or merge the of with in the usual way, but using the hydrochloride of ester methyl D,L-Proline.

1H NMR (CDCl3) δ: 1,83-2,03 (3H, m), 2,20-of 2.28 (1H, m), 3,05 (3H, s), 3,20-3,86 (2H, m), of 3.54 (3H, s), 4,28-a 4.53 (1H, m), 6,91-7,37 (3H, m), 7,32-7,38 (2H, m), 7,81-7,87 (3H, m), 8.30 to-8,39 (1H, m), 8,61-to 8.62 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 193:

1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxylic acid methyl amide

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method, but using D,L-Proline methyl amide hydrochloride.

1H NMR (CDCl3) δ: 1,80-2,03 (3H, m), 2,25-to 2.40 (1H, m), 2,46 of $ 2.53 (3H, m), 3,06 (3H, s), 3,20-3,26 (1H, m), 3,60-of 3.78 (1H, m), 4,18-4,24 (1H, m), 7,02-of 7.60 (3H, m), 7,03 (2H, d, J=9.0 Hz), 7,82-a 7.92 (1H, m), 7,89 (2H,, d, J=9.0 Hz), 8,35 (1H, d, J=7,4 Hz), 8,63 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 492[M+H]

Example 194:

1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method, but using D,L-Proline amide hydrochloride.

1H NMR (CDCl3) δ: 1,91-2,03 (3H, m), 2.26 and costs 2.50 (1H, m), to 3.02 and 3.06 (total 3H, each s), 3,18 of 3.28 (1H, m), 3,63-3,91 (1H, m), 4,13-the 4.29 (1H, m), 6,04-6,33 (1H, m), 6,86-7,28 (4H, m), 7,37-7,41 (1H, m), of 7.48-,54 (1H, m), 7,80-a 7.92 (3H, m), 8.34 per is 8.38 (1H, m), 8,48-8,63 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 195:

1-(2-(6-(4-Fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-piperidine-1-yl)alanon

(Stage 1) preparation of 2-(2-fluoro-5-nitro-phenyl)pyridine:

0.55 g Tetrakis-triphenylphosphine palladium are added to a solution in 1,4-dioxane (20 ml) 2.1 g of 3-bromo-4-fluoro-nitrobenzene and 2.3 g of 2-trimethylamino-pyridine and the reaction liquid is heated overnight at boiling under reflux. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, and extracted with ethyl acetate. The organic layer is washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=7/1)to give specified in the title compound in the form of a solid yellow color.

(Stage 2) Obtaining 2-(2-(4-fluoro-phenoxy)-5-nitro-phenyl)pyridine:

713 mg of potassium carbonate are added to a solution in dimethylformamide (10 ml) 600 mg 4-fluoro-3-pyridylcarbinol and 347 mg of 4-fluoro-phenol and the reaction liquid was stirred at 100°C for 1 hour. After cooling, water is added to the reaction liquid, and extracted with ethyl acetate. The organic layer is washed with water and saturated RA is tworoom salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=5/1)to give specified in the title compound in the form of solid light yellow color.

(Stage 3) to Obtain tert-butyl (4-(4-fluoro-phenoxy)-3-pyridin-2-yl-phenyl)carbamate:

100 mg of the catalyst 10% palladium on coal are added to a solution in ethyl acetate (10 ml) 840 mg of 2-(2-(4-fluoro-phenoxy)-5-nitro-phenyl)pyridine and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure to give crude product,5 g of di-tert-butyl dicarbonate added to the solution in tetrahydrofuran (10 ml) of the obtained crude product, and the reaction liquid was stirred overnight at 60°C. the Reaction liquid is cooled, the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=10/1), getting mentioned in the title compound in the form of a solid white color.

(Stage 4) to Obtain 1-(2-(5-amino-2-(4-fluoro-phenoxy)-phenyl)piperidine-1-yl)ethanone:

0.3 ml of acetic anhydride and 100 mg of catalyst 10% palladium on coal are added to a solution in ethanol (20 ml) 300 mg of tert-is util (4-(4-fluoro-phenoxy)-3-pyridin-2-yl-phenyl)carbamate and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the filtrate is distilled under reduced pressure to give crude product. The resulting crude product is dissolved in 5 ml of 4n hydrochloric acid in 1,4-dioxane and the reaction liquid was stirred at room temperature for 1 hour. Aqueous saturated sodium bicarbonate is added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate), obtaining mentioned in the title compound in the form of a solid of light yellow color.

(Stage 5) to Obtain 1-(2-(5-amino-2-(4-fluoro-phenoxy)-4-nitro-phenyl)-piperidine-1-yl)ethanone:

64 mg of potassium nitrate are added to a solution in triperoxonane acid (1 ml) 190 mg of 1-(2-(5-amino-2-(4-fluoro-phenoxy)-phenyl)-piperidine-1-yl)ethanone and the reaction liquid was stirred overnight at room temperature. Aqueous saturated solution of sodium bicarbonate is added to reactions fluid to neutralize it, and then extracted with ethyl acetate. The organic layer was washed with a saturated solution of salt accordingly and dried b is wodnym sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 6) to Obtain 1-(2-(6-(4-fluoro-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)piperidine-1-yl)ethanone:

50 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in ethanol (10 ml) 180 mg of 1-(2-(5-amino-2-(4-fluoro-phenoxy)-4-nitro-phenyl)piperidine-1-yl)ethanone and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the filtrate is distilled under reduced pressure, getting 171 mg of crude product. 50 mg of the obtained crude product was dissolved in 1 ml of N-methylpyrrolidone and add 16 mg of pyridine-2-carboxaldehyde, the reaction liquid was stirred at room temperature for 3 days. Water added to the reaction liquid, and extracted with ethyl acetate and the organic layer washed with water and saturated salt solution accordingly and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of trifero Sosna acid], getting listed in the title compound in the form of a solid of light yellow color.

1H NMR (CDCl3) δ: 1,60-of 1.85 (3H, m), 1,92-2,09 (5H, m), 2,22-of 2.30 (1H, m), 3,50-of 3.78 (2H, m), 5,35 is 5.38 (1H, m), 6,94-was 7.08 (5H, m), 7,32-7,38 (2H, m), 7,84-7,89 (1H, m), 8,35 is 8.38 (1H, m), 8,62-8,67 (1H, m)

ESI-MS (m/e): 431[M+H]

Example 196:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate:

600 mg of the catalyst 10% palladium on coal are added to a solution in methanol (100 ml) x 6.15 g of 3-fluoro-4-hydroxyitraconazole and 930 mg of di-tert-butyl dicarbonate and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration, the solvent is evaporated and the residue is collected by filtration with a mixed solvent of ethyl acetate/hexane, getting listed at the beginning of the connection.

(Stage 2) Obtain tert-butyl (3-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)phenyl)carbamate:

of 4.00 g of 5-chloro-2-methanesulfonyl-pyridine and 8,80 g of cesium carbonate are added to a solution of N-methylpyrrolidinone (50 ml) 4,74 g of tert-butyl (3-fluoro-4-hydroxy-phenyl)carbamate obtained in (stage 1), and the reaction liquid was stirred at 100°C for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried soo what hatom sodium. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1)to give specified in the header of the connection.

(Stage 3) Obtain 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine:

and 0.98 g of potassium nitrate are added to a solution in triperoxonane acid (35 ml) to 3.38 g of tert-butyl (3-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)phenyl)carbamate obtained in (stage 2), the reaction liquid was stirred at room temperature for 1 hour and then the solvent is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/2)to give specified in the header of the connection.

(Stage 4) to Obtain 5-(2-cyano-phenoxy)-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine:

60 mg of 2-hydroxy-benzonitrile and 70 mg of potassium carbonate are added to a solution of N-methylpyrrolidinone (2 ml) 150 mg of 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in (stage 3), and reacciona the liquid was stirred at 90° C for 5 hours. Water added to the reaction liquid and the precipitate is collected by filtration, getting listed at the beginning of the connection.

(Stage 5) to Obtain 4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine:

20 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in methanol (5 ml) 161 mg of 5-(2-cyano-phenoxy)-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in (stage 4), and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration and the solvent is evaporated under reduced pressure, obtaining specified in the header of the connection.

(Stage 6) Receiving 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole:

0,007 ml of pyridine-2-carboxaldehyde and 0.5 ml of nitrobenzene are added to a solution in methanol (1 ml), 37 mg of 4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in (stage 5), and the reaction liquid was stirred overnight at 120°C. the Solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=20/1) and distributes thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the header of the connection is a solid brown color.

1H NMR (CD3OD) δ: 3,20 (3H, s)6,94 (1H, d, J=7.8 Hz), 7,22 (1H, t, J=7.8 Hz), 7,41-7,47 (1H, m), 7,47 (1H, t, J=7.8 Hz), 7,53 (1H, DD, J=7,8, and 2.3 Hz), 7,56-to 7.61 (1H, m), 7,66 (1H, d, J=7.8 Hz), 7,72 (1H, s), 7,78 (1H, s), of 8.04 (1H, d, J=7.8 Hz), compared to 8.26 (1H, d, J=2.3 Hz), 8,35 (1H, d, J=7.8 Hz), 8,80 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 484[M+H]

Example 197:

5-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

21 mg pyrazin-2-carboxylic acid, 52 mg of hydroxybenzotriazole and 52 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide of monohydride added to the solution in dimethylformamide (2 ml) 72 mg of 4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 196 (step 5), and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is dissolved in 1 ml N-methylpyrrolidinone and add to it 20 mg triftoratsetata ytterbium and the reaction liquid was stirred at 160°C for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried svodnyy sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=30/1) and distributes thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid brown color.

1H NMR (CD3OD) δ: 3,20 (3H, s), 6,93 (1H, d, J=7,6 Hz), 7,21 (1H, t, J=7,6 Hz), the 7.43 (1H, DD, J=8,6, and 2.3 Hz), 7,58 (1H, t, J=7,6 Hz), 7,66 (1H, d, J=7,6 Hz), to 7.67-of 7.90 (2H, m), 8,03 (1H, d, J=8.6 Hz), of 8.25 (1H, d, J=2.3 Hz), a total of 8.74 (1H, d, J=2.3 Hz), 8,81 (1H, d, J=2.3 Hz), at 9.53 (1H, s)

ESI-MS (m/e): 485[M+H]

Example 198:

5-(2-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole obtained in example 196.

1H NMR (CD3OD) δ: 3,23 (3H, s), 6,85-6,91 (1H, m), 7,17 (1H, t, J=7.8 Hz), 7,40 was 7.45 (2H, m), 7,53 (1H, DD, J=7,8, a 4.3 Hz), 7,55 for 7.78 (1H, m), 7,88 (1H, DD, J=7,8, and 2.3 Hz), to 7.99 (1H, d, J=8.6 Hz), 8,02 (1H, TD, J=7,8, and 2.3 Hz), of 8.27 (1H, d, J=2.3 Hz), a 8.34 (1H, d, J=7.8 Hz), 8,78 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 502[M+H]

Example 199:

5-(2-Carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-ILO is si)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole obtained in example 197.

1H NMR (CD3OD) δ: 3,22 (3H, s), 6.87 in-6,91 (1H, m), 7,15-7,22 (1H, m), 7,41-7,46 (2H, m), 7,51-a 7.85 (2H, m), 7,87 (1H, DD, J=7,8, and 2.3 Hz), to 7.99 (1H, d, J=7.8 Hz), 8,25-of 8.28 (1H, m), 8,73 is 8.75 (1H, m), 8,80-8,82 (1H, m), 9,51-9,54 (1H, m)

ESI-MS (m/e): 503[M+H]

Example 200:

5-(2-Fluoro-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3) and 2-terfenol.

1H NMR (CDCl3) δ: 3,20 (3H, s), 6,97? 7.04 baby mortality (1H, m), 7,05-to 7.15 (3H, m), 7,33 (1/2H, DD, J=8,8, 2,8 Hz), 7,34 (1/2H, DD, J=8,8, 2,8 Hz), of 7.36-7,42 (1H, m), 7,42 (1/2H, s), 7,70 (1/2H, s), 7,86-to $ 7.91 (1H, m), 7,99 (1/2H, d, J=8,8 Hz), 8,00 (1/2H, d, J=8,8 Hz), 8.34 per-of 8.40 (1H, m), 8,44 (1H, d, J=2,8 Hz), 8,61-8,65 (1H, m), 10,85 (1/2H, users), 10,96 (1/2H, users)

ESI-MS (m/e): 477[M+H]

Example 201:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified the title compound obtained as a colorless solid in the same way, as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-fluoro-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 200, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: is 3.21 (3H, s), 7,02-was 7.08 (1H, m), 7,09-7,17 (3H, m), 7,11 (1/2H, s), 7,34 (1/2H, DD, J=8,6, 2.7 Hz), was 7.36 (1/2H, DD, J=8,6, 2.7 Hz), 7,42 (1/2H, s), 7,43 (1/2H, s), 7,74 (1/2H, s), 8,01 (1/2H, d, J=8.6 Hz), 8,02 (1/2H, d, J=8.6 Hz), 8,46 (1H, d, J=2.7 Hz), 8,58 (1/2H, DD, J=2.7, and 1.6 Hz), 8,60 (1/2H, DD, J=2,7, l-6 Hz), 8,67 (1/2H, d, J=2.7 Hz), 8,68 (1/2H, d, J=2.7 Hz), 9,59 (1/2H, d, J=1.6 Hz), 9,62 (1/2H, d, J=1.6 Hz), 10,47 (1/2H, users), 10,61 (1/2H, users)

ESI-MS (m/e): 478[M+H]

Example 202:

5-(2-Fluoro-phenoxy)-2-(1H-pyrazole-3-yl)-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

3.9 mg 1H-pyrazole-3-carboxaldehyde added to the solution in dimethylformamide (0.5 ml) 15 mg 4-(2-fluoro-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 200, and the reaction liquid was stirred at 90°C for 30 minutes. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 3,20 (3H, s), 6,94-6,99 (1H, m), 7,01-to 7.15 (4H, m), 7,25-the 7.65 (2H, m), 7,31 (1H, DD, J=8,9, 2.7 Hz), 7,66 (1H, d, J=2.3 Hz), 7,98 (1H, d, J=8,9 Hz), 8,40 (1H, is, J=2.7 Hz)

ESI-MS (m/e): 466[M+H]

Example 203:

5-(2-Fluoro-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

4.3 mg of 1-methyl-1H-pyrazole-3-carboxylic acid, 6.0 mg of hydroxybenzotriazole and 8.5 mg monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to the solution in dimethylformamide (0.5 ml) 15 mg 4-(2-fluoro-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 200, and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with chloroform, washed with water and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the obtained residue add 3 mg of p-toluensulfonate acid and the reaction liquid was stirred at 120°C for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with water and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 3,19 (3H, s), of 3.97 (3H, s), 6,94-7,00 (1H, m), 6,99 (1/2H, users), 7,00-7,14 (4H, m), 7,27-7,33 (1H, m), 7,30 (1/2H, users), 7,40 (1/2H, users), 7,46 (1H, d, J=2.4 Hz), 7,65 (1/2H, users), 7,98 (1H, d, J=8,8 is C), 8,42 (1H, d, J=2.7 Hz)

ESI-MS (m/e): 480[M+H]

Example 204:

5-(2-Chloro-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 4-(2-chlorophenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine:

Specified in the header of the connection will receive the same manner as in example 196 (stage 4)-(stage 5), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 2-chlorophenol.

(Stage 2) Obtain 5-(2-chloro-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole:

of 0.26 ml of 1 M methanolic solution of aniline and pyridine-2-carboxaldehyde (1/1) are added to a solution in methanol (1 ml) 35 mg 4-(2-chlorophenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in (stage 1), and the reaction liquid was stirred overnight at 60°C. the Solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and then dried with anhydrous sodium sulfate. The solvent of viparita the t under reduced pressure, getting listed in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: 3,17 (3H, s), 6,92 (1H, d, J=8.0 Hz), 7,07 (1H, t, J=8.0 Hz), 7,22 (1H, t, J=8.0 Hz), 7,26-7,66 (4H, m), 7,66-7,80 (1H, users), of 7.90-8,08 (2H, m), 8,29 (1H, d, J=8.0 Hz), 8,31 (1H, d, J=2.4 Hz), 8,72 (1H, s)

ESI-MS (m/e): 493[M+H]

Example 205:

5-(2-Chloro-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

15 mg methyl pyrazin-2-imidate (methyl ester pyrazin-2-carboxymethylate) and 0,0065 ml methanesulfonic acid are added to a solution of N-methylpyrrolidinone (0.5 ml) 38 mg of 4-(2-chloro-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 204 (stage 1), and the reaction liquid was stirred at 120°C for 20 minutes. The reaction liquid clear liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and then dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid yellow color.

1H NMR (CD3OD) δ: 3,20 (3H, s), 6,97 (1H, d, J=7.8 Hz), 7,11 (1H, t, J=7.8 Hz), 7,26 (1H, t, J=7.8 Hz), 7,42 (1H, d, J=7.8 Hz), of 7.48 (1H, DD, J=8,6, and 2.3 Hz), 7,60-782 (2H, m), 8,02 (1H, d, J=8.6 Hz), 8,35 (1H, d, J=2.3 Hz), 8,71 (1H, s), 8,77 (1H, s), 9,48 (1H, s)

ESI-MS (m/e): 494[M+H]

Example 206:

5-(2-Trifluoromethyl-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 2-triptoreline.

1H NMR (CD3OD) δ: 3,17 (3H, s), 6,93-6,98 (1H, m), 7,21 (1H, t, J=7.4 Hz), 7,40-7,8 l (6H, m), 7,97-with 8.05 (2H, m), 8,24-8,39 (2H, m), 8,73-8,87 (1H, m)

ESI-MS (m/e): 527[M+H]

Example 207:

5-(2-Trifluoromethyl-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 4-(2-trifluoromethyl-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 206, and methyl pyrazin-2-imidate.

1H NMR (CD3OD) δ: 3,17 (3H, s), 6,97 (1H, d, J=7.8 Hz), 7,22 (1H, t, J=7.8 Hz), 7,46 (1H, DD, J=8,6, and 2.3 Hz), 7,54 (1H, t, J=7.8 Hz), 7,44-of 7.60 (1H, m), the 7.65 (1H, d, J=7.8 Hz), 7,84-7,86 (1H, m), 8,01 (1H, d, J=8.6 Hz), 8,31 (1H, d, J=2.3 Hz), 8,73 (1H, d, J=2.3 Hz), 8,80 (1H, d, J=2,3 is C), to 9.50 (1H, s)

ESI-MS (m/e): 528[M+H]

Example 208:

5-(3-Trifluoromethyl-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 3-triptoreline.

1H NMR (CD3OD) δ: 3,20 (3H, s), 7,00-to 7.15 (2H, m), 7,37 (1H, d, J=7.8 Hz), 7,45-of 7.55 (3H, m), 7,66 (1H, d, J=10.0 Hz), 7,76 (1H, users), 7,99-of 8.04 (2H, m), 8.30 to-8,35 (2H, m), 8,77 (1H, d, J=2.7 Hz)

ESI-MS (m/e): 527[M+H]

Example 209:

5-(4-Trifluoromethyl-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 4-triptoreline.

1H NMR (CD3OD) δ: 3,20 (3H, s), 6,98 (2H, d, J=8.6 Hz), 7,46-to 7.77 (4H, m), 7,60 (2H, d, J=8.6 Hz), 8,00-of 8.04 (2H, m), 8,31 (1H, d, J=3.1 Hz), a 8.34 (1H, d, J=8,2 Hz), 8,78 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 527[M+H]

Example 210:

5-(2-Deformity-phenoxy)-2-pyridin-2-yl-6-(methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 2-deformational.

1H NMR (CD3OD) δ: 3,17 (3H, s)6,70 (1H, t, J=55,2 Hz), 6.87 in (1H, d, J=7,4 Hz), 7,18 (1H, t, J=7.4 Hz), 7,40-7,46 (2H, m), 7,50-to 7.59 (3H, m), to 7.59-of 7.82 (1H, m), 7,98-of 8.04 (2H, m), 8,27-8,35 (2H, m), 8,76 (1H, users)

ESI-MS (m/e): 509[M+H]

Example 211:

5-(2-Herperidin-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3)and 2-fluoro-pyridine-3-ol obtained according to the method described in Journal of Medicinal Chemistry, 1999, Vol.42, No. 12, pp.2251-2259.

1H NMR (CDCl3) δ: is 3.21 (3H, s), 7,11-7,17 (1H, m), 7,22 (1/2H, s), 7.29 trend was 7.36 (2H, m), 7.29 trend was 7.36 (1/2H, m), 7,40-the 7.43 (1H, s), 7,53 (1/2H, s), 7,72 (1/2H, s), 7,88-to 7.93 (1H, m), 7,93-of 7.96 (1H, m), 7,99-8,03 (1H, m), of 8.37-to 8.41 (2H, m), 8,65-8,67 (1H, m), 10,78 (1/2H, users), 10,82 (1/2H, users)

ESI-MS (m/e): 478[M+H]

Example 212:

5-(2-Herperidin-3 is hydroxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-fluoro-pyridine-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 211, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: is 3.21 (3H, s), 7,14-7,19 (1H, m), 7.23 percent (1/2H, s), 7,26-7,40 (2H, m), 7,46 (1/2H, s), 7,54 (1/2H, s), 7,56 (1/2H, s), of 7.96-8,00 (1H, m), 8,03 (1H, DD, J=8,6, 3,9 Hz), to 8.41 (1H, DD, J=2.7, and 1,6 Hz), to 8.62 (1H, DDD, J=4,7, 2.7, and 1.6 Hz), 8,69-8,71 (1H, m), 9,62 (1H, DD, J=6,3, 1,6 Hz), 10,48 (1/2H, users), 10,56 (1/2H, users)

ESI-MS (m/e): 479[M+H]

Example 213:

5-(2-Herperidin-3-yloxy)-2-(1H-pyrazole-3-yl)-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 202, or in accordance with the method or by combining with an ordinary method but using 4-(2-fluoro-pyridine-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 211, and 1H-pyrazole-3-carboxaldehyde.

1H NMR (CDCl3) δ: is 3.21 (3H, s), was 7.08 (1H, d, J=2.3 Hz), 7,09-7,19 (1H, m), 7,19-7,49 (4H, m), 7,71 (1H, d, J=2.3 Hz), 7,88-of 7.96 (1H, m), 7,97-8,03 (1H, m), at 8.36 (1H, d, J=2.7 Hz)

ESI-MS (m/e): 467[M+H]

Example 214:

5-(2-Herperidin-3-yloxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole/p>

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 4-(2-fluoro-pyridine-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 211, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: 3,20 (3H, s), of 4.00 (3H, s), 7,00 (1H, d, J=2.4 Hz), 7,10-7,16 (1H, m), 7,19 (1/2H, users), 7,26-7,33 (2H, m), 7,35 (1/2H, users), of 7.48 (1H, d, J=2.4 Hz), 7,52 (1/2H, users), to 7.67 (1/2H, users), to $ 7.91-7,94 (1H, m), of 8.00 (1H, d, J=8.6 Hz), of 8.37 (1H, d, J=2.5 Hz), 10,13 (1H, users)

ESI-MS (m/e): 481[M+H]

Example 215:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 2-deformedarse-pyridine-3-ol obtained in comparative example 2.

1H NMR (DMSO-d6) δ: 3,22 (3H, s), 7,19-7,27 (1H, m), 7,29-7,86 (6H, m), 7,95-8,07 (3H, m), 8,33-8,35 (1H, m), 8,45-8,48 (1H, m), 8,77 (1H, s),

ESI-MS (m/e): 526[M+H]

Example 216:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-feast of the Zin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 205, or in accordance with the method or by combining with an ordinary method but using 4-(2-deformedarse-pyridine-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 215, and methyl pyrazin-2-imidate.

1H NMR (DMSO-d6) δ: 3,20 (3H, s), 7,21 (1H, DD, J=7,8, and 4.9 Hz), 7,30-of 7.90 (4H, m), a 7.62 (1H, t, J=72,6 Hz), 7,94 (1H, d, J=8,8 Hz), of 7.97 (1H, d, J=4,8 Hz), to 8.45 (1H, d, J=2.7 Hz), 8,77-8,83 (2H, m), 9,48 (1H, s)

ESI-MS (m/e): 527[M+H]

Example 217:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-(1-methyl-1H-pyrazole-3-yl)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 4-(2-deformedarse-pyridine-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 215, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (DMSO-d6) δ: 3,22 (3H, s), of 4.00 (3H, s), to 6.88 (1H, d, J=2.2 Hz), 7,17-of 7.82 (6H, m), of 7.90-to 7.99 (3H, m), 8,42-to 8.45 (1H, m)

ESI-MS (m/e): 529[M+H]

Example 218:

5-(2-Cyano-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of 4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-5-(1-hydroxy-pyridi the-3-yloxy)phenylamine:

Specified in the header of the connection will receive the same manner as in example 196 (stage 4), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 1-oxy-pyridine-3-ol.

(Stage 2) Obtaining 4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-5-(2-cyano-pyridine-3-yloxy)phenylamine:

of 0.90 ml trimethylsilylmethyl and 0.90 ml of triethylamine are added to a solution in acetonitrile (6 ml) 216 mg of 4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-5-(1-oxy-pyridine-3-yloxy)phenylamine and the reaction liquid was stirred overnight with heating at boiling under reflux. The solvent is evaporated under reduced pressure and added 1,1,1,3,3,3-hexamethyldisilazane, the reaction liquid is stirred for 1 hour with heating at boiling under reflux. The reaction liquid is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=30/1), receiving specified in the header of the connection.

(Stage 3) Obtain 5-(2-cyano-3-yloxy)-6-(6-methanesulfonamido-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 196 (stage 5) (stage 6), or in compliance and by the way, or Association with an ordinary method but using 4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-5-(2-cyano-pyridine-3-yloxy)phenylamine.

1H NMR (CDCl3) δ: 3,22 (3/2H, s), 3,23 (3/2H, s), 7.18 in-of 7.23 (2H, m), 7,40-of 7.48 (2H, m)to 7.50 (1H, s), 7,76 for 7.78 (1H, m), to $ 7.91-of 7.95 (1H, m), 8,03-of 8.06 (1H, m), 8,20-8,23 (1H, m), of 8.37-8,44 (2H, m), 8,58-8,67 (1H, m), 11,04 (1H, users)

ESI-MS (m/e): 485[M+H]

Example 219:

5-(2-Cyano-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 218 (stage 3), and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: 3,23 (3/2H, s), 3,24 (3/2H, s), 7,21-7,26 (2H, m), 7,42-of 7.48 (1H, m), 7,55 (1H, d, J=1.2 Hz), 7,80 (1/2H, s), 7,82 (1/2H, s), 8,04 (1/2H, s), 8,06 (1/2H, s), 8,19-8,21 (1H, m), to 8.41 (1H, DD, J=4,5, 1.2 Hz), 8,65 (1H, DD, J=3,9, and 2.3 Hz), 8,73 (1H, d, J=2.3 Hz), 9,65 (1H, d, J=1.2 Hz), 10,99 (1H, users)

ESI-MS (m/e): 486[M+H]

Example 220:

5-(2-Cyano-3-yloxy)-2-(1H-pyrazole-3-yl)-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 202, or in accordance with the method or by combining with conventional SP is way but using 4-(2-cyano-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 218 (stage 3), and 1H-pyrazole-3-carboxaldehyde.

1H NMR (CDCl3) δ: 3,22 (3H, s), 7,12 (1H, d, J=2.3 Hz), 7,17-of 7.25 (2H, m), 7,40-of 7.48 (2H, m), 7,71-7,74 (1H, m), 7,72 (1H, d, J=2.3 Hz), 8,00-8,03 (1H, m), 8.17-a 8,21 (1H, m), scored 8.38-to 8.41 (1H, m)

ESI-MS (m/e): 474[M+H]

Example 221:

5-(2-Cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 3-fluoro-4-(6-econsultancy-pyridine-3-yloxy)phenylamine:

of 10.9 g of 5-chloro-2-econsultancy-pyridine and 1.6 g of cesium carbonate are added to a solution in dimethylformamide (150 ml) 10.0 g of tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in example 196 (step 1), and the reaction liquid was stirred at 100°C for 3 hours. The solvent is evaporated under reduced pressure, the residue was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/9)to give the crude product. The resulting crude product is dissolved in 4n hydrochloric acid in dioxane and stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure, the AI, the residue is diluted with chloroform, washed with water and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/9), receiving specified in the header of the connection.

(Stage 2) Obtain 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine:

3.8 g of potassium nitrate are added to a solution in triperoxonane acid (100 ml) and 10.5 g of 3-fluoro-4-(6-econsultancy-pyridine-3-yloxy)phenylamine and the reaction liquid is stirred for 1 hour at room temperature and the solvent is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/2)to give specified in the header of the connection.

(Stage 3) Obtain 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole:

60 mg of 2-hydroxy-benzonitrile and 70 mg of potassium carbonate are added to a solution of N-methylpyrrolidinone (3 ml) 150 mg of 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-FeNi the amine and the reaction liquid was stirred at 90° C for 5 hours. Water added to the reaction liquid and the precipitate is collected by filtration, receiving raw product mg of Raney Nickel with a developed surface and 0.12 ml of hydrazine monohydrate are added to a solution in methanol (5 ml) of the obtained crude product, and the reaction liquid is stirred for 1 hour. The catalyst was removed by filtration and the solvent is evaporated under reduced pressure, receiving 160 mg of crude product. 0,20 ml of 1 M methanolic solution of aniline and pyridine-2-carboxaldehyde (1/1) are added to a solution in methanol (3 ml) 35 mg of the obtained crude product, and the reaction liquid was stirred overnight at 80°C. the Solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound in the form of a solid yellow color.

1H NMR (CD3OD) δ: of 1.27 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7,4 Hz)6,91 (1H, d, J=7.8 Hz), 7,19 (1H, t, J=7.8 Hz), the 7.43 (1H, d, J=7.8 Hz), 7,50-of 7.60 (2H, m), 7,60-of 7.90 (3H, m), 7,99-of 8.04 (2H, m), compared to 8.26 (1H, s), to 8.34 (1H, d, J=7.8 Hz), 8,77 (1H, s)

ESI-MS (m/e): 498[M+H]

Example 222:

5-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same way as in example 205, or the compliance by the way, or Association with an ordinary method but using 4-(2-cyano-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 221 (step 3)and methyl pyrazin-2-imidate.

1H NMR (CD3OD) δ: of 1.28 (3H, t, J=7,6 Hz)to 3.38 (2H, square, J=7,6 Hz)6,94 (1H, d, J=7,6 Hz), 7,21 (1H, t, J=7,6 Hz), was 7.45 (1H, DD, J=8,6, 2.7 Hz), 7,58 (1H, TD, J=7,6, 1.8 Hz), 7,66 (1H, d, J=7,6 Hz), 7.68 per-of 7.90 (2H,, m), 8,03 (1H, d, J=8.6 Hz), of 8.28 (1H, d, J=2.7 Hz), the rate of 8.75 (1H, d, J=2.0 Hz), 8,82 (1H, DD, J=2.0 a, 1.2 Hz), 9,54 (1H, q,j=1.2 Hz)

ESI-MS (m/e): 499[M+H]

Example 223:

5-(2-Fluoro-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2)and 2-fluoro-phenol.

1H NMR (CD3OD) δ: 1,18-1,24 (3H, m), 3,02-3,4l (2H, m), 6,97-7,40 (5H, m), 7,47-to 7.77 (3H, m), of 7.96-of 8.04 (2H, m), 8,30 (1H, d, J=7.8 Hz), 8,39-8,42 (1H, m), 8,73-8,78 (1H, m)

ESI-MS (m/e): 491[M+H]

Example 224:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same way as in example 205, or in accordance with the method or by combining with the usual way, but with and the use of 4-(2-fluoro-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine, obtained in example 223, and methyl pyrazin-2-imidate.

1H NMR (CD3OD) δ: 1,22 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 7,52 (1H, DD, J=3.1 and 8.6 Hz), 7,00-7,80 (6H, m), of 8.04 (1H, d, J=8.6 Hz), 8,42 (1H, d, J=3.1 Hz), 8,72 (1H, s), 8,79 (1H, s), 9,49 (1H, s)

ESI-MS (m/e): 492[M+H]

Example 225:

5-(2-Fluoro-phenoxy)-2-(1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 202, or in accordance with the method or by combining with an ordinary method but using 4-(2-fluoro-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 223, and 1H-pyrazole-3-carboxaldehyde.

1H NMR (CD3OD) δ: 1,22 (3H, t, J=7.4 Hz), 3,30-of 3.42 (2H, m), to 6.88 (1H, d, J=1.6 Hz), 6,99? 7.04 baby mortality (1H, m), 7,07-7,20 (3H, m), 7,22-the 7.43 (1H, m), 7,49 (1H, DD, J=7,8, 3.1 Hz), 7,56-to 7.68 (1H, m), 7,83 (1H, d, J=1,6 Hz), 8,02 (1H, d, J=7.8 Hz), 8,39 (1H, d, J=3.1 Hz)

ESI-MS (m/e): 480[M+H]

Example 226:

5-(2,3-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 2,3-debtor-phenol.

1H I Is R (CDCl 3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 6,69 to 6.75 (1H, m), 6,91-7,02 (2H, m), 7,20 (1/2H, s), 7,27-7,34 (1H, m), 7,37-7,47 (1H, m), 7,41 (1/2H, s), 7,53 (1/2H, s), 7,72 (1/2H, ), 7,87-a 7.92 (1H, m), 8,00 (1/2H, d, J=8.7 Hz), 8,01 (1/2H, d, J=8.7 Hz), at 8.36-to 8.41 (1H, m), 8,42 (1H, d, J=2.7 Hz), 8,63-8,67 (1H, m), 10,75 (1/2H, users), 10,80 (1/2H, users)

ESI-MS (m/e): 509[M+H]

Example 227:

5-(2,3-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2,3-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 226, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.38 (1H, square, J=7,4 Hz), 3,39 (1H, square, J=7,4 Hz), 6,72-of 6.78 (1H, m), 6,92-7,05 (2H, m), 7,22 (1/2H, s), 7,33 (1/2H, DD, J=8,8, 2.7 Hz), 7,34 (1/2H, DD, J=8,8, 2.7 GHz), 7,45 (1/2H, s), 7,53 (1/2H, s)7,75 (1/2H, s), 01 (1/2H, d, J=8,8 Hz), 02 (1/2H, d, J=8,8 Hz), 43 (1H, d, J=2.7 Hz), 60 (1/2H, DD, J=2.5 and 1.6 Hz), 62 (1/2H, DD, J=2.5 a, L6 Hz), 69 (1/2H, d, J=2.5 Hz), 70 (1/2H, d, J=2.5 Hz), 61 (1/2H, d, J=1.6 Hz), 63 (1/2H, d, J=1.6 Hz), 52 (1/2H, users), to 10.62 (1/2H, users)

ESI-MS (m/e): 510[M+H]

Example 228:

5-(2,3-Debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the JV the way or Association with an ordinary method but using 4-(2,3-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 226, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 3,37 (1H, square, J=7,4 Hz)to 3.38 (1H, square, J=7,4 Hz), of 3.97 (2H, s), 3,98 (1H, s), of 6.65-6.75 in (l/3H, m), 6.87 in (1/2H, users), 6,89-7,01 (3H, m), 7,10-7,19 (1H, m), 7,26-7,38 (1H, m), 7,30 (1/2H, s), 7,45 (2/3H, d, J=2.3 Hz), 7,47 (l/3H, d, J=2.3 Hz), 7,50-7,53 (l/6H, m), 7,62-to 7.67 (1/2H, m), 7.95 is-with 8.05 (1H, m), 8,39 (l/3H, d, J=2.5 Hz), 8,54 (2/3H, d, J=2.5 Hz), 10,00-of 10.25 (1H, m)

ESI-MS (m/e): 512[M+H]

Example 229:

5-(2,4-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 2,4-debtor-phenol.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 3,37 (1H, square, J=7,4 Hz)to 3.38 (1H, square, J=7,4 Hz), for 6.81-to 6.95 (2H, m), 6,95-7,05 (1H, m), 7,06 (1/2H, s), 7,33 (1/2H, s), 7,32 (1/2H, DD, J=8,6, 2.7 Hz), 7,34 (1/2H, DD, J=8,6, 2.7 Hz), 7,37-7,41 (1H, m), 7,40 (1/2H, s), 7,70 (1/2H, s), 7,86-to $ 7.91 (1H, m), 8,00 (1/2H, d, J=8.6 Hz), 8,01 (1/2H, d, J=8.6 Hz), 8.34 per-8,39 (1H, m), 8,46 (1H, d, J=2.7 Hz), 8,62-8,67 (1H, m), 10,67 (1/2H, users), 10,76 (1/2H, users)

ESI-MS (m/e): 509[M+H]

Example 230:

5-(2,4-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-atonality the-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2,4-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 229, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7.4 Hz), to 3.38 (1H, square, J=7,4 Hz), 3,39 (1H, square, J=7,4 Hz), 6,82-to 6.95 (2H, m), 6,98-7,05 (1H, m), 7,08 (1/2H, s), 7,34 (1/2H, DD, J=8,6, 2.7 Hz), 7,35 (1/2H, DD, J=8,6, 2.7 GHz), 7,38 (1/2H, s), 7,44 (1/2H, s), 7,74 (1/2H, s), 8,02 (1/2H, d, J=8.6 Hz), 8,03 (1/2H, d, J=8.6 Hz), 8,46 (1/2H, d, J=2.7 Hz), of 8.47 (1/2H, d, J=2.7 Hz), 8,58 (1/2H, DD, J=2.7, and 1.6 Hz), at 8.60 (1/2H, DD, J=2.7, and 1.6 Hz), 8,67 (1/2H, d, J=2.7 Hz), 8,68 (1/2H, d, J=2.7 Hz), 9,59 (1/2H, d, J=1.6 Hz), being 9.61 (1/2H, d, J=1.6 Hz), 10,54 (1/2H, users), 10,69 (1/2H, users)

ESI-MS (m/e): 510[M+H]

Example 231:

5-(2,4-Debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 4-(2,4-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 229, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: of 1.28 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 3,98 (3H, s), 6,78-6,85 (1H, m), 6,85-6,93 (1H, m), 6,93-6,98 (1H, m), 6,93-6,98 (1/2H, m), of 6.99 (1H, d, J=2.3 Hz), 7,02 (1/2H, users), 7,27-7,34 (1H, m), of 7.36 (1/2H, users), 7,46 (1H, d, J=2.3 Hz), to 7.64 (1/2H, users), to 7.99 (1H, d, J=8.6 Hz), 8,43 (1H, d, J=2.7 Hz), 10,19 (1/2H, users), 10,29 (1/2H, users)

ESI-MS (m/e): 512[M+H]

Example 232:

5-(2,5-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 2.5-debtor-phenol.

1H NMR (CD3OD) δ: of 1.23 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 6,76-6,89 (2H, m), 7,15-7,24 (1H, m), 7,49-of 7.55 (3H, m), 7,71 (1H, s), 8,01 (1H, TD, J=7,4, and 2.3 Hz), of 8.04 (1H, d, J=7,4 Hz), 8,32 (1H, d, J=7,4 Hz), 8,40 (1H, d, J=2.3 Hz), 8,77 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 509[M+H]

Example 233:

5-(2,5-Debtor-phenoxy)-2-pyridine-1-oxido-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

7.5 mg of m-chloroperbenzoic acid are added to a solution in chloroform (1.5 ml) 7.5 mg of 5-(2,5-debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 232, and the reaction liquid was stirred at 45°C for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (MC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: of 1.23 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 6,78-of 6.90 (2H, m), 7,20 (1H, TD, J=9,8, 5,1 Hz), 7,52 (1H, DD, J=6,6, 3.1 Hz), 7,56 (1H, s), a 7.62 (1H, t, J=8,2 Hz), 7,73 (1H, t, J=8,2 Hz), 7,78 (1H, s), of 8.04 (1H, d, J=8,2 Hz), to 8.41 (1H, d, J=3.1 Hz), 8,51 (1H, d, J=6.6 Hz), 8,64 (1H, d, J=8,2 Hz)

ESI-MS (m/e): 525[M+H]

Example 234:

5-(2,5-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 4-(2,5-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 232, and methyl pyrazin-2-imidate.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=6.9 Hz), to 3.38 (2H, square, J=6.9 Hz), 6,77-6,91 (2H, m), 7,17-7,24 (1H, m), 7,51 (1H, s), 7,52 (1H, DD, J=7,4, a 4.3 Hz), 7,74 (1H, s), of 8.04 (1H, d, J=7,4 Hz), to 8.41 (1H, d, J=2.3 Hz), a total of 8.74 (1H, d, J=4.3 Hz), 8,80 (1H, DD, J=2,3, l-8 Hz), of 9.51 (1H, d, J=1,8 Hz)

ESI-MS (m/e): 510[M+H]

Example 235:

5-(2,6-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-this is sulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 2,6-debtor-phenol.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.38 (1H, square, J=7,4 Hz), 3,39 (1H, square, J=7,4 Hz), of 6.68-6.75 in (1/2H, m), 6.90 to-7,00 (2H, m), 7,12-7,26 (1H, m), 7,27-7,53 (3H, m), 7.68 per-7,72 (1/2H, m), 7,84-a 7.92 (1H, m), 7,98-of 8.04 (1H, m), 8,31-8,39 (1H, m), to 8.41 (1/2H, d, J=2.3 Hz), 8,56 (1/2H, d, J=2.3 Hz), 8,57-8,63 (1H, m), 10,59-10,88 (1H, m)

ESI-MS (m/e): 509[M+H]

Example 236:

5-(2,6-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2,6-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 235, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 3,38 (1/2H, square, J=7,4 Hz), 3,39 (1H, square, J=7,4 Hz), 3,40 (1/2H, square, J=7,4 Hz), 6.73 x-6,78 (1/2H, m), 6,93? 7.04 baby mortality (2H, m), 6,93? 7.04 baby mortality (1/2H, m), 7,14-7,20 (1/2H, m), 7,22 (1/4H, s), 7,31-7,42 (1H, m), 7,44 (1/4H, s), 7,45 (1/4H, s), 7,53 (1/4H, s), 7,74 (1/4H, s)7,75 (1/4H, s), 8,00-with 8.05 (1H, m), 8,43 (1/2H, d, J=2.7 Hz), 8,56 (1/4H, DD, J=2.5 a, 1,6 Hz), to 8.57 (1/2H, d, J=2.7 Hz), 8,59 (1/4H, DD, J=2.5 and 1.6 Hz) 8,60 (1/4H, DD, J=2.5 a, L6 Hz), 8,61 (1/4H, DD, J=2.5 and 1.6 Hz), 8,66 (1/4H, d, J=2.5 Hz), 8,67 (1/4H, d, J=2.5 Hz), 8,68 (1/4H, d, J=2.5 Hz), 8,69 (1/4H, d, J=2.5 Hz), 9,56 (1/4H, d, J=1.6 Hz), 9,60 (1/4H, d, J=1.6 Hz), being 9.61 (1/4H, d, J=1.6 Hz), 9,63 (1/4H, d, J=1.6 Hz), 10,36 (1/4H, users), 10,48 (1/4H, users), 10,51 (1/4H, users), 10,57 (1/4H, users)

ESI-MS (m/e): 510[M+H]

Example 237:

5-(2,6-Debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 4-(2,6-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 235, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), of 3.96 (3H, s), 6.87 in (1/2H, users), 6,93-to 7.00 (3H, m), 7,10-7,17 (1H, m), 7,18 (1/2H, s), 7,30 (1/2H, s), 7,32-7,40 (1H, m), 7,34 (1H, d, J=2,5 Hz), 7,63 (1/2H, users), 7,98-8,03 (1H, m), 8,54 (1H, d, J=2.7 Hz), 10,18 (1/2H, users), 10,35 (1/2H, users)

ESI-MS (m/e): 512[M+H]

Example 238:

5-(2-Triptoreline-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 196 (stage 4), (stage 5) and the sample 205, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-Piri is in 3-yloxy)-2-nitro-phenylamine, obtained in example 221 (step 2), and 2-triptoreline-phenol.

1H NMR (CDCl3) δ: of 1.27 (3H, t, J=7.4 Hz), 3,36, and 3,37 (total 2H, each square, J=7,4 Hz), 6,95-7,00 (1H, m), 7,12-7,46 (5H, m), 7,50 and 7,76 (total 1H, each s), 7,98 and 8.00 (total 1H, each d, J=8,8 Hz), to 8.41 (1H, d, J=2.7 Hz), 8,59-to 8.62 (1H, m), 8,68 (1H, d, J=2.4 Hz), and being 9.61 9,63 (total 1H, each d, J=1,6 Hz)

ESI-MS (m/e): 558[M+H]

Example 239:

5-(2-Herperidin-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2)and 2-fluoro-pyridine-3-ol.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 7,11-7,16 (1H, m), 7,24 (1/2H, s), 7,26-to 7.35 (2H, m), 7,41 was 7.45 (1H, m), 7,43 (1/2H, s), 7,55 (1/2H, s), 7,72 (1/2H, s), 7,88-7,94 (2H, m,), 7,99-8,03 (1H, m), scored 8.38-to 8.41 (2H, m), 8,65-8,67 (1H, m), 10,94 (1/2H, users), 10,98 (1/2H, users)

ESI-MS (m/e): 492 [M+H]

Example 240:

5-(2-Herperidin-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-herperidin-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine, obtained in example 239, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7.4 Hz), to 3.38 (1H, square, J=7,4 Hz), 3,39 (1H, square, J=7,4 Hz), 7,13-7,24 (1H, m), 7,24 (1/2H, s), 7,26-7,39 (2H, m), 7,47 (1/2H, s), 7,56 (1/2H, s), to 7.77 (1/2H, s), 7,95-8,05 (2H, m), 8,40 (1H, d, J=2.3 Hz), 7.62mm (1/2H, DD, J=2,4, L6 Hz), 8,63 (1/2H, DD, J=2,4, and 1.6 Hz), 8,70 (1/2H, d, J=2.4 Hz), 8,71 (1/2H, d, J=2.4 Hz), 9,62 (1/2H, d, J=1.6 Hz), 9,63 (1/2H, d, J=1,6 Hz), 10,45 (1/2H, users), 10,51 (1/2H, users)

ESI-MS (m/e): 493[M+H]

Example 241:

5-(2-Herperidin-3-yloxy)-2-(1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 202, or in accordance with the method or by combining with an ordinary method but using 4-(2-herperidin-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 239, and 1H-pyrazole-3-carboxaldehyde.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7,4 Hz), 7,07 (1H, d, J=2.7 Hz), 7,08-7,13 (1H, m), 7,20 (1/2H, users), 7,24-7,30 (2H, m), 7,34 (1/2H, users), 7,52 (1/2H, users), 7,65 (1/2H, users), 7,71 (1H, d, J=2.7 Hz), 7,88-a 7.92 (1H, m), to 7.99 (1H, d, J=8.6 Hz), with 8.33 (1H, d, J=2.7 Hz)

ESI-MS (m/e): 481[M+H]

Example 242:

5-(2-Chloropyridin-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance what about the way or Association with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2)and 2-chloro-pyridine-3-ol.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 7,14-7,20 (2H, m), 7,28 (1/2H, s), 7,20-7,31 (1H, m), 7,40-7,46 (1H, m), 7,46 (1/2H, s), 7,60 (1/2H, s), 7,76 (1/2H, s), 7,88-to 7.93 (1H, m,), 8,00 (1/2H, d, J=8.6 Hz), 8,01 (1/2H, d, J=8.6 Hz), 8,11-8,16 (1H, m), 8,31-8,35 (1H, m), scored 8.38-8,42 (1H, m), 8,64-8,68 (1H, m), 10,82-10,95 (1H, m)

ESI-MS (m/e): 508[M+H]

Example 243:

5-(2-Chloropyridin-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-chloropyridin-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 242, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7.4 Hz), 7.18 in-7,24 (2H, m), 7,30 (1/2H, s), 7,31 (1/2H, DD, J=8,6, 2.7 Hz), 7,32 (1/2H, DD, J=8,6, 2.7 Hz), 7,51 (1/2H, s), to 7.61 (1/2H, s), 7,81 (1/2H, s), 8,02 (1/2H, d, J=8.6 Hz), 8,04 (1/2H, d, J=8.6 Hz), 8,15-to 8.20 (1H, m), 8,35 (1/2H, d, J=2.7 Hz), at 8.36 (1/2H, d, J=2.7 Hz), 8,63 (1/2H, DD, J=2,3, and 1.6 Hz), 8,64 (1/2H, DD, J=2,3, L6 Hz), 8,72 (1/2H, d, J=2.3 Hz), 8,73 (1/2H, d, J=2.3 Hz), for 9.64 (1/2H, d, J=1.6 Hz), 9,65 (1/2H, d, J=1.6 Hz), or 10.60 (1/2H, users), is 10.68 (1/2H, users)

ESI-MS (m/e): 509[M+H]

Example 244:

5-(2-Chloropyridin-3-yloxy)-2-(1-methyl-1H-pyrazole--yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 4-(2-chloropyridin-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 242, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7,4 Hz)to 4.01 (3H, s), 7,01 (1H, d, J=2.3 Hz), 7,12-7,17 (2H, m), 7,26 (1H, DD, J=8,8, 2.7 Hz), 7,39 (1/2H, users), of 7.48 (1/2H, users), 7,49 (1H, d, J=2.3 Hz), 7,58 (1/2H, users), 7,69 (1/2H, users), to 7.99 (1H, d, J=8,8 Hz), 8,10-of 8.15 (1H, m), 8,31 (1H, d, J=2.7 Hz), 10,28 (1H, users)

ESI-MS (m/e): 511[M+H]

Example 245:

5-(2-Cyano-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 218, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 1-oxy-pyridine-3-ol.

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7,4 Hz), 7,12-7,26 (3H, m), 7,38 was 7.45 (2H, m), 7,45 (1/2H, s), 7,46 (1/2H, s), of 7.75 (1H, s), 7,89-7,94 (1H, m), 7,99-with 8.05 (1H, m), by 8.22 compared to 8.26 (1H, m), 8,39-8,43 (1H, m), 8,67-to 8.70 (1H, m), 10,88 (1H, users)

ESI-MS (m/e): 499[M+H]

Example 246:

5-(2-Cyano-3-yloxy)-6-(6-econsultancy-the feast of the Dean-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 245, and pyrazin-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,35 (3/2H, t, J=7.4 Hz), 1,37 (3/2H, t, J=7.4 Hz), to 3.38 (1H, square, J=7,4 Hz), 3,39 (1H, square, J=7,4 Hz), 7,19-7,26 (2H, m), 7,42-7,47 (1H, m), 7,53 (1/2H, s), 7,54 (1/2H, s), 7,80 (1/2H, C), 7,81 (1/2H, s), 8,04 (1/2H, d, J=8.6 Hz), 8,05 (1/2H, d, J=8.6 Hz), by 8.22-of 8.25 (1H, m), 8,40-8,43 (1H, m), 8,64-8,66 (1H, m), 8,73 (1H, d, J=2.5 Hz), 9,65 (1H, d, J=1.5 Hz), 10,87 (1/2H, users), 10,90 (1/2H, users)

ESI-MS (m/e): 500[M-H]

Example 247:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 2-deformedarse-pyridine-3-ol.

1H NMR (DMSO-d6) δ: of 1.10 (3H, t, J=7.4 Hz), to 3.36 (2H, square, J=7.4 Hz), 7.18 in-to 7.25 (1H, m), 7,31-7,87 (6H, m), 7,94-8,07 (3H, m), 8,32-at 8.36 (1H, m), 8,46-8,49 (1H, m), 8,77 (1H, s)

ESI-MS (m/e): 540[M+H]

Example 248:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(6-ethane is sulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 205, or in accordance with the method or by combining with an ordinary method but using 4-(2-deformedarse-pyridine-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 247, and methyl pyrazin-2-imidate.

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7,4 Hz), 7,07-7,11 (1H, m), 7,17 and 7,76 (total 1H, each s), 7,29-7,34 (2H, m), 7,37 (1H, t, J was 72.8 Hz), 7,46 (1H, s), of 7.96-8,03 (2H, m), 8,43 (1H, s), 8,60 and 8,62 (total 1H each s), 8,69 (1H, s), 9,60 and 9,63 (total 1H, each d, J=1.5 Hz)

ESI-MS (m/e): 541[M+H]

Example 249:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-(1-methyl-1H-pyrazole-3-yl)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 4-(2-deformedarse-pyridine-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 247, and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: of 1.10 (3H, t, J=7.4 Hz), to 3.36 (2H, square, J=7,4 Hz), of 4.00 (3H, s), to 6.88 (1H, d, J=2.3 Hz), 7,19 (1H, users), 7,26 to 7.75 (4H, m), 7,63 (1H, t, J=72,4 Hz), of 7.90-to 7.99 (3H, m), to 8.45 (1H, d, J=2.7 Hz)

ESI-MS (m/e): 543[M+H]

Example 250:

6-Benzyloxy-5-(2-pertenece)-2-pyrazin-2-yl-1H-Benz is midazol

(Stage 1) preparation of 4-benzyloxy-3-foronline:

only 2.91 ml of hydrazine monohydrate and about 1 g of the catalyst of Raney Nickel with a developed surface are added to a solution in methanol (60 ml) 4.94 g of 4-benzyloxy-3-peritrabecular and the reaction liquid was stirred at room temperature for 2 hours. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily yellow substance.

(Stage 2) Obtaining N-(4-benzyloxy-3-forfinal)pyrazinecarboxamide:

2,59 g pyrazin-2-carboxylic acid and 4.73 g of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (60 ml) of 4.13 g of 4-benzyloxy-3-foronline and the reaction liquid was stirred overnight at room temperature. The pyridine is evaporated under reduced pressure and then water is added. The precipitate is collected by filtration, getting mentioned in the title compound in the form of a solid brown color.

(Stage 3) Obtaining N-(4-benzyloxy-5-fluoro-2-nitrophenyl)pyrazinecarboxamide:

40 ml triperoxonane acid and 1.99 g of potassium nitrate is added to the suspension in chloroform (40 ml) 5,80 g of N-(4-benzyloxy-3-forfinal)pyrazinecarboxamide under ice cooling and the reaction liquid was stirred overnight at the room for the Noah temperature. The solvent is evaporated under reduced pressure and add aqueous saturated solution of sodium bicarbonate. The obtained solid substance was washed with a mixed solvent of ethyl acetate and hexane, obtaining mentioned in the title compound in the form of a solid yellow color.

(Stage 4) to Obtain N-(4-benzyloxy-5-(2-pertenece)-2-nitrophenyl)pyrazinecarboxamide:

0.54 ml of 2-terfenol and of 2.53 g of potassium carbonate are added to a solution in dimethylformamide (16 ml) and 2.14 g of N-(4-benzyloxy-5-fluoro-2-nitrophenyl)pyrazinecarboxamide and the reaction liquid was stirred at 90°C for 5 hours and then add water. The precipitate is collected by filtration, getting mentioned in the title compound in the form of a solid yellow color.

(Stage 5) to Obtain 5-benzyloxy-6-(2-pertenece)-2-pyrazin-2-yl-1H-benzimidazole:

and 3.72 g of dihydrate of tin chloride (II) are added to the suspension in dimethylformamide (16 ml) of 1.52 g of N-(4-benzyloxy-5-(2-pertenece)-2-nitrophenyl)pyrazinecarboxamide and the reaction liquid was stirred overnight at 80°C. the Reaction liquid was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is raybaut mixed solvent of ethyl acetate and hexane, getting listed in the title compound in the form of a solid yellow color.

1H NMR (DMSO-d6) δ: of 5.15 and 5.17 (total 2H, each s), 6,78-6,93 (1H, m), 7,06-7,40 (9H, m), 7,54 and EUR 7.57 (total 1H, each s), 8,73 and a total of 8.74 (total 1H, each s), 8,76-8,79 (1H, m), 9,43 and 9,44 (total 1H, each d, J=1,6 Hz)

ESI-MS (m/e): 413[M+H]

Example 251:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(2-cyano-pyrimidine-5-yloxy)-1H-benzimidazole

(Stage 1) preparation of 5-(2-pertenece)-6-hydroxy-2-pyrazin-2-yl-1H-benzimidazole:

500 mg of catalyst 20% palladium hydroxide on coal added to the suspension 697 mg of 5-benzyloxy-6-(2-pertenece)-2-pyrazin-2-yl-1H-benzimidazole obtained in example 250, 10 ml of methanol and 10 ml of tetrahydrofuran and the reaction liquid is stirred in hydrogen atmosphere at room temperature for 1 hour. The catalyst was removed by filtration through Celite, the solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: ethyl acetate), obtaining mentioned in the title compound in the form of a solid yellow color.

(Stage 2) Obtain 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(2-cyano-pyridine-5-yloxy)-1H-benzimidazole:

7,0 mg 5-bromo-2-cyano-pyrimidine and 15 mg of cesium carbonate are added to a solution of N-methylpyrrolidinone (0.5 ml) of 7.0 mg of 5-(2-pertenece)-6-hydroxy-2-pyrazin-2-yl-1H-benzimidazole obtained with the adiya's 1, and the reaction liquid was stirred at 90°C for 15 minutes. The reaction mixture was purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The obtained fraction was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as a colourless solid.

1H NMR (CD3OD) δ: 7,01-7,58 (5H, m), of 7.64-of 7.82 (1H, m), charged 8.52 (2H, s), 8,67 (1H, s), a total of 8.74 (1H, s), 9,44 (1H, s)

ESI-MS (m/e): 426[M+H]

Example 252:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-cyano-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 251 (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-(2-pertenece)-6-hydroxy-2-pyrazin-2-yl-1H-benzimidazole obtained in example 251 (stage 1)and 5-bromo-2-cyanopyridine.

1H NMR (CD3OD) δ: 7,01-7,30 (5H, m), 7,42 (1H, DD, J=8,6, 3.1 Hz), 7,55-to 7.77 (1H, m), 7,81 (1H, d, J=8.6 Hz), 8,39 (1H, d, J=3.1 Hz), 8,71 (1H, s), 8,77 (1H, s), for 9.47 (1H, s)

ESI-MS (m/e): 425[M+H]

Example 253:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-trifluoromethyl-pyridine-3-yloxy)-1H-benzimidazole

16 mg of 5-bromo-2-triform the Teal-pyridine, 50 mg of cesium carbonate and 10 mg of copper oxide (II) are added to a solution of N-methylpyrrolidinone (1 ml) 21 mg of 5-(2-pertenece)-6-hydroxy-2-pyrazin-2-yl-1H-benzimidazole obtained in example 251 (stage 1), and the reaction liquid was stirred at 130°C for 5 hours. The precipitate was separated by filtration and the solution clear liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The obtained fraction was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid brown color.

1H NMR (CD3OD) δ: 6,70-to 7.84 (6H, m), 7,49 (1H, DD, J=8,8 Hz, 2.8 Hz), 7,78 (1H, d, J=8,8 Hz), 8,39 (1H, d, J=2,8 Hz), 8,73 (1H, s), 8,80 (1H, s), 9,49 (1H, s)

ESI-MS (m/e): 468[M+H]

Example 254:

5-(2,6-Debtor-phenoxy)-4-fluoro-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 2,3-debtor-1-(6-methanesulfonyl-pyridine-3-yloxy)-4-nitrobenzene:

112 mg of 6-methanesulfonyl-pyridine-3-ol and 100 mg of potassium carbonate are added to a solution of N-methylpyrrolidinone (3 ml) 135 mg of 2,3,4-Cryptor-nitrobenzene, and the reaction liquid was stirred at 50°C for 1 hour. The reaction liquid was diluted with ethyl acetate, the item is washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1)to give specified in the header of the connection.

(Stage 2) Obtaining N-2,3-debtor-4-(6-methanesulfonyl-pyridine-3-yloxy)-6-nitro-phenyl)pyrazinecarboxamide:

0.2 ml of hydrazine monohydrate and about 0.01 g of Raney Nickel with a developed surface are added to a solution in methanol (3 ml) 22 mg of 2,3-debtor-1-(6-methanesulfonyl-pyridine-3-yloxy)-4-nitro-benzene and the reaction liquid was stirred at room temperature for 15 minutes. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure to give crude product. 12 mg pyrazin-2-carboxylic acid and 25 mg of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (1 ml) of the obtained crude product, and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product. 0.1 ml of fuming nitric acid are added to a solution in triperoxonane acid (2 ml) of the crude product and the reaction liquid is stirred the night at 45° C. the Solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1)to give specified in the header of the connection.

(Stage 3) Obtain 5-(2,6-debtor-phenoxy)-4-fluoro-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole:

8 mg of 2,6-differenoe and 8 mg of potassium carbonate are added to a solution of N-methylpyrrolidinone (0.5 ml) 8.6 mg N-(2,3-debtor-4-(6-methanesulfonyl-pyridine-3-yloxy)-6-nitro-phenyl)pyrazinecarboxamide and the reaction liquid was stirred at 90°C for 15 minutes. Add 75 mg of the dihydrate of tin chloride (II) and the reaction liquid was stirred overnight at 90°C. Additional 3 mg of n-toluensulfonate acid is added and the reaction liquid was stirred at 90°C for 2 hours. The precipitate is collected by filtration and purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid brown color.

1H NMR (D 3OD) δ: 3,22 (3H, s), 6,93-6,99 (2H, m), 7,01-7,10 (1H, m), 7,30 was 7.45 (1H, m), 7,47-7,5l (1H, m), 8,02 (1H, d, J=8.6 Hz), of 8.37 (1H, d, J=2.3 Hz), the rate of 8.75 (1H, d, J=2.3 Hz), 8,80 (1H, s), of 9.56 (1H, )

ESI-MS (m/e): 514[M+H]

Example 255:

5-(2,6-Debtor-phenoxy)-7-fluoro-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

(stage 1) preparation of 2,3-debtor-1-(2,6-debtor-phenoxy)-4-nitrobenzene:

470 mg of 2,6-debtor-phenol and 1.5 g of tetrabutylammonium bromide are added to a solution of N-methylpyrrolidinone (13 ml) 500 mg of 2,3,4-Cryptor-nitrobenzene, and the reaction liquid was stirred overnight at 130°C. the Reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=4/1)to give specified in the header of the connection.

(Stage 2) Obtain 5-(2,6-debtor-phenoxy)-7-fluoro-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole:

Specified in the title compound obtained as a solid substance of white color in the same way as in example 254 (stage 2), (stage 3), or in accordance with the method or by combining with an ordinary method, but using 2,3-debtor-1-(2,6-debtor-phenoxy)-4-nitro-benzene and 6-econsultancy-pyridine-3-ol, Paul is obtained in comparative example 4, accordingly.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz), 6,91-of 6.96 (1H, m), 7,14 (2H, t, J=8,4 Hz), 7,27-7,34 (1H, m), of 7.48-rate of 7.54 (1H, m), 7,63 (1H, DD, J=8,8, 2.7 Hz), to 7.99 (1H, t, J=7,6 Hz), 8,10 (1H, d, J=8,8 Hz), 8,31-of 8.37 (1H, m), 8,59 (1H, d, J=2.7 Hz), 8,70-8,76 (1H, m)

ESI-MS (m/e): 527[M+H]

Example 256:

5-(Pyridine-2-yloxy)-2-pyridin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 14, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, 2-hydroxypyridine.

1H NMR (CD3OD) δ: to 3.09 (3H, s), for 6.81 (1H, d, J=8,2 Hz), 7,02 (2H, d, J=8.6 Hz), 7,02-7,07 (1H, m), 7,49-rate of 7.54 (1H, m), 7,55 (1H, s), 7,63 (1H, s), 7,71-to 7.77 (1H, m), 7,83 (2H, d, J=8.6 Hz), 7,98-8,03 (2H, m), 8,31 (1H, d, J=7,6 Hz), 8,76 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 459[M+H]

Example 257:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 14, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and 2-deformedarse-pyridine-3-ol.

1H NMR (CD3OD) #x003B4; : 3,10 (3H, s), 7,05 (2H, d, J=8,4 Hz), 7,13-7,20 (1H, m), 7,33-of 7.70 (4H, m), of 7.48 (1H, t, J=72,8 Hz), 7,87 (2H, d, J=8,4 Hz), 7,92 (1H, d, J=4.5 Hz), 8,01 (1H, t, J=7.4 Hz), 8,32 (1H, d, J=7.8 Hz), 8,77 (1H, users)

ESI-MS (m/e): 525[M+H]

Example 258:

5-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 14, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, 1-methyl-2-oxo-1,2-dihydro-pyridine-3-ol.

1H NMR (CDCl3) δ: totaling 3.04 (3H, s), of 3.56 (3H, s), the 6.06 (1H, dt, J=7,0, 2.7 Hz), 6,84 (1/2H, d, J=7,4 Hz), 6,88 (1/2H, DD, J=7,4, 1.8 Hz), 7,05-to 7.15 (3H, m), 7,20 (1/2H, s), 7,28 (1/2H, d, J=1.2 Hz), 7,38 (1H, DD, J=6,6, a 4.7 Hz), 7,46 (1/2H, s), 7,60 (1/2H, s), 7,80-of 7.90 (3H, m), at 8.36 (1H, t, J=7.2 Hz), to 8.62 (1H, d, J=4.4 Hz)

ESI-MS (m/e): 489[M+H]

Example 259:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of 5-fluoro-4-(4-econsultancy-phenoxy)-2-nitro-phenylamine:

Specified in the header of the connection will receive the same manner as in example 14, or in accordance with the method or by combining with an ordinary method but using 6-econsultancy-pyridine-3-ol.

(Stage 2) Obtain 5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-Piri is in-2-yl-1H-benzimidazole:

Specified in the title compound obtained as solid light yellow color in the same manner as in example 14, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-econsultancy-phenoxy)-2-nitro-phenylamine and 2-deformedarse-pyridine-3-ol.

1H NMR (CD3OD) δ: of 1.20 (3H, t, J=7,4 Hz)and 3.15 (2H, square, J=7,4 Hz),? 7.04 baby mortality (2H, d, J=8,4 Hz), 7,06-to 7.15 (1H, m), 7,30-of 7.70 (4H, m), 7,46 (1H, t, J=72,9 Hz), 7,80 (2H, d, J=8,4 Hz), 7,89 (1H, d, J=4.3 Hz), to 7.99 (1H, t, J=7,7 Hz), 8,30 (1H, d, J=8.0 Hz), a total of 8.74 (1H, users)

ESI-MS (m/e): 539[M+H]

Example 260:

5-(2-Deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 197, or in accordance with the method or by combining with an ordinary method but using 4-(2-deformedarse-pyridine-3-yloxy)-5-(4-econsultancy-phenoxy)benzene-1,2-diamine obtained in example 259 (stage 2).

1H NMR (CDCl3) δ: of 1.27 and 1.28 (total 3H, each t, J=7.4 Hz), 3,09 and 3,10 (total 2H, each square, J=7,4 Hz), 6,98 and 6,99 (total 2H, each d, J=9.0 Hz),? 7.04 baby mortality-7,10 (1H, m), 7.23 percent and 7,42 (total 1H, each s), 7,25-7,30 (1H, m), of 7.36 and 7,37 (total 1H, each t, J=73,0 Hz), 7,52 and 7,73 (total 1H, each s), 7,80 and 7,81 (total 2H, each d, J=9.0 Hz), of 7.90-of 7.96 (1H, m), 8,58-8,63 (1H, m), 8,68 and 8,69 (total 1H, each d, J=2.4 Hz), and being 9.61 9,63 (total 1H, each d, J=1.5 Hz)

SI-MS (m/e): 540[M+H]

Example 261:

5-(2,4-Debtor-phenoxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 259, or in accordance with the method or by combining with an ordinary method but using 4-fluoro-5-(4-econsultancy-phenoxy)-2-nitro-phenylamine obtained in example 259 (stage 1), and 2,4-debtor-phenol.

1H NMR (CD3OD) δ: to 1.21 (3H, t, J=7.4 Hz), 3,19 (2H, square, J=7,4 Hz), 6.89 in-6,95 (1H, m), 7,01 for 7.12 (2H, m), 7,11 (2H, d, J=8,4 Hz), 7.23 percent-to 7.67 (3H, m), to 7.84 (2H, d, J=8,4 Hz), to 7.99 (1H, t, J=7.4 Hz), 8,29 (1H, d, J=8,2 Hz), the rate of 8.75 (1H, users)

ESI-MS (m/e): 508[M+H]

Example 262:

4-(1-Methyl-1H-imidazol-2-ylsulphonyl)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light brown color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 1-methyl-1H-imidazole-2-thiol and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: to 3.09 (6H, s), a 3.87 (3H, s), 6,69 (1H, s), 6,74 (1H, s), 6,79-6,89 (2H, m), 7,07 (2H, d, J=8,4 Hz), 7,16 (1H, d, J=2.0 Hz), 7,42 (2H, d, J=8,4 Hz), 7,53 (1H, t, J=7,6 Hz), to 7.64 (1H, d, J=2,0 Hz), 8,17 (1H, d, J=7,4 Hz)

ESI-MS (m/e): 471[M+H]

Example 263:

4-(Pyridine-2-ylsulphonyl)-6-(4-dimethylcarbamoyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Ukazannoi the title compound obtained as solids in a light brown colour in the same way, as in example 67 or in accordance with the method or by combining with an ordinary method but using pyridine-2-thiol and 4-hydroxy-N,N-dimethylbenzamide, as appropriate.

1H NMR (CDCl3) δ: 3,05 (3H, s)to 3.09 (3H, s), 6.90 to-was 7.08 (4H, m), 7,30-the 7.65 (6H, m), a 7.85 (1H, t, J=7.5 Hz), of 8.37 (1H, d, J=7.8 Hz), to 8.45 (1H, d, J=3,9 Hz), to 8.62 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 468[M+H]

Example 264:

4-(2,6-Debtor-phenoxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method, but using 2,6-debtor-phenol and 4-methanesulfonyl-phenol.

1H NMR (CD3OD) δ: 3,22 (3H, s), and 6.25 (1H, s), 7,16-7,24 (3H, m), 7,49-rate of 7.54 (1H, m), 7,60-7,66 (1H, m), 7,70 for 7.78 (1H, m), 7,95 (2H, d, J=8,4 Hz), 8,02 (1H, m), 8,40 (1H, d, J=4,7 Hz), to 8.70 (1H, d, J=2.3 Hz), 8,78 (1H, d, J=2.3 Hz)

ESI-MS (m/e): 494[M+H]

Example 265:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-it 4-methanesulfonyl-phenol, as appropriate.

1H NMR (CD3OD) δ: 3,10 (3H, s), 3,63 (3H, s), 6.35mm (1H, t, J=7,1 Hz), to 6.39 (1H, s),7,06 (1H, C)7,16 (2H, d, J=8.0 Hz), 7,34 (1H, d, J=7,2 Hz), 7,42-7,52 (1H, m), 7,53 (1H, DD, J=6,8, and 1.6 Hz), of 7.90 (2H, d, J=8.0 Hz), to $ 7.91-8,00 (1H, m), 8,28 is 8.38 (1H, m), 8,71 (1H, s)

ESI-MS (m/e): 489[M+H]

Example 266:

4-(2,6-Debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method, but using 2,6-debtor-phenol and 6-methanesulfonyl-pyridine-3-ol obtained in comparative example 3, as appropriate.

1H NMR (CD3OD) δ: 3,22 (3H, s), to 6.39 (1H, s), 7,16-7,24 (2H, m), 7,21 (1H, d, J=8.6 Hz), 7,32-7,40 (1H, m), 7,54-7,58 (1H, m), of 8.06 (1H, d, J=8.6 Hz), of 8.47 (1H, d, J=2.3 Hz), 8,72 (1H, d, J=2.3 Hz), 8,79 (1H, C)of 9.56 (1H, s)

ESI-MS (m/e): 496[M+H]

Example 267:

4-(2,6-Debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 196 (step 6), or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 266.

1H NMR (CD3OD) δ: of 3.32 (3H, s), 6,47 (1H, s), 7,19-7,26 (3H, m), 7,34-7,42 (1H, m), 7,56-7,63 (2H, m), 8,05-8,11 (2H, m), to 8.41 (1H, d, J=8.6 Hz), 8,48 (1H, d, J=2.3 Hz), 8,83 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 495[M+H]

Example 268:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pirati the-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method, but using 2,6-debtor-phenol and 6-econsultancy-pyridine-3-ol obtained in comparative example 4, as appropriate.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 6,38 (1H, s), 7,10-of 7.25 (3H, m), 7,32-7,40 (1H, m), 7,56 (1H, DD, J=8,6, and 2.3 Hz), of 8.06 (1H, d, J=9.0 Hz), 8,48 (1H, d, J=2.7 Hz), 8,72 (1H, d, J=2.7 Hz), 8,79 (1H, s), of 9.56 (1H, s)

ESI-MS (m/e): 510[M+H]

Example 269:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 196 (step 6), or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 268.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 6,44 (1H, s), 7.18 in-to 7.25 (3H, m), 7,32-7,41 (1H, m), 7,55 to 7.62 (2H, m), 8,03-of 8.09 (2H, m), to 8.41 (1H, d, J=7.8 Hz), 8,49 (1H, d, J=2.3 Hz), 8,81 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 509[M+H]

Example 270:

4-(2-Fluoro-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 68, or in accordance with the method or by combining with an ordinary method, but using the m 2-fluoro-pyridine-3-ol and 6-methanesulfonyl-pyridine-3-ol accordingly.

1H NMR (DMSO-d6) δ: 3,23 (3H, s)6,09 (1H, d, J=2.3 Hz), 6.35mm (1H, d, J=2.3 Hz), 7,28 (1H, DD, J=7,8, and 5.5 Hz), to 7.59-to 7.61 (1H, m), 7,66-to 7.67 (1H, m), 7,84-a 7.85 (1H, m), of 8.06 (1H, d, J=8.6 Hz), 8,70-a total of 8.74 (1H, m), 8,87 (1H, d, J=2.3 Hz), to 9.15 (1H, d, J=1.6 Hz), 9,86 (1H, s)

ESI-MS (m/e): 479[M+H]

Examples 271, 272:

4-(2-Fluoro-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole and 4-(2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Listed in the connection header receives the same way as in examples 108-1 and 108-2, or in accordance with the method or by combining with an ordinary method but using 2-fluoro-pyridine-3-ol and 6-methanesulfonyl-pyridine-3-ol accordingly.

4-(2-Fluoro-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

1H NMR (CD3OD) δ: 3,23 (3H, s), to 6.19 (1H, d, J=2.3 Hz), 6,55 (1H, d, J=2.3 Hz), 7.23 percent (1H, DD, J=4.2, and 2.1 Hz), to 7.61-to 7.64 (2H, m), to 7.67 (1H, DD, J=8,6, 2.7 Hz), 7,84-a 7.85 (1H, m), 8,02 (1H, TD, J=7,8, and 1.6 Hz), 8,09 (1H, d, J=8.6 Hz), 8,16 (1H, d, J=7.8 Hz), 8,51 (1H, d, J=2.3 Hz), 8,68 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 478[M+H]

6-(6-Methanesulfonyl-pyridine-3-yloxy)-4-(2-oxo-1,2-dihydro-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

1H NMR (DMSO-d6) δ: of 3.25 (3H, s), 6,61-6,62 (2H, m), 6,97-7,00 (2H, m), 7,63-to 7.67 (2H, m), 8,02-8,11 (4H, m), 8,56 (1H, d, J=2.3 Hz), a total of 8.74 (1H, d, J=4,7 Hz), 10,33 (1H, s)

ESI-MS (m/e): 476[M+H]

Example 273:

4-(2-Fluoro-pyridine-3-yloxy)-6-(4-methanesulfonyl-phenoxy)-2-feast of the DIN-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 67 or in accordance with the method or by combining with an ordinary method but using 2-fluoro-pyridine-3-ol and 4-methanesulfonyl-phenol accordingly.

1H NMR (CD3OD) δ: 3,13 (3H, s), to 6.67 (1H, d, J=2.0 Hz), 7,21-of 7.25 (2H, m), 7,35-7,39 (2H, m), 7,60-7,63 (1H, m), to 7.77-of 7.82 (1H, m), 7,95-of 7.97 (2H, m), 8,00-of 8.09 (2H, m), at 8.36 (1H, d, J=8,2 Hz), 8,83 (1H, d, J=the 4.7 Hz)

ESI-MS (m/e): 477[M+H]

Example 274:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of 5-(4-econsultancy-phenoxy)-3-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)benzene-1,2-diamine:

Specified in the title compound obtained as an oily brown substance in the same manner as in example 67 (stage 1)-(stage 4), or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-it 4-econsultancy-phenol accordingly.

(Stage 2) Obtaining 4-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 204 (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-(4-econsult the Il-phenoxy)-3-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)benzene-1,2-diamine, obtained (stage 1).

1H NMR (CDCl3) δ: of 1.24 (3H, t, J=7.4 Hz), 3,21 (2H, square, J=7,4 Hz), the 3.65 (3H, s), 6,37 (1H, t, J=7.2 Hz), 6.42 per (1H, s), to 7.09 (1H, s), 7,20 (2H, d, J=8,8 Hz), 7,37 (1H, d, J=6.6 Hz), 7,46-rate of 7.54 (1H, m), 7,55 (1H, d, J=6.0 Hz), 7,88 (2H, d, J=8,8 Hz), 7,94-8,02 (1H, m), at 8.36 (1H, d, J=7,6 Hz), 8,73 (1H, s)

ESI-MS (m/e): 503[M+H]

Example 275:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-(propane-2-sulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 274, or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-it 4-(propane-2-sulfonyl)phenol.

1H NMR (CD3OD) δ: of 1.27 (6H, d, J=6.8 Hz), 3.27 to to 3.38 (1H, m), the 3.65 (3H, s), 6,37 (1H, t, J=7.4 Hz), 6.42 per (1H, s), 7,10 (1H, s), 7,20 (2H, d, J=8,8 Hz), 7,35-7,45 (1H, m), 7,47-rate of 7.54 (1H, m), 7,55 (1H, d, J=6,8 Hz), a 7.85 (2H, d, J=8,8 Hz), 7,27-8,03 (1H, m), 8,30-to 8.40 (1H, m), a total of 8.74 (1H, s)

ESI-MS (m/e): 517[M+H]

Example 276:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-(1H-pyrazole-3-yl)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 202, or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 268, and 1H-pyrazole-3-carboxaldehyde.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7 Hz), 3,37 (2H, square, J=7,4 Hz), 6,28-6,32 (1H, m), to 7.09 (1H, s), 7,19 (2H, t, J=8,2 Hz), 7,34 (1H, s), 7,52 (1H, t, J=4.5 Hz), 7,83 (1H, s), of 8.04 (1H, d, J=8.6 Hz), 8,46 (1H, d, J=2.7 Hz)

ESI-MS (m/e): 498[M+H]

Example 277:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-N,N-dimethylaminomethyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 274, or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-she and 4-(N,N-dimethylaminomethyl)phenol.

1H NMR (DMSO-d6) δ: 2,58 (6H, s), of 3.48 (3H, s), 6,21 (1H, t, J=7,1 Hz), of 6.31 (1H, s)6,91 (1H, s), 7,16 (2H, d, J=8,8 Hz), 7,30 (1H, d, J=6.4 Hz), 7,52 (1H, DD, J=7,5, 5.7 Hz), 7,60 (1H, d, J=5,1 Hz), 7,71 (2H, d, J=8,8 Hz), to 7.99 (1H, TD, J=7,8, and 1.6 Hz), of 8.27 (1H, d, J=7.8 Hz), 8,73 (1H, d, J=4,6 Hz)

ESI-MS (m/e): 518[M+H]

Example 278:

4-(2-Chloro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

(Stage 1) preparation of 3-(2-chloro-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine:

Specified in the title compound obtained as an oily brown substance in the same manner as in example 67 (stage 1)-(stage 4), or in accordance with the method or by combining with an ordinary method but using 2-chloro-phenol and 6-econsultancy-pyridine-3-ol accordingly.

(Stage 2) Obtaining 4-(2-chloro-phenoxy)6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole:

Specified in the title compound obtained as a solid substance of white color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-(2-chloro-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in (stage 1).

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=6.9 Hz), 3,39 (2H, square, J=6.9 Hz), 6,28 (1H, d, J=2.0 Hz), 7,10-7,20 (1H, m), 7,28-7,3l (2H, m), 7,39-the 7.43 (1H, m), EUR 7.57 (2H, TD, J=8,3, 4,2 Hz), with 8.05 (1H, d, J=8.6 Hz), 8,48 (1H, d, J=2.7 Hz), 8,72 (1H, d, J=2.3 Hz), 8,79-8,80 (1H, m), 9,58 (1H, s)

ESI-MS (m/e): 508[M+H]

Example 279:

4-(2-Fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 278, or in accordance with the method or by combining with an ordinary method but using 2-fluoro-phenol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: 1,24 (3H, U=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 6,40 (1H, s), 7,10-7,20 (1H, m), 7,28-7,34 (4H, m), EUR 7.57 (1H, DD, J=8,6, 2.7 Hz), of 8.06 (1H, d, J=8.6 Hz), 8,48 (1H, d, J=2.7 Hz), 8,72 (1H, d, J=2.3 Hz), 8,79-8,80 (1H, m), of 9.56 (1H, s)

ESI-MS (m/e): 492 [M+H]

Example 280:

4-(2-Trifluoromethyl-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 278, or in accordance with the method or by combining with the usual way, what about using 2-trifluoromethyl-phenol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 6,50 (1H, d, J=2.0 Hz), 7,24 (2H, d, J=7.8 Hz), 7,38 (1H, t, J=7.8 Hz), to 7.59 (1H, DD, J=8,6, 2.7 Hz), to 7.64 (1H, t, J=7,6 Hz), 7,81 (1H, d, J=7,8 Hz), of 8.06 (1H, d, J=8.6 Hz), and 8.50 (1H, d, J=2.7 Hz), 8,71 (1H, d, J=2.3 Hz), 8,78-8,79 (1H, m), 9,54-of 9.55 (1H, m)

ESI-MS (m/e): 542[M+H]

Example 281:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-cyclopropanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 274, or in accordance with the method or by combining with an ordinary method but using 3-hydroxy-1-methyl-1H-pyridine-2-it 4-cyclopropanesulfonyl-phenol accordingly.

1H NMR (DMSO-d6) δ: 1,01-of 1.15 (4H, m), 2,81-2,90 (1H, m), 3,51 (3H, s), 6,24 (1H, J=7,0 Hz), 6.35mm (1H, d, J=2.0 Hz), to 6.95 (1H, d, J=2.0 Hz), 7,18 (2H, d, J=9.0 Hz), 7,33 (1H, DD, J=7,5, 1.8 Hz), 7,53-EUR 7.57 (1H, m), 7,63 (1H, DD, J=6,8, 1.8 Hz), 7,87 (2H, d, J=9.0 Hz), 8,02 (1H, TD, J=7,8, 1.8 Hz), 8,31 (1H, d, J=8.0 Hz), the rate of 8.75 (1H, d, J=4,1 Hz)

ESI-MS (m/e): 515[M+H]

Example 282:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-(1-methyl-pyrazole-3-yl)-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 268, and 1H--methyl-pyrazole-3-carboxylic acid.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz), 4,12 (3H, s), is 6.61 (1H, s), 7,19 (1H, d, J=2.3 Hz), 7,22 (1H, s), 7,25 (2H, DD, J=5,6, and 2.3 Hz), 7,37-the 7.43 (1H, m), a 7.62 (1H, DD, J=8,6, 2.7 GHz), to 7.93 (1H, d, J=2.3 Hz), 8,08-of 8.09 (1H, m), 8,51 (1H, d, J=2.3 Hz)

ESI-MS (m/e): 512[M+H]

Example 283:

4-(3-Trifluoromethyl-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 278, or in accordance with the method or by combining with an ordinary method but using 3-trifluoromethyl-phenol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), to 6.39 (1H, s), 7,25-7,37 (5H, m), EUR 7.57 (1H, DD, J=4,3, 2.2 Hz), of 8.06 (1H, d, J=8.6 Hz), 8,48 (1H, d, J=2.7 Hz), 8,72 (1H, d, J=2.7 Hz), 8,79 (1H, (C), of 9.56 (1H, s)

ESI-MS (m/e): 542[M+H]

Example 284:

4-(4-Trifluoromethyl-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 278, or in accordance with the method or by combining with an ordinary method but using 4-trifluoromethyl-phenol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), to 6.80 (1H, s), 7,32 (2H, d, J=8.6 Hz), 7,66-to 7.64 (1H, m), 7,72 (2H, d, J=8.6 Hz), 8,08 (1H, d, J=9.0 Hz), 8,54-8,56 (1H, m), 8,70-8,73 (1H, m), 8,78 (1H, s), 9,50 (1H, s)

ESI-MS (m/e): 542[M+H]

Example 285:

4-(2,3-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 278, or in accordance with the method or by combining with an ordinary method, but using 2,3-debtor-phenol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7,3 Hz), 3,40 (2H, square, J=7,3 Hz), 6,59 (1H, d, J=1.6 Hz), 7,12-to 7.18 (4H, m), 7,60 (1H, DD, J=9,0, 2.7 Hz), 8,07 (1H, DD, J=8,6, and 0.8 Hz), 8,51 (1H, d, J=2.3 Hz), 8,71 (1H, d, J=2.3 Hz), 8,79 (1H, DD, J=2.7, and 1.4 Hz), at 9.53 (1H, d, J=1,6 Hz)

ESI-MS (m/e): 510[M+H]

Example 286:

4-(2-Cyano-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 274, or in accordance with the method or by combining with an ordinary method but using 2-cyano-phenol and 6-methanesulfonyl-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: 3,23 (3H, s)6,86 (1H, d, J=2.0 Hz), 7,21 (1H, d, J=8,2 Hz), 7,33-7,37 (2H, m), 7,62-to 7.67 (3H, m), to 7.84 (1H, d, J=7.8 Hz), 8,04-8,11 (2H, m), at 8.36 (1H, d, J=7.8 Hz), 8,54 (1H, d, J=2.7 Hz), 8,82 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 484[M+H]

Example 287:

4-(2,4-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 274, or in accordance with the method or by combining conventional with the special but using 2,4-debtor-phenol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: a 1.11 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 6,51 (1H, d, J=2.0 Hz), 7,05-7,10 (2H, m), 7,37-7,39 (1H, m), 7,46-to 7.59 (3H, m), 7,98-8,02 (2H, m), compared to 8.26 (1H, d, J=7.8 Hz), 8,56 (1H, d, J=2,7 Hz), 8,73 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 509[M+H]

Example 288:

4-(Pyridine-2-ylsulphonyl)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 274, or in accordance with the method or by combining with an ordinary method but using pyridine-2-thiol and 6-methanesulfonyl-pyridine-3-ol accordingly.

1H NMR (CDCl3) δ: 3,22 (3H, s), 7,03 (1H, d, J=8.0 Hz), 7,06-7,10 (1H, m), 7,34 (1H, d, J=2.1 Hz), 7,37-7,41 (1H, m), the 7.43 (1H, DD, J=8,8, 2,8 Hz), 7,52 (1H, TD, J=7,8 and 2.2 Hz), to 7.64 (1H, d, J=2.1 Hz), 7,88 (1H, TD, J=7,8, 1.8 Hz), 8,03 (1H, d, J=8,8 Hz), 8,39 (1H, d, J=7.8 Hz), to 8.45 (1H, DD, J=4,9, 1.0 Hz), 8,51 (1H, d, J=2.3 Hz), 8,64 (1H, d, J=4,1 Hz)

ESI-MS (m/e): 476[M+H]

Example 289:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-5-fluoro-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 119, or in accordance with the method or by combining with an ordinary method, but using 2,6-debtor-phenol, 6-econsultancy-pyridine-3-ol and PI is Azin-2-carboxylic acid accordingly.

1H NMR (CDCl3) δ: 1.30 and 1.32 to (total 3H, each t, J=7.4 Hz), to 3.38 and 3.40 (total 2H, each square, J=7,4 Hz), of 6.96-7.03 is (2H, m), 7,10-7,20 (1H, m), 7,14 and 7,52 (total 1H, each d, J=6.0 Hz), 7,34 and 7,38 (total 1H, each DD, J=8,6, 2,8 Hz), 8,03 and 8,06 (total 1H, each d, J=8.6 Hz), 8,48 and charged 8.52 (total 1H, each d, J=2,8 Hz), 8,55-8,72 (2H, m), 9,38 and 9,62 (total 1H, each d, J=1.5 Hz)

ESI-MS (m/e): 528[M+H]

Example 290:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-5-fluoro-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 196 (step 6), or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-4-fluoro-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 289.

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 6,94-7,01 (2H, m),? 7.04 baby mortality is 7.50 (4H, m), 7,79-of 7.95 (1H, m), 7,99-8,07 (1H, m), 8,23 and of 8.37 (total 1H, each d, J=7,0 Hz), 8,48 (1H, s), 8,60-8,68 (1H, m)

ESI-MS (m/e): 527[M+H]

Example 291:

4-(2,6-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-5-fluoro-2-(1-methyl-1H-pyrazole-3-yl)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 203, or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-4-fluoro-5-(6-econsultancy-Piri is in 3-yloxy)benzene-1,2-diamine, obtained in example 289 and 1H-1-methyl-pyrazole-3-carboxylic acid.

1H NMR (CD3OD) δ: of 1.23 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), was 4.02 (3H, s)6,94 (1H, s), 7,01 for 7.12 (2H, m), 7,14-of 7.23 (1H, m), 7,29 (1H, d, J=5.4 Hz), 7,51 (1H, d, J=8.0 Hz), of 7.70 (1H, s), of 8.06 (1H, d, J=8.6 Hz), and 8.50 (1H, s)

ESI-MS (m/e): 530[M+H]

Example 292:

4-(2,6-Debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-5-fluoro-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solids in a light brown colour in the same way as in example 290, or in accordance with the method or by combining with an ordinary method, but using 2,6-debtor-phenol and 6-methanesulfonyl-pyridine-3-ol accordingly.

1H NMR (CDCl3) δ: is 3.21 (3H, s), 6,98 (2H, t, J=8.0 Hz), 7,05 is 7.50 (4H, m), 7,80-to 7.93 (1H, m), 8,03 (1H, t, J=8,8 Hz), 8,23 and of 8.37 (total 1H, each d, J=8,4 Hz), of 8.47 (1H, s), 8,61 and 8,67 (total 1H, each s)

ESI-MS (m/e): 513[M+H]

Example 293:

1-(2-(6-(4-(2-Hydroxy-ethyl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 4-bromophenethylamine alcohol.

1H NMR (CDCl3) δ: 1,05-2,90 (10H, m), 3.00 and is 4.45 (4H, m), 5,20-of 5.45 (1H, m), 6,80-of 7.70 (7H, m), a 7.85-of 7.95 (1H, m), 8,20-to 8.45 (1H, m), 8,50-8,80 (1H, m)

ESI-MS (m/e): 443[M+H]

Note the p 294:

1-(2-(6-(4-(5-Methyl-[1,3,4]oxadiazol-2-yl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a colorless oily substance by the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 2-(4-bromo-phenyl)-5-methyl-[1,3,4]oxadiazole.

1H NMR (CDCl3) δ: 1,40-2,80 (1 OH, m), 3,50-of 3.95 (2H, m), 5,10-of 5.50 (1H, m), 6.90 to-7,60 (5H, m), 7,82-8,10 (3H, m), 8,35-to 8.45 (1H, m), 8,60 is 8.75 (1H, m)

ESI-MS (m/e): 481[M+H]

Example 295:

1-(2-(6-(4-(2-Methyl-oxazol-5-yl)phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-(4-bromo-phenyl)-2-methyl-oxazole.

1H NMR (CDCl3) δ: 1,66-2,66 (10H, m), 3,53-of 3.94 (2H, m), to 5.21-to 5.57 (1H, m), 6,93-7,92 (9H, m), 8.30 to-8,69 (2H, m), 10,61-10,97 (1H, m)

ESI-MS (m/e): 480[M+H]

Example 296:

2-Hydroxy-1-(2-(6-(4-methanesulfonyl-1 phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method but using enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-Ben is imidazole, obtained in example 163.

1H NMR (CD3OD) δ: 1,84-of 2.16 (3H, m), 2,24 is 2.43 (1H, m), 3,12 3.14 (total 3H, each s), 3,49-4,24 (4H, m), 5,17 is 5.38 (1H, m), 7,20-7,58 (5H, m), 7,93-of 8.04 (3H, m), compared to 8.26-8.30 to (1H, m), 8,73 (1H, s)

ESI-MS (m/e): 493[M+H]

Examples 297, 298:

1-(2-(6-(6-Econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

1-(2-(6-(5-Chloro-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Listed in the connection header receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-chloro-2-econsultancy-pyridine.

1-(2-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

1H NMR (CDCl3) δ: of 1.00 to 1.34 (3H, m), 1,44-2,41 (7H, m), 3,11-to 3.89 (4H, m), of 5.05-vs. 5.47 (1H, m), 6.73 x-8,72 (9H, m), 10,89-11,47 (1H, m)

ESI-MS (m/e): 492[M+H]

1-(2-(6-(5-Chloro-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

1H NMR (CDCl3) δ: 1,51 is 2.33 (7H, m), 3,41-are 3.90 (2H, m), 5,03-of 5.45 (1H, m), 6,79-8,67 (9H, m), 10,80-11,00 (1H, m)

ESI-MS (m/e): 434[M+H]

Example 299:

5-(4-Methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole, enantiomer A and enantiomer B

(Stage 1) preparation of 2,2,2-Cryptor-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

14,5 mg pyrazin-2-carboxylic acid and 27.0 mg of monohydrochloride 1-(3-d is methylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (1 ml) 53 mg of 1-(2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)-phenyl)pyrrolidin-1-yl)-2,2,2-Cryptor-ethanone, obtained in example 162 (step 6), and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid was diluted with saturated salt solution and extracted with ethyl acetate. The organic layers are combined washed with aqueous saturated solution of ammonium chloride and aqueous saturated sodium hydrogen carbonate solution and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is dissolved in 1 ml of toluene. Add to 9.9 mg of the monohydrate of p-toluensulfonate acid and the reaction liquid was stirred at 120°C for 6 hours. After cooling, the reaction liquid was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound as an oily substance.

(Stage 2) Obtain 5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole:

55 mg of potassium carbonate are added to a solution of 40 mg of 2,2,2-Cryptor-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidone-1-yl)ethanone in a mixture of the C 1.6 ml of methanol and 0.4 ml of water and the reaction liquid was stirred overnight at room temperature. The reaction liquid is concentrated under reduced pressure and to the residue add aqueous saturated solution of ammonium chloride, then extracted with chloroform and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol/aqueous ammonia=90/10/1)to give specified in the title compound as an oily substance.

(Stage 3) to Obtain enantiomer A and enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole:

7.2 mg of 5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/ethanol/diethylamine=20/80/0,1, flow rate: 10 ml/min), the enantiomer A (retention time: 21,5 min) and enantiomer B (retention time: 25,3 min), each in the form of an oily yellow substance.

Example 300:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer A

Specified in the title compound obtained as an oily substance in the same manner as in example 164, or in accordance with the method or by combining with the usual way, but with the use of the enantiomers of A 5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole, obtained in example 299.

1H NMR (CDCl3) δ: 1,80-2,42 (7H, m), 3.00 and-to 3.09 (3H, m), 3,57-are 3.90 (2H, m), 5,10-5,43 (1H, m), 7,02-8,00 (6H, m), 8,57-8,73 (2H, m), of 9.55-9,48 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 301:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer B

Specified in the title compound obtained as an oily substance in the same manner as in example 164, or in accordance with the method or by combining with an ordinary method but using enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 299.

ESI-MS(m/e): 478 [M+H]

Example 302:

1-(2-(6-(6-(Propane-2-sulfonyl)pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same method as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-chloro-2-(propane-2-sulfonyl)pyridine.

1H NMR (CDCl3) δ: 1,11-of 1.40 (6H, m), 1.55V is 2.43 (7H, m), 3,54-to 3.89 (3H, m), 5,11-of 5.48 (1H, m), 6,67-8,72 (9H, m), 11,00-of 11.69 (1H, m)

ESI-MS (m/e): 506[M+H]

Example 303:

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-3-phenyl-propane-1-he

Specified in the title compound obtained as a colorless oily substance in the same manner as in example 296, or in accordance with the way the m or Association with an ordinary method but using 3-phenyl-propionic acid.

1H NMR (CDCl3) δ: 1,10-3,10 (11N, m), 3,40-4,00 (2H, m), 4,90-and 5.30 (1H, m), 6,80-8,00 (13H, m), 8,30-and 8.50 (1H, m), 8,60 is 8.75 (1H, m), 10,50-11,20 (1H, m)

ESI-MS (m7e): 567[M+H]

Example 304:

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-attention

0,010 ml of ethyl dithioacetate added to a solution in chloroform (1 ml) 20 mg of enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 163, and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,50 is 2.80 (7H, m)3,00-3,20 (3H, m), 3,60-and 4.40 (2H, m), and 5.30-of 5.50 (1H, m), 7,00-of 7.60 (5H, m), 7,80-of 8.00 (3H, m), 8,30-and 8.50 (1H, m), 8,60 is 8.75 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 305:

2-Fluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in segaloviciene get in the same way, as in example 168, or in accordance with the method or by combining with the usual way, but with the use of sodium fluoroacetate.

1H NMR (CDCl3) δ: 1,67-to 2.40 (4H, m), 3.00 and-3,13 (3H, m), 3,51-4,00 (2H, m), 4,48-of 5.06 (2H, m), 5,18-5,46 (1H, m), 7,02-of 7.69 (5H, m), 7,80-7,98 (3H, m), 8.34 per-8,44 (1H, m), 8,53-to 8.70 (1H, m), 10,82-11,12 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 306:

1-(2-(2-(5-Bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of 4-bromo-5-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine:

of 5.2 g of 4-methanesulfonyl-phenol and 5.7 g of potassium carbonate are added to a solution in N,N-dimethylformamide (50 ml) of 6.4 g of 4-bromo-5-fluoro-2-nitrophenylamino and the reaction liquid was stirred at 120°C for 3 hours. 200 ml of water is added to the reaction liquid, and the precipitated solid is collected by filtration and dried, obtaining mentioned in the title compound in the form of a solid brown color.

(Stage 2) Obtain tert-butyl 2-(4-amino-2-(4-methanesulfonyl-phenoxy)-5-nitro-phenyl)pyrrol-1-carboxylate:

7.9 g of 1-(tert-butoxycarbonyl)pyrrol-2-Bronevoy acid, 1.8 g of dichlorobistriphenylphosphine palladium, 50 ml of aqueous saturated solution of sodium carbonate and 50 ml of water are added to a solution in dimethoxyethane (100 ml) of 10.3 g of 4-bromo-5-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine and the reaction liquid is stirred in a nitrogen atmosphere at 80°C in those which begins 1 hour. After cooling, the reaction liquid is filtered through Celite, the filtrate diluted with ethyl acetate, washed with water and saturated salt solution accordingly and then dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1), getting mentioned in the title compound as an oily substance brown.

(Stage 3) to Obtain tert-butyl 2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate:

20 ml of water and 4 g of catalyst 5% PT on coal are added to a solution in 2-propanol (200 ml) 12 g of tert-butyl 2-(4-amino-2-(4-methanesulfonyl-phenoxy)-5-nitro-phenyl)pyrrol-1-carboxylate and the reaction liquid is stirred in a hydrogen atmosphere of 50 kgf/cm2at 70°C for 2 days. The catalyst was removed by filtration through Celite, the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting mentioned in the title compound as an oily material is dark brown.

(Stage 4) to Obtain 2-(5-bromo-pyridine-2-yl)-5-(4-methanesulfonyl-phenoxy)-6-pyrrolidin-2-yl-1H-benzimidazole:

220 mg of 5-bromopyridin-2-carboxylic sour the s and 260 mg of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (10 ml) 500 mg of tert-butyl 2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate and the reaction liquid is stirred at room temperature for 12 hours. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, the obtained residue is dissolved in 10 ml triperoxonane acid and the reaction liquid is heated at the boil under reflux for 3 hours. After cooling, the reaction liquid is distilled under reduced pressure and the obtained residue was diluted with chloroform and then alkalinized with a saturated aqueous solution of sodium bicarbonate is added to it. Then the organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol/aqueous ammonia=50/1/0,1), getting mentioned in the title compound as a colorless oily substance.

(Stage 5) to Obtain 1-(2-(2-(5-bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

0,050 ml of acetic anhydride are added to a solution in pyridine (2 ml) 220 mg of 2-(5-bromo-pyridine-2-yl)-5-(4-methanesulfonyl-phenoxy)-6-pyrrolidin-2-yl-1H-benzimidazole and the reaction liquid AC who're asked at room temperature for 30 minutes. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol/aqueous ammonia=50/1/0,1), receiving specified in the title compound in the form of solid light brown color.

1H NMR (CDCl3) δ: 1,60-to 2.40 (7H, m), 2,90 is 3.15 (3H, m), 3,50-are 3.90 (2H, m), of 5.05-of 5.50 (1H, m), 6,80-7,80 (4H, m), 7,80-with 8.05 (3H, m), 8,20-8,35 (1H, m), 8,60-8,80 (1H, m), 10,50-11,05 (1H, m)

ESI-MS (m/e): 555, 557[M+H]

Example 307:

1-(2-(2-(6-Fluoro-pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 306 (stage 4), (stage 5), or in accordance with the method or by combining with an ordinary method, but using tert-butyl 2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)-phenyl)pyrrolidin-1-carboxylate and 6-fluoro-pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,70-to 2.40 (7H, m), 2,98-3,11 (3H, m), 3,57-are 3.90 (2H, m), 5,07-5,51 (iH, m), for 6.81-8,32 (9H, m), at 10.64-11,36 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 308:

1-(2-(2-pyridin-2-yl-6-(6-trifluoromethyl-pyridine-3-yloxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance with which ETLO yellow color in the same way, as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-bromo-2-trifluoromethyl-pyridine.

1H NMR (CD3OD) δ: 1,89 and 2.14 (total 3H, each s), 1,90-of 2.20 (3H, m), 2,24-of 2.50 (1H, m), 3,63-3,99 (2H, m), 5,26-of 5.40 (1H, m), 7,34-7,63 (4H, m), 7,80-7,86 (1H, m), 7,94-8,02 (1H, m), 8,29-of 8.37 (1H, m), 8,58-8,59 (1H, m), 8,73-8,78 (1H, m)

ESI-MS (m/e): 468[M+H]

Example 309:

1-(2-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer A

(Stage 1) preparation of 1-(2-(4,5-diamino-2-benzyloxy-phenyl)pyrrolidin-1-yl)ethanone, enantiomer A and enantiomer B:

2.2 g of 1-(2-(4,5-diamino-2-benzyloxy-phenyl)pyrrolidin-1-yl)ethanone obtained in example 121 (step 8), separated using a column for separating optical isomers (CHIRALPAK AS 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/ethanol=30/70, flow rate: 15 ml/min), the enantiomer A (retention time: 11,43 min) and enantiomer B (retention time: 16,32 min), each in a solid black color.

(Stage 2) to Obtain enantiomer A of 1-(2-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

Specified in the title compound obtained as an oily substance in the same manner as in example 121 (step 9)-(stage 12), or in accordance with the method or by combining with an ordinary method but using Enan is imera A 1-(2-(4,5-diamino-2-benzyloxy-phenyl)pyrrolidin-1-yl)ethanone, obtained in example 309 (stage 1), and 5-chloro-2-methanesulfonyl-pyridine.

1H NMR (CDCl3) δ: 1,80-2,42 (7H, m), 3,16-of 3.27 (3H, m), 3,57-3,91 (2H, m), 5,14-of 5.34 (1H, m),? 7.04 baby mortality-8,10 (6H, m), 8,31-to 8.70 (3H, m), 10,59-10,94 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 310:

1-(2-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer B

Specified in the title compound obtained as an oily substance in the same manner as in example 309, or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of 1-(2-(4,5-diamino-2-benzyloxy-phenyl)pyrrolidin-1-yl)ethanone obtained in example 309 (stage 1).

ESI-MS(m/e): 478 [M+H]

Example 311:

(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)pyridin-2-yl-metano

Specified in the header of the connection will receive the same manner as in example 296, or in accordance with the method or by combining with an ordinary method but using enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 163, and pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,60-of 2.45 (4H, m), 2.91 in-to 3.09 (3H, m), 3,71-4,30 (2H, m), 5,44-the ceiling of 5.60 and 5,91-6,03 (total 1H, each m), 6,77-7,93 (11N, m), 8,10-8,66 (3H, m), 10,82-11,00 (1H, m)

ESI-MS (m/e): 540[M+H]

Example 312:

(2-Fluoro-phenyl)-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzoni the azole-5-yl)pyrrolidin-1-yl)methanon

Specified in the header of the connection will receive the same manner as in example 296, or in accordance with the method or by combining with an ordinary method but using enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 163, and 2-fermenting acid.

1H NMR (CDCl3) δ: 1,80 is 2.51 (4H, m), 2,90-is 3.08 (3H, m), 3,40-4,08 (2H, m), 4,91-5.02 and 5,46-the ceiling of 5.60 (total 1H, each m), 6,55-8,69 (15H, m)

ESI-MS (m/e): 557[M+H]

Example 313:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-pertenece)-2-isoxazol-3-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 189, or in accordance with the method or by combining with an ordinary method but using isoxazol-3-carbaldehyde.

1H NMR (CDCl3) δ: 1,80 is 2.46 (4H, m), 1,87 and 2.16 (total 3H, each s), to 3.58-3,88 (2H, m), 5,13-5,17 and 5,52-5,55 (total 1H, each m), 6,85-7,40 (7H, m), 8,56 (1H, s)

ESI-MS (m/e): 407[M+H]

Example 314:

5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile

Specified in the title compound obtained as a solid substance of white color in the same way as in example 309, or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of 1-(2-(4,5-diamino-2-benzyloxy-phenyl)pyrrolidin-1-yl)ethanone obtained in example 309 (stage 1), and 2-cyano-5-bromo-pyrid is on.

1H NMR (CDCl3) δ: 1,53-2,42 (7H, m), 3,40-3,50 (2H, m), 5,07-of 5.29 (1H, m), 7,00-7,94 (6H, m), 8,28-8,68 (3H, m), 11,00-to 11.52 (1H, m)

ESI-MS (m/e): 425[M+H]

Example 315:

Tert-butyl 2-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl-methyl-carbamate

Specified in the header of the connection will receive the same manner as in example 171, or in accordance with the method or by combining with an ordinary method but using enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 163, and N-tert-butoxycarbonyl-glycine.

1H NMR (CDCl3) δ: 1,20-1,69 (16H, m), was 2.76-3,12 (7H, m), 5,15-of 5.26 (1H, m), 7,00-7,44 (5H, m), 7,76-of 8.00 (4H, m), 8,28-to 8.40 (1H, m), 8,58-8,73 (1H, m)

ESI-MS (m/e): 606[M+H]

Example 316:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-methylamino-alanon

Specified in the header of the connection will receive the same manner as in example 171, or in accordance with the method or by combining with an ordinary method, but using tert-butyl (2-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)-methyl-carbamate obtained in example 315.

1H NMR (CDCl3) δ: 1,60-of 1.97 (4H, m), 2,20-of 2.46 (3H, m), 2,94-is 3.08 (5H, m), 3,19-are 3.90 (2H, m), 5,15-5,43 (1H, m), 7,08-the 7.65 (5H, m), 7,87-7,94 (3H, m), at 8.36 is 8.38 (1H, m)8,64 (1H, s)

ESI-MS (m/e): 506[M+H]

Example 317:

1-(2-(6-(4-Means hanil-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of tert-butyl 2-(6-(4-methanesulfonyl-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-carboxylate:

10.0 mg 1H-pyrazole-3-carboxaldehyde added to a solution in N,N-dimethylformamide (1 ml) is 49.0 mg of tert-butyl 2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate obtained in example 306 (stage 3), and the reaction liquid was stirred overnight at 90°C. After cooling, the reaction liquid was diluted with ethyl acetate, washed with a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound in the form of a solid brown color.

(Stage 2) Obtaining 1-(2-(6-(4-methanesulfonyl-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

49.2 mg of tert-butyl 2-(6-(4-methanesulfonyl-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-carboxylate was dissolved in 1 ml of 4n hydrochloric acid in dioxane and the reaction liquid was stirred at room temperature for 2 hours. The reaction solvent is evaporated under reduced pressure and a 0.012 ml of acetic anhydride is added to 2 ml in pyridine according to the scientists of the residue and stirred at room temperature for 30 minutes. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound in the form of a solid brown color.

1H NMR (CDCl3) δ: 1,53-of 2.38 (7H, m), 2,97-3,10 (3H, s), 3,39-3,99 (2H, m), 5,06-5,31 (1H, m), 6,80-8,04 (8H, m)

ESI-MS (m/e): 466[M+H]

Example 318:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same way as in example 306 (stage 4), (stage 5), or in accordance with the method or by combining with an ordinary method, but using tert-butyl 2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate obtained in example 306 (stage 3), and 1-methyl-1H-pyrazole-3-carboxylic acid.

1H NMR (CDCl3) δ: 1,70-2,37 (7H, m), 2,98-3, 11 (3H, m), 3,52-was 4.02 (5H, m), 5,04-5,43 (1H, m), 6,74-to 7.67 (6H, m), 7,79-of 7.97 (2H, m), 10,38-11,00 (1H, m)

ESI-MS (m/e): 480[M+H]

Example 319:

1-(2-(2-(5-fluoro-pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same way as in example 318, or in accordance with the method or by combining with the conventional method, the nose using 5-fluoro-pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 2,85-3,20 (3H, m), 3,50-4,00 (2H, m), 5,00-5,50 (1H, m), 6,80-8,10 (7H, m), 8,20 at 8.60 (2H, m), 10,50-11,20 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 320:

(1-Amino-cyclopropyl)-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)methanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method but using 1-amino-cyclopropanecarbonitrile acid.

1H NMR (CD3OD) δ: 0,80-1,10 (4H, m), 1,88-2,17 (3H, m), 2,32-to 2.40 (1H, m), of 3.12 (3H, s)4,06 (2H, users), to 5.21 (1H, users), 7,18-rate of 7.54 (5H, m), to $ 7.91-to 7.99 (3H, m), of 8.27 (1H, d, J=8.0 Hz), 8,73 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 518[M+H]

Example 321:

5-(6-(1-Acetyl-pyrrolidin-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile

Specified in the title compound obtained as an oily substance in the same manner as in example 121 (step 9)-(stage 12) and example 314, or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of 1-(2-(4,5-diamino-2-benzyloxy-phenyl)pyrrolidin-1-yl)ethanone obtained in example 309 (stage 1), and pyrazin-2-carboxaldehyde.

1H NMR (CDCl3) δ: 1,67-2,47 (7H, m), 3,60-to 3.92 (2H, m), 5,11-to 5.35 (1H, m), 7,00-to 7.77 (4H, m), of 8.47-8,73 (3H, m), 9,52-9,68 (1H, m), 10,88-11,94 (1H, m)

ESI-MS (m/e): 426[M+H]

Example 322:

1-(2-(2-(5-Cyano-pyridi the-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 307, or in accordance with the method or by combining with an ordinary method but using 5-cyano-pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,05-to 2.40 (7H, m), 2,80-3,20 (3H, m), 3,60-4,00 (2H, m), of 5.05-of 5.45 (1H, m), 6.90 to-7,80 (4H, m), 7,80-of 8.00 (2H, m), 8,05-to 8.20 (1H, m), 8,40 at 8.60 (1H, m), 8,80-9,00 (1H, m), the 10.40-10,80 (1H, m)

ESI-MS (m/e): 502[M+H]

Example 323:

1-(2-(2-(4-Chloro-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 307, or in accordance with the method or by combining with an ordinary method but using 4-chloro-pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,67-to 2.40 (7H, m), 3.00 and-3,13 (3H, m), 3,54-3,9 1 (2H, m), 5,10-5,44 (1H, m), 6,79-7,52 (5H, m), of 7.64-of 7.97 (2H, m), at 8.36-to 8.57 (2H, m), 10,75-11,24 (1H, m)

ESI-MS (m/e): 511[M+H]

Example 324:

1-(2-(2-(5-Ethoxy-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 307, or in accordance with the method or by combining with an ordinary method but using 5-ethoxy-pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 2,00 is 3.40(10H, m), 3,60-4,00 (3H, m), 4,20-5,20 (4H, m), 5,80-6,40 (1H, m), 7,20-9,20 (9H, m), 11,50-12,00 (1H, m)

ESI-MS (m/e): 521[M+H]

Example 325:

TRANS-1-(4-acetoxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of 1-(2-fluoro-4-nitro-phenyl)-3-butene-1-ol:

0,65 ml of titanium tetrachloride are added to a solution in chloroform (12 ml) of 2.00 g of 4-nitro-2-fluoro-benzaldehyde, obtained according to the method described in US 6239152, and the reaction liquid was stirred at room temperature for 10 minutes and then there was added 2.4 ml allyl-trimethyl-silane, and the reaction liquid was stirred at room temperature for 20 minutes. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=3/1), getting mentioned in the title compound in the form of a solid orange color.

(Stage 2) Obtaining N-(1-(2-fluoro-4-nitro-phenyl)-3-butenyl)ndimethylacetamide:

0,29 ml methanesulfonyl chloride and 0.63 ml of triethylamine are added to a solution in chloroform (10 ml) 480 mg of 1-(2-fluoro-4-nitro-phenyl)-3-butene-1-ol and the reaction liquid was stirred at room temperature for 15 minutes. Reacciona the liquid, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to give crude product as an oily material light yellow color. 310 mg of sodium azide are added to a solution in dimethylformamide (10 ml) of the crude product and the reaction liquid was stirred at 45°C for 30 minutes. The reaction liquid was diluted with ethyl acetate, washed with water and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product as an oily substance brown. 1.0 g of triphenylphosphine and 2 ml of water are added to a solution in tetrahydrofuran (10 ml) of the obtained crude product, and the reaction liquid is stirred for 12 hours with heating at boiling under reflux. 1N hydrochloric acid is added to the reaction liquid and the organic layer removed. The aqueous layer was alkalinized added aqueous 1N solution of sodium hydroxide. It is extracted with chloroform and dried with anhydrous sodium sulfate and the solvent is evaporated under reduced pressure, getting 380 mg of crude product as an oily substance brown. of 0.50 ml of triethylamine, 0.25 ml of acetic anhydride and 20 mg of 4-dimethylaminopyridine added to a solution in chloroform (10 ml) 380 mg of crude product, and the reaction liquid was stirred at room temperature for 30 minutes. The solvent is evaporated at igenom pressure and the residue purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting listed in the title compound as an oily substance brown.

(Stage 3) to Obtain 1-acetyl-2-(2-fluoro-4-nitro-phenyl)-4-hydroxy-pyrrolidine:

1 ml of water and 600 mg of iodine are added to a solution in tetrahydrofuran (4 ml) 200 mg N-(1-(2-fluoro-4-nitro-phenyl)-3-butenyl)ndimethylacetamide and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium bicarbonate, water and saturated sodium thiosulfate solution and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product. 0.25 ml of triethylamine, with 0.13 ml of acetic anhydride and 10 mg of 4-dimethylaminopyridine added to a solution in chloroform (5 ml) of the crude product and the reaction liquid was stirred at room temperature for 15 minutes. The solvent is evaporated under reduced pressure, 20 mg of potassium carbonate are added to a solution in methanol (5 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 15 minutes. The solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=30/1), getting mentioned in the title compound is a colourless solid diastereomeric mixture.

(Stage 4) to Obtain 1-acetyl-2-(2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine:

0.06 ml of acetic anhydride are added to a solution in pyridine (2 ml) 140 mg of 1-acetyl-2-(2-fluoro-4-nitro-phenyl)-4-hydroxy-pyrrolidine and the reaction liquid was stirred overnight at 50°C. the Solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: ethyl acetate)to give 150 mg of product. About 50 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in methanol (3 ml) 57 mg of the product and the reaction liquid is stirred in hydrogen atmosphere for 30 minutes. Then the catalyst is removed by filtration and the solvent is evaporated under reduced pressure. 30 mg of pyridine-2-carboxylic acid and 50 mg of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (2 ml) of the residue and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily yellow substance.

(Stage 5 Receiving TRANS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine and CIS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine:

0.1 ml of fuming nitric acid are added to a solution in triperoxonane acid (0.5 ml) 36 mg of 1-acetyl-2-(2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine and the reaction liquid was stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=15/1)to give 30 mg of a mixture of diastereoisomers specified in the connection header in the form of a solid white color. The resulting mixture of diastereomers clear distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to divide the mixture into individual diastereomers specified in the title compounds, each in the form of a solid yellow (Rf indicator: TRANS form>CIS form.)

(Stage 6) to Obtain TRANS-1-(4-acetoxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-pyrrolidin-1-yl)alanon:

10 mg 4-methanesulfonyl-phenol and 20 mg of cesium carbonate are added to a solution in dimethylformamide (0.5 ml) 21 mg of TRANS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine and the reaction liquid was stirred at 90°C for 1 hour. Add 100 mg of the dihydrate of tin chloride (II) and the reaction liquid was stirred at 90°C for 5 hours is. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily yellow substance.

1H NMR (CD3OD) δ: 1,50-1,90 (3H, m), 2,10-of 2.53 (2H, m), 2,98 (3H, s), 3,60-are 3.90 (2H, m), 5,13-of 5.26 (2H, m), 7.03 is-the 7.65 (5H, m), 7,78-7,87 (3H, m), 8,10-8,18 (1H, m), 8,59 (1H, s)

ESI-MS (m/e): 535[M+H]

Example 326:

TRANS-1-(4-hydroxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

of 0.015 ml of 25% sodium methoxide are added to a solution in methanol (2 ml) 40 mg of TRANS-1-(4-acetoxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 325, and the reaction liquid was stirred at room temperature for 10 minutes. The solvent is evaporated under reduced pressure and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining specified in the title compound in the form of terdag the substance of white color.

1H NMR (CD3OD) δ: 1,48 is 2.80 (5H, m), 2,99-3,10 (3H, m), 3,48-4,10 (2H, m), 4,40-4,60 (1H, m), 5.25-in of 5.50 (1H, m), 7,00-to 7.50 (5H, m), 7,75-of 8.00 (3H, m), 8,24-8,48 (1H, m), 8,48-to 8.70 (1H, m), 10,70-11,20 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 327:

CIS-1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

0,02 ml trichloride bis(2-methoxyethyl)minculete added to a solution in chloroform (1 ml) 10 mg of TRANS-1-(4-hydroxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 326, and the reaction liquid was stirred at room temperature for 10 minutes. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound in the form of a solid white color.

1H NMR (CD3OD) δ: 1,92 (3Hx1/2, p), 2,22 (3Hx1/2, p), 2,22 is 2.80 (2H, m), 3,13 (3H×1/2, (C)and 3.15 (3H×1/2, s), 3,80-and 4.40 (2H, m), 5,20-of 5.50 (2H, m), 7,20-7,80 (5H, m), of 7.90-8,10 (3H, m), of 8.28 (1H, t, J=7.8 Hz), a total of 8.74 (1H, users)

ESI-MS (m/e): 495[M+H]

Example 328:

CIS-1-(4-acetoxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a colorless solid in the same manner as in example 325 (stage 6), or in accordance with the method, or what EDINENIE with in the usual way, but using CIS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine obtained in example 325 (stage 5).

1H NMR (CD3OD) δ: 1,40-1,90 (3H, m), 2,20-to 2.55 (2H, m)of 3.00 (3H, s), 3,62-are 3.90 (2H, m), 5,12 is 5.28 (2H, m), 6,98 to 7.75 (5H, m), 7,78-7,88 (3H, m), 8,11-8,19 (1H, m), at 8.60 (1H, s)

ESI-MS (m/e): 535[M+H]

Example 329:

CIS-1-(4-hydroxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a colorless solid in the same manner as in example 326, or in accordance with the method or by combining with an ordinary method but using CIS-1-(4-acetoxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 328.

1H NMR (CD3OD) δ: 1,80-2,00 (3H, m), 2,04 is 2.75 (2H, m), 3,12-and 3.16 (3H, m), 3,40-4,00 (2H, m), 4,45-4,55 (1H, m), 5.25 to 5,43 (1H, m), 7.18 in-7,42 (3H, m), 7,50-to 7.59 (1H, m), 7,62-to 7.77 (1H, m), of 7.90-8,08 (3H, m), 8,24-8,32 (1H, m), 8,75-8,81 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 330:

TRANS-1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as solid light yellow color in the same way as in example 327, or in accordance with the method or by combining with an ordinary method but using CIS-1-(4-hydroxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-the l-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone.

1H NMR (CD3OD) δ: 1,70-by 2.73 (5H, m), 3,11-3,37 (3H, m), 3,62-4,5 l (2H, m), 5,24-of 5.45 (2H, m), 7,13-7,76 (5H, m), 7,94-of 8.00 (3H, m), 8,28-of 8.33 (1H, m), 8,73-8,79 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 331:

1-(4-Oxo-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

0.003 ml of dimethyl sulfoxide are added to a solution in chloroform (1 ml) 0.003 ml of oxalicacid at -50°C and the reaction liquid was stirred at the same temperature for 5 minutes. The solution in chloroform (1 ml) of 6.7 mg of TRANS-1-(4-hydroxy-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 326, add to the reaction liquid and the reaction liquid was stirred at -50°C for 15 minutes. Add 0,02 ml of triethylamine and the reaction liquid was stirred at room temperature for 5 minutes and the reaction liquid was diluted with ethyl acetate, washed with aqueous saturated solution of ammonium chloride and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous solution of hydrocar is onata sodium and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

1H NMR (CD3OD) δ: 2,03 (3H, s), 2,68 (2H, s), and 3.16 (3H, s), 4.09 to 4,22 (2H, m), 5,70 is 5.77 (1H, m), 7,05-7,80 (5H, m), 7,94-8,0l (3H, m), 8,24-8,32 (1H, m), 8,72-8,77 (1H, m)

ESI-MS (m/e): 491[M+H]

Example 332:

1-(4,4-Debtor-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of 1-acetyl-2-(2-fluoro-4-nitro-phenyl)-4,4-debtor-pyrrolidine:

a 0.035 ml of dimethyl sulfoxide are added to a solution in chloroform (3 ml) a 0.035 ml oxalicacid at -50°C and the reaction liquid was stirred at the same temperature for 5 minutes. The solution in chloroform (2 ml) 40 mg of 1-acetyl-2-(2-fluoro-4-nitro-phenyl)-4-hydroxy-pyrrolidine obtained in example 325 (stage 3), is added to the reaction liquid and the reaction liquid was stirred at -50°C for 10 minutes. Add 0.10 ml of triethylamine and the reaction liquid was stirred at room temperature for 5 minutes, then the reaction liquid was diluted with ethyl acetate, washed with aqueous saturated solution of ammonium chloride and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and added 0.06 ml of trichloride bis(2-methoxyethyl)aminomethane to a solution in chloroform (1 ml)of the obtained residue, and the reaction liquid was stirred overnight at 70° C. the Solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1)to give specified in the header of the connection.

(Stage 2) Obtaining 1-(4,4-debtor-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

Specified in the title compound obtained as a solid substance of white color in the same way as in example 325 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 1-acetyl-2-(2-fluoro-4-nitro-phenyl)-4,4-debtor-pyrrolidine obtained (stage 1).

1H NMR (CD3OD) δ: 2,03 (3Hx1/2, C)2,05 (3Hx1/2, p), 2,50-2,63 (1H, m), 2,85 is 3.15 (1H, m), 3,14 (3Hx1/2, (C)and 3.15 (3Hx1/2, s), 3.95 to of 4.25 (2H, m), 5,44-to 5.58 (1H, m), 7,22-7,29 (2H, m), 7,26-7,42 (1H, m), of 7.48-7,54 (1H, m), to 7.61-to 7.68 (1H, m), 7,94-of 8.04 (3H, m), compared to 8.26-8,32 (1H, m), 8,72-8,77 (1H, m)

ESI-MS (m/e): 513[M+H]

Example 333:

CIS-1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer A and enantiomer B

45 mg of racemic CIS-1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 327, share with columns for the separation of optical isomers (CHIRALPAK AD-H 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/2-propanol=30/70, flow rate: 10 ml/min), enantiomer is A (retention time: 18 min) and enantiomer B (retention time: 22 min), each in the form of a solid white color.

Enantiomer A

ESI-MS(m/e): 495 [M+H]

Enantiomer B

ESI-MS(m/e): 495 [M+H]

Example 334:

Methyl 6-(6-(1-acetyl-pyrrolidin-2-yl)-5-(4-methanesulfonyl-phenoxy)-1H-benzimidazole-2-yl)nicotinate

Specified in the header of the connection get in a solid yellow color in the same manner as in example 307, or in accordance with the method or by combining with an ordinary method but using 5-methyl ether complex pyridine-2,5-dicarboxylic acid.

1H NMR (CDCl3) δ: 1,20-to 2.40 (7H, m), 2,80-3,20 (3H, m), 3,40-4,00 (2H, m)to 3.99 (3H, s), of 5.05-of 5.45 (1H, m), 6,80-7,80 (4H, m), 7,80-with 8.05 (2H, m), 8,35 at 8.60 (2H, m), 9,10-of 9.30 (1H, m), or 10.60-11,30 (1H, m)

ESI-MS (m/e): 535[M+H]

Example 335:

6-(6-(1-Acetyl-pyrrolidin-2-yl)-5-(4-methanesulfonyl-phenoxy)-1H-benzimidazole-2-yl)nicotinic acid

Specified in the title compound obtained as solid light yellow color in the same manner as in example 121 (step 6), or in accordance with the method or by combining with an ordinary method, but using methyl 6-(6-(1-acetyl-pyrrolidin-2-yl)-5-(4-methanesulfonyl-phenoxy)-1H-benzimidazole-2-yl)nicotinate obtained in example 334.

1H NMR (DMSO-d6) δ: 1,60-2,60 (7H, m), 3,21 (3H, s), 3,60-4,00 (2H, m), 5,00-5,20 (1H, m), 6.90 to-7,60 (4H, m), 7,80-of 8.00 (2H, m), 8,30 at 8.60 (2H, m), 9,20 (1H, s)

ESI-MS (m/e): 521[M+H]

Example 336:

Dimethylamide 2-(6-(4-methanesulfonyl-phenoxy)-2-Piri is in-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxylic acid

(Stage 1) preparation of 4-nitrophenyl 2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-2,3-dihydro-1H-benzimidazole-5-yl)pyrrolidin-1-carboxylate:

to 0.060 ml of triethylamine and 21 mg of 4-nitrobenzylamine add accordingly to the solution in tetrahydrofuran (1 ml), 37 mg of enantiomer B 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 163, and the reaction liquid was stirred overnight at room temperature. The reaction solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

(Stage 2) Receive dimethylamide 2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxylic acid:

1 ml of dimethylamine (2.0 M solution in tetrahydrofuran) are added to a solution in tetrahydrofuran (1 ml), 20 mg of 4-nitrophenyl 2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-2,3-dihydro-1H-benzimidazole-5-yl)pyrrolidin-1-carboxylate and the reaction liquid was stirred overnight in a sealed tube at 100°C. the reaction Solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average giving the situation [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

1H NMR (CD3OD) δ: 1,80-of 1.92 (2H, m), 1,94-2,07 (1H, m), 2,33-to 2.42 (1H, m), 2,80 and 2,85 (total 6H, each users), of 3.12 (3H, s), 3,52-to 3.58 (1H, m), 3,62-of 3.78 (1H, m), 5,19-of 5.26 (1H, m), 7,16-7,80 (5H, m), to $ 7.91-to 7.99 (3H, m), of 8.27 (1H, d, J=7,6 Hz), 8,73 (1H, users)

ESI-MS (m/e): 506[M+H]

Example 337:

1-(2-(2-(6-Hydroxy-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection get in a solid yellow color in the same manner as in example 307, or in accordance with the method or by combining with an ordinary method but using 6-hydroxy-pyridine-2-carboxylic acid.

1H NMR (CD3OD) δ: 1,75-2,47 (7H, m), 2,97-3,26 (4H, m), 3,44-of 3.96 (2H, m), 5,20-of 5.40 (1H, m), 6,60-8,05 (10H, m)

ESI-MS (m/e): 493[M+H]

Example 338:

1-(2-(6-(4-Fluoro-phenylsulfanyl)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

(Stage 1) preparation of tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrol-1-carboxylate:

1.6 g of 1-(tert-butoxycarbonyl)pyrrol-2-Bronevoy acid, 200 mg tetranitroaniline palladium, 5 m of the water saturated solution of sodium carbonate and 5 ml of water is added appropriately to the solution of dimethoxyethane (10 ml) and 1 g of 4-bromo-3-fluoro-phenylamine and the reaction liquid is stirred in a nitrogen atmosphere at 70° C for 3 hours. After cooling, the reaction liquid is filtered through Celite and the filtrate diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=2/1)to give specified in the title compound in the form of solid light brown color.

(Stage 2) Obtain tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrolidin-1-carboxylate:

5 ml of water and 660 mg of catalyst 5% PT on coal are added to a solution in 2-propanol (50 ml) 2.2 g of tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrol-1-carboxylate and stirred in a hydrogen atmosphere under a pressure of 50 kgf/cm2at 50°C for 1 day. The catalyst was removed by filtration through Celite, the solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1), getting mentioned in the title compound as an oily substance brown.

(Stage 3) Getting (4-(1-acetyl-pyrrolidin-2-yl)-3-fluoro-phenyl)amide pyridine-2-carboxylic acid:

90 mg of pyridine-2-carboxylic acid and 190 mg of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide add auth to a solution in pyridine (2 ml) 181 mg of tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrolidin-1-carboxylate and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and 2 ml of 4n. hydrochloric acid solution in dioxane are added to 300 mg of the obtained residue, and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with chloroform and alkalinized added aqueous saturated solution of sodium bicarbonate, the organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and 0,020 ml of acetic anhydride are added to a solution in pyridine (1 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 20 minutes. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 4) Getting (4-(1-acetyl-pyrrolidin-2-yl)-5-fluoro-2-nitro-phenyl)-amide feast is DIN-2-carboxylic acid:

94 mg of potassium nitrate are added to a solution in triperoxonane acid (3 ml) of (4-(1-acetyl-pyrrolidin-2-yl)-3-fluoro-phenyl)amide pyridine-2-carboxylic acid and the reaction liquid was stirred at room temperature for 2 days. The reaction liquid is distilled under reduced pressure, diluted with chloroform and alkalinized water saturated solution of sodium bicarbonate and then extracted with chloroform. The organic layers are combined, washed with a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting mentioned in the title compound in the form of a solid of light yellow color.

(Stage 5) to Obtain 1-(2-(6-(4-fluoro-phenylsulfanyl)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

20 mg of 4-fluoro-bentolila and 30 mg of potassium carbonate are added to a solution in N,N-dimethylformamide (1 ml) 50 mg (4-(1-acetyl-pyrrolidin-2-yl)-5-fluoro-2-nitro-phenyl)amide pyridine-2-carboxylic acid and the reaction liquid was stirred at 100°C for 2 hours. 30 mg of the dihydrate of tin chloride (II) is added to the reaction liquid and the reaction liquid was stirred at 100°C for 3 hours. After cooling to implement the operating fluid is diluted with saturated aqueous sodium hydrogen carbonate and extracted with chloroform, the organic layer was dried with magnesium sulfate and the solvent is evaporated under reduced pressure. The resulting residue is purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 3,60-4,00 (2H, m), 5,20-5,80 (1H, m), 6.90 to-7,10 (2H, m), 7,15-7,80 (5H, m), 7,80-8,00 (1H, m), 8,30-to 8.45 (1H, m), 8,55-to 8.70 (1H, m), or 10.60-11,20 (1H, m)

ESI-MS (m/e): 433[M+H]

Example 339:

1-(2-(6-(4-methanesulfonyl-phenylsulfanyl)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-methanesulfonyl-bentolila.

1H NMR (CDCl3) δ: 1,40-of 2.45 (7H, m), 2,80-3,20 (3H, m), 3,50-4,00 (2H, m), 5,20-the 5.65 (1H, m), 7,10-of 8.25 (8H, m), 8,30-and 8.50 (1H, m), 8,50-8,80 (1H, m), or 10.60-11,40 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 340:

N-(5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-yl)ndimethylacetamide

(Stage 1) preparation of 1-(2-(6-(6-amino-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

of 53.5 mg 5-bromo-2-nitro-pyridine, 84,2 mg of cesium carbonate and 25 mg of copper oxide (II) are added to a solution of pyridine (1 ml) 55,0 mg of 1-(2-(6-hydro is si-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone, obtained in example 121 (step 10), and the reaction liquid was stirred overnight in a sealed tube at 120°C. After cooling, aqueous saturated solution of ammonium chloride and a saturated solution of salt add accordingly to the reaction liquid, extracted it with ethyl acetate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and 0,016 ml of hydrazine monohydrate and 20 mg of the catalyst of Raney Nickel with a developed surface are added to a solution in ethanol (2 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 30 minutes. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure. The resulting residue is purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound as an oily yellow substance.

(Stage 2) Obtaining N-(5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-yl)ndimethylacetamide:

0,005 ml of acetic anhydride are added to a solution in pyridine (1 ml) of 13.7 mg of 1-(2-(6-(6-amino-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid viparis the Ute under reduced pressure, the resulting residue is dissolved in 1 ml triperoxonane acid and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid is distilled under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid] and column chromatography on silica gel (manifesting solvent: chloroform/methanol=9/1), getting mentioned in the title compound as an oily substance.

1H NMR (CDCl3) δ: 1,64-2,44 (10H, m), 3,57-3,91 (2H, m), 5,26-5,62 (1H, m), 6,76-a total of 8.74 (10H, m), 10,59-to 11.31 (1H, m)

ESI-MS (m/e): 457[M+H]

Example 341:

1-(2-(6-(6-Acetyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as an oily substance in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 1-(5-bromo-pyridine-2-yl)ethanone.

1H NMR (CDCl3) δ: 1,66-2,42 (7H, m), 2,59-to 2.74 (3H, m), 3,51-are 3.90 (2H, m), 5,12-of 5.45 (1H, m), 6,85-8,10 (6H, m), 8,30-to 8.70 (3H, m), 10,86-11,24 (1H, m)

ESI-MS (m/e): 442[M+H]

Example 342:

2-(5-Bromo-pyridine-2-yl)-5-(4-methanesulfonyl-phenoxy)-6-pyrrolidin-2-yl-1H-benzimidazole, enantiomer A and enantiomer B

100 mg of racemic 2-(5-bromo-pyridine-2-yl)-5-(4-methanesulfonyl-phenoxy)-6-Pirro is one-2-yl-1H-benzimidazole, obtained in example 306, share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/isopropanol/diethylamine=20/80/0,1, flow rate: 10 ml/min), the enantiomer A (retention time: 24 min) and enantiomer B (retention time: 27 minutes) each in the form of an oily substance.

Example 343:

1-(2-(2-(5-Bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer A

0,020 ml of acetic anhydride are added to a solution in pyridine (1 ml) 43 mg of enantiomer A of 2-(5-bromo-pyridine-2-yl)-5-(4-methanesulfonyl-phenoxy)-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 342, and the reaction liquid was stirred at room temperature for 10 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, and extracted it with chloroform, the organic layer was dried with magnesium sulfate and the solvent is evaporated under reduced pressure. The resulting residue is purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,60-to 2.40 (7H, m), 2,80-3,20 (3H, m), 3,50-of 3.95 (2H, m), of 5.05-of 5.45 (1H, m), 6.90 to-7,80 (5H, m), 7,80-of 8.00 (2H, m), 8,10-8,30 (1H, m), 8,60-8,80 (1H, m)

ESI-MS (m/e): 555, 557[M+H]

Example 344:

-(2-(2-(5-Bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer B

Specified in the title compound obtained as a solid substance of white color in the same way as in example 343, or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of 2-(5-bromo-pyridine-2-yl)-5-(4-methanesulfonyl-phenoxy)-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 342.

Example 345:

1-(2-(6-(4-Methanesulfonyl-phenoxy)-2-(5-vinyl-pyridin-2-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection get in a solid yellow color in the same manner as in example 307, or in accordance with the method or by combining with an ordinary method but using 5-vinyl-pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,20-to 2.40 (7H, m), 2,90 is 3.15 (3H, m), 3,50-are 3.90 (2H, m), 5,00-of 5.45 (1H, m), of 5.48 (1H, DD, J=5,6, 11.2 Hz), 5,94 (1H, DD, J=5,6, and 17.6 Hz), 6,70-6,85 (1H, m), 7,00-of 7.25 (2H, m), 7,25-7,80 (2H, m), 7,80-8,00 (3H, m), 8,30-to 8.40 (1H, m), 8,55-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 503[M+H]

Example 346:

1-(2-(6-(6-(1-Hydroxy-1-methyl-ethyl) - pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

0.1 ml metallyte (a 1.0 M solution in diethyl simple ether) is added at -78°C to a solution in tetrahydrofuran (1.5 ml) of 15.0 mg of 1-(2-(6-(6-acetyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in the example 341, and the reaction liquid was stirred at-78° C for 30 minutes. The reaction liquid was poured into aqueous saturated solution of ammonium chloride, extracted with chloroform and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=7,5/1), getting mentioned in the title compound in the form of a solid yellow color.

1H NMR (CDCl3) δ: 1,46-to 1.63 (6H, m), 1,63-2,47 (7H, m), 2,87-2.99 and 3,34-3,91 (total 3H, each m), 5,18-the 5.51 (1H, m), 6,72-to $ 7.91 (6H, m), 8.17-a 8,68 (3H, m), 10,54-10,94 (1H, user.)

ESI-MS (m/e): 458[M+H]

Example 347:

Ethyl(5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-yl)carbamate

0.003 ml ethyl-chloroformate added to a solution in pyridine (1 ml) of 14.4 mg of 1-(2-(6-(6-amino-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 340 (stage 1), and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid is distilled under reduced pressure and the resulting residue is dissolved in 1 ml triperoxonane acid and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid is distilled under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid] and column chromatography on silica gel (manifesting solvent: chloroform/methanol=9/1), getting mentioned in the title compound as an oily yellow substance.

1H NMR (CDCl3) δ: 1,14-is 1.51 (3H, m), 1,52-2,46 (7H, m), 2,78-2,93 and 3,51-3,88 (total 3H, each m), 4,16-4.26 deaths (2H, m), 5,27-5,63 (1H, m), 6,80-8,69 (10H, m)

ESI-MS (m/e): 487[M+H]

Example 348:

1-(2-(6-(6-(5-Methyl-[1,2,4]oxadiazol-3-yl)pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 153, or in accordance with the method or by combining with an ordinary method but using 5-bromo-2-cyano-pyridine.

1H NMR (CDCl3) δ: 1,49-2,42 (7H, m), 2,54-a 2.71 (3H, m), 3,50-3,88 (2H, m), 5,04-of 5.48 (1H, m), 7,00-8,67 (10H, m)

ESI-MS (m/e): 482 [M+H]

Example 349:

3-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-3-oxo-propionitrile

Specified in the title compound obtained as a solid substance of white color in the same way as in example 296, or in accordance with the method or by combining with an ordinary method but using tsianuksusnogo acid.

1H NMR (CDCl3) δ: 1,80-of 2.05 (4H, m), 3,05-of 3.25 (4H, m), 3,47-3,93 (3H, m), 5,19-5,41 (1H, m), 7,00-to 7.59 (5H, m), 7,82-to 7.99 (3H, m), 8,35-to 8.41 (1H, m), 8,62-8,68 (1H,m)

ESI-MS (m/e): 502[M+H]

Example 350:

Cyclopropyl-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-methanon

Specified in the title compound obtained as a solid substance of white color in the same way as in example 296, or in accordance with the method or by combining with an ordinary method but using cyclopropanecarbonyl acid.

1H NMR (CDCl3) δ: 0,92-1,08 (4H, m), 1.60-to of 1.66 (2H, m), 1.85 to 1,99 (2H, m), 2,20-of 2.38 (1H, m), 3,05-is 3.08 (3H, m), 3,63-4,00 (2H, m), 5,33-5,41 (1H, m), 7,12-7,44 (5H, m), 7,86-a 7.92 (3H, m), 8,40-8,44 (1H, m), 8,60-8,68 (1H, m)

ESI-MS (m/e): 503[M+H]

Example 351:

3,3,3-Cryptor-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)propane-1-he

Specified in the title compound obtained as a solid substance of white color in the same way as in example 296, or in accordance with the method or by combining with an ordinary method but using 3,3,3-Cryptor-propionic acid.

1H NMR (CDCl3) δ: 1,85-to 2.40 (4H, m), 2,90-3,27 (5H, m), 3,65-are 3.90 (2H, m), 5,15-5,43 (1H, m), 6,97-7,63 (5H, m), 7,84-of 7.96 (3H, m), scored 8.38-8,43 (1H, m), 8,60-8,68 (1H, m)

ESI-MS (m/e): 545[M+H]

Example 352:

(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-(tetrahydrofuran-2-yl)-methanon

Specified in the title compound obtained as a solid substance of white color in the same way as in example 296, or is relevant to the AI by the way, or Association with an ordinary method, but using tetrahydrofuran-2-carboxylic acid.

1H NMR (CDCl3) δ: 1,85 is 2.33 (7H, m), 3,05-3,10 (3H, m), 3,63-4,08 (5H, m), 4,15-to 4.62 (1H, m), 5,33-5,62 (1H, m), 7,11-of 7.55 (5H, m), 7,84-of 7.95 (3H, m), of 8.37-8,42 (1H, m), 8,60-8,67 (1H, m)

ESI-MS (m/e): 533[M+H]

Example 353:

N-(2-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)ndimethylacetamide

Specified in the title compound obtained as a solid substance of white color in the same way as in example 296, or in accordance with the method or by combining with an ordinary method but using acetylamino-acetic acid.

1H NMR (CDCl3) δ: 1,90-of 2.05 (8H, m), 3,07-to 3.09 (3H, m), 3,47-4,01 (3H, m), 5,16-of 5.40 (1H, m), 6,52-6,70 (1H, m),? 7.04 baby mortality-7,20 (2H, m), 7,33-EUR 7.57 (2H, m), 7,84-7,98 (3H, m), 8,35 is 8.38 (1H, m), 8,61-8,67 (1H, m)

ESI-MS (m/e): 534[M+H]

Examples 354 (diastereoisomer A), 355 (diastereoisomer B):

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)ethanol, diastereoisomer A, and the diastereoisomer B

Specified in the title compound obtained as a solid mixture of light-yellow color of the diastereomers in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, 1-pyrrolidin-2-yl-ethanol. The mixture of diastereomers of cleansing the t distribution thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1) to separate the diastereomers A and B, each in the form of a solid of light yellow color.

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)ethanol, diastereoisomer A

1H NMR (CD3OD) δ: of 1.09 (3H, d, J=6,7 Hz), 1,66-of 1.78 (1H, m), 1,80-1,99 (3H, m), 3,06-3,18 (1H, m), of 3.12 (3H, s), 3,61 at 3.69 (1H, m), 3,78-a 3.83 (1H, m), 3,90-to 3.99 (1H, m), 6,97-7,8l (5H, m), 7,89-of 8.00 (3H, m), compared to 8.26 (1H, d, J=8,2 Hz), a total of 8.74 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 479[M+H]

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)ethanol, diastereoisomer B

1H NMR (CD3OD) δ: 0,76 (3H, d, J=6.3 Hz), 1.70 to to 1.82 (3H, m), 1,92 is 2.00 (1H, m), 3,06-3,13 (1H, m), 3,10 (3H, s), 3,61 at 3.69 (1H, m), 3,83-are 3.90 (1H, m), 3.95 to a 4.03 (1H, m),? 7.04 baby mortality (2H, d, J=8,9 Hz), 7,37-7,44 (2H, m), 7,46-7,49 (1H, m), 7,89 (2H, d, J=8,9 Hz), 7,93-to 7.99 (1H, m), of 8.27 (1H, d, J=7.8 Hz), a total of 8.74 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 479[M+H]

Example 356:

5-(2-(1-Fluoro-ethyl)-pyrrolidin-1-yl)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

0,007 ml of the TRIFLUORIDE diethylaminoethyl added at -78°C to a solution in chloroform (1 ml) 21 mg of diastereoisomer A 1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)ethanol obtained in example 354, and the reaction liquid was stirred at -78°C for 1 hour. The reaction liquid is heated to room temperature and aqueous saturated sodium hydrogen carbonate solution is added to the reaction liquid and the ZAT is extracted with its ethyl acetate and dried with anhydrous magnesium sulfate. The solvent is evaporated and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: and 1,18 1,24 (total 3H, each d, J=6,3, 6,7 Hz), 1,53-of 1.78 (1H, m), 1,83 is 2.00 (3H, m), 3,11 (3H, s), 3,11-3,20 (1H, m), 3,52-3,61 (1H, m), 3,89-4,01 (1H, m), 4.63 to-to 4.87 (1H, m),? 7.04 baby mortality (2H, d, J=9.0 Hz), 7,21-7,53 (3H, m), 7,89 (2H, d, J=9.0 Hz), of 7.96-8,02 (1H, m), of 8.27 (1H, d, J=7.8 Hz), a total of 8.74 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 481[M+H]

Example 357:

5-(2-(1-Fluoro-ethyl)pyrrolidin-1-yl)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 356, or in accordance with the method or by combining with an ordinary method but using diastereoisomer B 1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)-ethanol obtained in example 355.

1H NMR (CD3OD) δ: of 0.99 and 1.09 (total 3H, each d, J=6,5, 6.2 Hz), 1,59 of-1.83 (3H, m), 1.93 and-2,03 (1H, m), 3.00 and-3,10 (1H, m)to 3.09 (3H, s), 3,54-to 3.67 (1H, m), 4,10-4,19 (1H, m), 4,37-of 4.54 (1H, m),? 7.04 baby mortality (2H, d, J=8,9 Hz), of 7.36-of 7.48 (3H, m), 7,86 (2H, d, J=8,9 Hz), 7,94-7,98 (1H, m), of 8.25 (1H, d, J=7.8 Hz), 8,72 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 481[M+H]

Example 358:

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon

0,080 ml oxacillin the and and 0.087 ml of dimethyl sulfoxide is added to 3 ml of methylene chloride at -78° C and the reaction liquid was stirred at -78°C for 10 minutes and then added to a solution in methylene chloride (2 ml) 146 mg of the mixture of diastereomers of 1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)-ethanol obtained in examples 354 and 355, at -78°C. the Reaction liquid was stirred at -78°C for 30 minutes and add to it at 0.42 ml of triethylamine and the reaction mixture stirred at -78°C for 10 minutes, then warmed to room temperature. Aqueous saturated solution of ammonium chloride is added to the reaction liquid, extracted it with ethyl acetate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: 1,78-2,07 (3H, m), of 1.94 (3H, s), 2,20-to 2.29 (1H, m), 3,06 (3H, s), 3,37 is-3.45 (1H, m), 3,64-of 3.77 (1H, m), 4,27-4,30 (1H, m), 6,80-7,44 (5H, m), 7,80-7,88 (3H, m), 8,27-to 8.40 (1H, m), 8,61-to 8.62 (1H, m,)

ESI-MS (m/e): 477[M+H]

Examples 359 (enantiomer A), 360 (enantiomer B):

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon, enantiomer A and enantiomer B

27 mg of racemic 1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)p is Raiden-2-yl)ethanone, obtained in example 358, share with columns for the separation of optical isomers (CHIRALPAK AD-H 2 cmϕ×25 L (Daicel Chemical), mobile phase: ethanol, flow rate: 10 ml/min), the enantiomer A (retention time: 20,8 min) and enantiomer B (retention time: 46,9 min), each in the form of a solid of light yellow color.

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon, enantiomer A

ESI-MS(m/e): 477 [M+H]

1-(1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon, enantiomer B

ESI-MS(m/e): 477 [M+H]

Example 361:

1-(1-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color as in the examples 354, 355 and 358, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 196 (step 3), and 1-methyl-1-(2-pyrrolidinyl)ethanol.

1H NMR (CD3OD) δ: 1,80-2,10 (3H, m), of 2.08 (3H, s), 2,28-2,39 (1H, m), 3,24 (3H, s), 3,40-3,47 (1H, m), 3,66-to 3.73 (1H, m), 4,46 (1H, t, J=7.4 Hz), 7,17 (1H, s), 7,40 (1H, s)of 7.48 (1H, DD, J=2.7, and an 8.8 Hz), 7,54 (1H, DD, J=4,9, a 7.6 Hz), 8,02 (1H, dt, J=0,8, 7,8 Hz), 8,07 (1H, DD, J=0,6, 8,8 Hz), 8,24 (1H, d, J=7.8 Hz), 8,46 (1H, DD, J=0,6, 2.7 Hz), 7,78 (1H, dt, J=0,8, a 4.9 Hz)

ESI-MS (m/e): 478 [M+H]

Examples 362 (enantio the EP A), 363 (enantiomer B):

1-(1-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon, enantiomer A and enantiomer B

34 mg of racemic 1-(1-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon obtained in example 361, share with columns for the separation of optical isomers (CHIRALPAK AD-H 2 cmϕ×25 L (Daicel Chemical), mobile phase: ethanol, flow rate: 10 ml/min), enantiomer A (retention time: 28,8 min) and enantiomer B (retention time: 48,2 min), each in the form of a solid of light yellow color.

1-(1-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon, enantiomer A

ESI-MS(m/e): 478 [M+H]

1-(1-(6-(6-Methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon, enantiomer B

ESI-MS(m/e): 478 [M+H]

Example 364:

(2S)-1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide

Specified in the title compound obtained as solid light yellow color in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and the hydrochloride of L-prolinamide.

1H NMR (CDCl3) δ: 1,91-2,03 (3H, m), 2.26 and-2,0 (1H, m)to 3.02 and 3.06 (total 3H, each s), 3,18 of 3.28 (1H, m), 3,63-3,91 (1H, m), 4,19-to 4.23 (1H, m), 6,04-6,13 (1H, m), 6,86-7,28 (4H, m), 7,37-7,41 (1H, m), of 7.48-rate of 7.54 (1H, m), 7,80-a 7.92 (3H, m), 8.34 per is 8.38 (1H, m), 8,48-8,63 (1H m)

ESI-MS (m/e): 478[M+H]

Example 365:

(2R)-1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide

Specified in the title compound obtained as solid light yellow color in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and D-prolinamide.

1H NMR (CDCl3) δ: 1,91-2,03 (3H, m), 2.26 and costs 2.50 (1H, m), to 3.02 and 3.06 (total 3H, each s), 3,18 of 3.28 (1H, m), 3,63-3,91 (1H, m), 4,19-to 4.23 (1H, m), 6,04-6,13 (1H, m), 6,86-7,28 (4H, m), 7,37-7,41 (1H, m), of 7.48-rate of 7.54 (1H, m), 7,80-a 7.92 (3H, m), 8.34 per is 8.38 (1H, m), 8,48-8,63 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 366:

6-((3R)-3-fluoro-pyrrolidin-1-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and (R)-3-terpinolene.

1H NMR (CD3OD) δ: 1,95-to 2.40 (2H, m), 3,10 (3H, s), 3.25 to to 3.73 (4H, m), 5,14-of 5.40 (1H, m), 7,06 (2H, d, J=8,9 Hz), 7,07-7,20 (1H, m), 7,32-7,40 1H, m), 7,42-of 7.48 (1H, m), 7,89 (2H, d, J=8,9 Hz), 7,93-to 7.99 (1H, m), 8,23 (1H, d, J=8,2 Hz), 8,71 (1H, d, J=5,1 Hz)

ESI-MS (m/e): 453[M+H]

Example 367:

1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-3-carboxamide

Specified in the header of the connection will receive the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and pyrrolidin-3-carboxamide.

1H NMR (CDCl3) δ: 2,03-of 2.30 (2H, m), 2,89-2,99 (1H, m), 3,06 (3H, s), 3,24-of 3.60 (4H, m), 5,70 and 5.86 (2H, m), 7,00-of 7.48 (5H, m), 7,80-of 7.90 (3H, m), 8.34 per-of 8.40 (1H, m), 8,57-8,64 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 368:

Methoxy-methyl-amide and (2R)-1-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxylic acid

Specified in the header of the connection will receive the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in example 14, and (R)-N-methoxy-N-methylpropanamide.

1H NMR (CD3OD) δ: 1,83-2,05 (3H, m), 2,25-to 2.40 (1H, m)to 3.09 (3H, users), of 3.13 (3H, s), 3,40-3,47 (1H, m), 3,68-of 3.78 (1H, m), of 3.84 (3H, users), 4,90-5,09 (1H, m), 7,06-7,30 (4H, m), 7,42-7,50 (1H, m), 7,87-of 8.00 (3H, m), 8,19-of 8.28 (1H, m), 8,70-8,76 (1H, m)

ESI-MS (m/e): 522[M+H]

Example 369:

(2R)-1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzoni the azole-5-yl)pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color as in the examples 354, 355 and 358, or in accordance with the method or by combining with an ordinary method but using 4-(6-econsultancy-pyridine-3-yloxy)-5-fluoro-2-nitro-phenylamine obtained in example 221 (step 2), and 1-(R)pyrrolidin-2-yl-ethanol.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 1,78-2,03 (3H, m), 2,03 (3H, s), 2,22 to 2.35 (1H, m), 3,30-of 3.43 (1H, m), 3,39 (2H, square, J=7,4 Hz), 3,64 of 3.75 (1H, m), 4,35 was 4.42 (1H, m), 7.03 is-of 7.48 (4H, m), of 7.90-to 7.99 (1H, m), 8,03 (1H, d, J=8.6 Hz), 8.17-a of 8.28 (1H, m), 8,43-8,46 (1H, m), 8,70 is 8.75 (1H, m)

ESI-MS (m/e): 492[M+H]

Example 370:

(2R)-1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color as in the examples 205 and 358, or in accordance with the method or by combining with an ordinary method but using 4-(6-econsultancy-pyridine-3-yloxy)-5-fluoro-2-nitro-phenylamine obtained in example 225 (stage 2), and 1-(R)pyrrolidin-2-yl-ethanol.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 1,80-2,03 (3H, m), 2,04 (3H, s), 2,24-of 2.34 (1H, m), 3,30 is-3.45 (1H, m), 3,39 (2H, square, J=7,4 Hz), 3,63-3,74 (1H, m), 4,37-of 4.44 (1H, m), 7,07 (1H, users), 7,22-to 7.50 (2H, m), 8,03-with 8.05 (1H, m), 8,42-8,46 (1H, m), 8,63-8,66 (1H, m), 8,73 (1H, d, J=1.6 Hz), 9,37-9,43 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 371:

(2R)-1-(1-(6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-3H-benzoni the azole-5-yl)pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color in the same way as in example 369, or in accordance with the method or by combining with an ordinary method but using 4-(4-econsultancy-phenoxy)-5-fluoro-2-nitro-phenylamine obtained in example 259 (stage 1), and 1-(R)pyrrolidin-2-yl-ethanol.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 1,81-2,03 (3H, m), 2,02 (3H, s), 2,24 is 2.33 (1H, m), up 3.22 (2H, square, J=7,4 Hz), 3,38-of 3.46 (1H, m), 3.72 points-with 3.79 (1H, m), and 4.40 (1H, t, J=7.5 Hz), 7,10 for 7.12 (3H, m), 7,29 (1H, ), 7,45-of 7.48 (1H, m), 7,87-of 7.90 (2H, m), of 7.90-7,98 (1H, m), 8,24 (1H, d, J=7,6 Hz), 8,72 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 491[M+H]

Example 372:

(2R)-1-(1-(6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color in the same way as in example 369, or in accordance with the method or by combining with an ordinary method but using 4-(4-econsultancy-phenoxy)-5-fluoro-2-nitro-phenylamine obtained in example 259 (stage 1), and 1-(R)pyrrolidin-2-yl-ethanol.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 1,82-2,04 (3H, m), 2,04 (3H, s), 2,24-of 2.34 (1H, m), up 3.22 (2H, square, J=7,4 Hz), 3,34-3,50 (1H, m), 3,70-with 3.79 (1H, m), of 4.38-4,48 (1H, m), 7,00-7,38 (4H, m), 7,89 (2H, d, J=9.0 Hz), 8,66 (1H, users), is 8.75 (1H, DD, J=1,6, 2,5 Hz), 9,38-9,48 (1H, m)

ESI-MS (m/e): 492[M+H]

Example 373:

(2R)-1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)who irreligion-2-yl)propan-1-ol

Specified in the title compound obtained as solid light yellow color in the same way as in example 369, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and 1-(R)pyrrolidin-2-yl-propanol.

1H NMR (CD3OD) δ: of 0.93 (3H, t, J=7.2 Hz), 1,25-of 1.27 (3H, m), 1,75-2,00 (3H, m), 2,23 of $ 2.53 (3H, m), 3.33 and - 3,44 (3H, m), 3,71 (2H, square, J=7,3 Hz), 4,43 (1H, t, J=7,6 Hz), 7,14 (1H, s), 7,38 (1H, s), 7,45 is 7.50 (2H, m,), to 7.93 - 8,00 (1H, m), of 8.06 (1H, d, J=8,8 Hz), of 8.25 (1H, d, J=8.0 Hz), to 8.45 (1H, d, J=2,9 Hz), 8,73 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 506[M+H]

Example 374:

(2R)-2-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)-ol-2-ol

Specified in the header of the connection will receive the same manner as in example 369, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenylamine obtained in example 221 (step 2), and (R)-1-methyl-1-(2-pyrrolidinyl)ethanol.

1H NMR (CD3OD) δ: of 0.85 and 0.87 (total 6H, each s)to 1.22 (3H, t, J=7,3 Hz), 1,59-of 1.84 (3H, m), 1.93 and-2,05 (1H, m), is 3.08-3,17 (1H, m), 3,31 is 3.40 (2H, m), 3,53-3,61 (1H, m), 4,00-a 4.03 (1H, m), 7,43-to 7.64 (4H, m), to $ 7.91-7,98 (1H, m,), 8,02 (1H, d, J=8,8 Hz), of 8.25 (1H, d, J=7.8 Hz), to 8.45 (1H, d, J=2.7 Hz), 8,71-8,73 (1H, m)

ESI-MS (m/e): 508[M+H]

Example 375:

(2R,4R)-4-hydroxy-1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-the l-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide

Specified in the title compound obtained as solid light yellow color in the same manner as in example 15, or in accordance with the method or by combining with an ordinary method but using CIS-4-hydroxy-D-prolinamide.

1H NMR (CD3OD) δ: 1,94 is 2.00 (1H, m), 2,50 at 2.59 (1H, m), 3,11 (3H, s), 3,38-3,44 (1H, m), of 3.73-of 3.77 (1H, m), 4,23-to 4.28 (1H, m), 4,36 was 4.42 (1H, m), 7,12 (2H, d, J=9.0 Hz), 7,24 (1H, s), 7,33 (1H, s), 7,44-7,47 (1H, m), 7,89-of 7.97 (3H, m), 8,21-8,24 (1H, m), 8,70-8,72 (1H, m)

ESI-MS (m/e): 494[M+H]

Example 376:

(2R,4S)-4-fluoro-1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide

Specified in the title compound obtained as solid light yellow color in the same way as in example 356, or in accordance with the method or by combining with an ordinary method, but using (2R,4R)-4-hydroxy-1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide, obtained in example 375.

1H NMR (CD3OD) δ: 2,01-of 2.21 (1H, m), 2,54-to 2.67 (1H, m), of 3.13 (3H, s), of 3.48 (1H, DD, J=12,8, 27,2 Hz), 4.09 to (1H, DDD, J=3,6, 12,8, and 39.7 Hz), 4,48 (1H, DD, J=6,4, 10,0 Hz), 5,20-of 5.34 (1H, m), to 7.15 (2H, d, J=8,8 Hz), 7,25 (1H, users), 7,41 (1H, users), 7,46-7,49 (1H, m), 7,92-to 7.99 (3H, m), compared to 8.26 (1H, d, J=8.0 Hz), 8,73 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 496[M+H]

Example 377:

(2R,4S)-4-hydroxy-1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-carboxamide

Specified in the header with the unity gain in the form of a solid of light yellow color in the same way, as in example 15, or in accordance with the method or by combining with an ordinary method, but using TRANS-4-hydroxy-D-prolinamide.

1H NMR (CD3OD) δ: 2,00-2,07 (1H, m), 2,33-2,39 (1H, m), of 3.13 (3H, s)of 3.25 (1H, d, J=10,8 Hz), 4,00 (1H, DD, J=4,1, to 10.8 Hz), of 4.44-4,50 (2H, m), 7,14 (2H, d, J=9.0 Hz), 7.23 percent (1H, users), 7,37 (1H, users), 7,46-7,49 (1H, m,), 7,92-to 7.99 (3H, m), of 8.25 (1H, dJ=8.0 Hz), 8,73 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 494[M+H]

Example 378:

1-((2R,4R)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-4-hydroxy-pyrrolidin-2-yl)alanon

(Stage 1) Obtaining methoxy-methyl-amide (2R,4R)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-4-hydroxy-pyrrolidin-2-carboxylic acid:

Specified in the title compound obtained as solid light yellow color in the same way as in example 369, or in accordance with the method or by combining with an ordinary method but using methoxy-methylamide (2R,4R)-4-hydroxy-pyrrolidin-2-carboxylic acid obtained in comparative example 5.

(Stage 2) Obtaining 1-((2R,4R)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-4-hydroxy-pyrrolidin-2-yl)alanon:

0,360 ml metallyte (a 1.0 M solution in diethyl simple ether) is added at -78°C to a solution in tetrahydrofuran (1 ml) 20 mg of methoxy-methyl-amide (2R,4R)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazol the-5-yl)-4-hydroxy-pyrrolidin-2-carboxylic acid, obtained (stage 1). The reaction liquid was stirred at -78°C for 1 hour, warmed to 0°C and stirred for 1 hour. Aqueous saturated solution of ammonium chloride is added to the reaction liquid, extracted it with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 1,79-of 1.88 (1H, m), of 2.08 (3H, s), 2,43-of 2.54 (1H, m)to 3.33 (2H, square, J=7,4 Hz), 3.46 in-3,63 (2H, m), 4,34-4,43 (2H, m), 7,10 (1H, users), 7,39 (1H, users), 7,43-to 7.50 (2H, m), 7,93-7,97 (1H, m), of 8.04 (1H, d, J=8,8 Hz), 8,23 (1H, d, J=8.0 Hz), 8,46 (1H, d, J=2.7 Hz), 8,71 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 508[M+H]

Example 379:

1-((2R,4S)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-4-fluoro-pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color in the same way as in example 356, or in accordance with the method or by combining with an ordinary method but using 1-((2R,4R)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)-4-hydroxy-pyrrolidin-2-yl)ethanone obtained in example 378.

1H NMR (CDCl3) δ : to 1.31 (3H, t, J=7.4 Hz), 1,80-2,05 (1H, m), 1.96 and 2,02 (total 3H, each s), and 2.26-2,60 (1H, m), 3,30-of 3.43 (2H, m), 3,43-3,66 (1H, m), 3,70-Android 4.04 (1H, m), 4,50 with 4.64 (1H, m), 5,12 lower than the 5.37 (1H, m), 6.90 to-7,56 (4H, m), 7,80-to $ 7.91 (1H, m), 7,93-8,02 (1H, m), 8.30 to-8,68 (3H, m)

ESI-MS (m/e): 510[M+H]

Example 380:

1-((2R,4S)-1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)-4-fluoro-pyrrolidin-2-yl)alanon

Specified in the title compound obtained as solid light yellow color in the same way as in example 370, example 378 (stage 2) and example 356, or in accordance with the method or by combining with an ordinary method but using methoxy-methylamide (2R,4R)-4-hydroxy-pyrrolidin-2-carboxylic acid obtained in comparative example 5.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 1,98-of 2.20 (1H, m), is 2.05 (3H, s), 2,48-2,61 (1H, m)to 3.41 (2H, square, J=7,4 Hz), of 3.56 (1H, DD, J=11,9 and 24.5 Hz), 3,99 (1H, DDD, J=3,1, 11,9, 39,1 Hz)and 4.65 (1H, DD, J=6,6, 10,3 Hz), 5,22 and 5.36 (1H, m), 7,13 (1H, users), of 7.48-to 7.50 (2H, m), with 8.05 (1H, DD, J=0,6, 8,8 Hz), charged 8.52 (1H, d, J=2,8 Hz), 8,67 (1H, d, J=2.5 Hz), 8,76 (1H, DD, J=1,4, 2,5 Hz), 9,43 (1H, d, J=1.4 Hz)

ESI-MS (m/e): 511[M+H]

Example 381:

5-(2-Fluoro-phenoxy)-2-pyridin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-who and Jethro-phenylamine, obtained in example 14, 2-terfenol.

1H NMR (CD3OD) δ: 3,10 (3H, s), 6,98-7,05 (1H, m), 7,07-7,21 (5H, m), 7,21-7,66 (3H, m), 7,88 (2H, d, J=9.0 Hz), 7,98 (1H, t, J=7,6 Hz), of 8.28 (1H, d, J=8,2 Hz), a total of 8.74 (1H, s)

ESI-MS (m/e): 476[M+H]

Example 382:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 5-(4-methanesulfonyl-phenoxy)-4-(2-fluoro-phenoxy)benzene-1,2-diamine obtained in example 381.

1H NMR (CD3OD) δ: 3,11 (3H, s), 7,00-was 7.08 (1H, m), 7,08-of 7.70 (5H, m), 7,11 (2H, d, J=8,8 Hz), of 7.90 (2H, d, J=8,8 Hz), 8,71 (1H, s), 8,78 (1H, s), for 9.47 (1H, s)

ESI-MS (m/e): 477[M+H]

Example 383:

5-(2,3-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method, but using 2,3-differenoe.

1H NMR (CD3OD) δ: 3,20 (3H, s), 6,79-6,83 (1H, m), 6,98 for 7.12 (2H, m), 7,17-7,80 (4H, m), 7,98-with 8.05 (2H, m), 8,27-8,35 (1H, m), 8,39 (1H, d, J=2.7 Hz), 8,64-8,79 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 384:

5-(2,4-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazo the l

Specified in the title compound obtained as solid light yellow color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method, but using 2,4-differenoe.

1H NMR (CD3OD) δ: is 3.21 (3H, s), 6,91-7,41 (4H, m), 7,47 to 7.75 (3H, m), 7,98-of 8.06 (2H, m), 8,27-of 8.33 (1H, m), 8,40-to 8.45 (1H, m), 8,66-8,76 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 385:

5-(2,5-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method, but using 2,5-differenoe.

1H NMR (CD3OD) δ: 3,20 (3H, s), 6,85-to 6.95 (2H, m), 7,24 (1H, TD, J=9,6, 5,1 Hz), 7,53 (1H, s), 7,56 (1H, DD, J=8,6, 2.7 Hz), to 7.64 (1H, DD, J=7,8, 4,7 Hz), 7,81 (1H, s), with 8.05 (1H, d, J=8.6 Hz), 8,10 (1H, t, J=7,8 Hz), with 8.33 (1H, d, J=7.8 Hz), 8,43 (1H, d, J=2.7 Hz), 8,84 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 495[M+H]

Example 386:

5-(2,6-Debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method, but using 2,6-differenoe.

p> 1H NMR (CD3OD) δ: 3,22 (3H, s), 7,09-7,17 (2H, m), 7,14 (2H, t, J=8,2 Hz), 7,26-to 7.32 (1H, m), 7,47-7,52 (1H, m), 7,55 (1H, DD, J=9,0, 2.3 Hz), 7,98 (1H, t, J=7.8 Hz), 8,07 (1H, d, J=9.0 Hz), of 8.27 (1H, d, J=7,8 Hz), 8,51 (1H, d, J=2.3 Hz), 8,72-a total of 8.74 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 387:

5-(2,5-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 4-(2,5-debtor-phenoxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 385.

1H NMR (CD3OD) δ: is 3.21 (3H, s), 6.75 in-6,92 (2H, m), 7,17-7,24 (1H, m), 7,35-a 7.85 (2H, m), 7,52 (1H, DD, J=8,6, 2.7 Hz), of 8.04 (1H, d, J=8.6 Hz), to 8.41 (1H, d, J=2.7 Hz), 8,73 (1H, s), 8,79 (1H, s), 9,50 (1H, s)

ESI-MS (m/e): 496[M+H]

Example 388:

5-(3,4-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 383, and the example 387, or in accordance with the method or by combining with an ordinary method, but using 3,4-differenoe.

1H NMR (CD3OD) δ: 3,18 (3H, s), of 6.65 (1H, users), to 6.80 (1H, users), 7,17 (1H, square, J=9.4 Hz), 7,46 (1H, DD, J=8,6, 2.7 Hz), 7,49-7,80 (2H, m), of 8.00 (1H, d, J=8.6 Hz), with 8.33 (1H, d, J=2.7 Hz), 8,69 (1H, s), 8,76 (1H, s), 9,46 (1H, s)

ESI-MS(m/e): 496[M+H]

Example 389:

5-(3,5-Debtor-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 388, or in accordance with the method or by combining with an ordinary method, but using 3,5-differenoe.

1H NMR (CD3OD) δ: 3,22 (3H, s), 6,41-of 6.49 (2H, m), 6,60-6,69 (1H, m)to 7.50 (1H, DD, J=8,6, 2.7 Hz), 7,54-of 7.82 (2H, m), of 8.04 (1H, d, J=8.6 Hz), at 8.36 (1H, d, J=2.7 Hz), a total of 8.74 (1H, users), 8,80 (1H, users), 9,52 (1H, s)

ESI-MS (m/e): 496[M+H]

Example 390:

5-(2-Deformationen-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-(5-methyl-pyrazin-2-yl)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 38, or in accordance with the method or by combining with an ordinary method but using 4-(2-deformedarse-pyridine-3-yloxy)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 215, and 5-methyl-pyrazin-2-carboxylic acid.

1H NMR (CD3OD) δ: to 2.65 (3H, s)3,18 (3H, s), to 7.15 (1H, DD, J=8.0 a, a 4.9 Hz), 7,32-7,80 (2H, m), 7,40 (1H, d, J=7,4 Hz), was 7.45 (1H, DD, J=8,8, 2.7 Hz), 7,46 (1H, t, J=72,6 Hz), to 7.93 (1H, DD, J=4,9, 1,4 Hz), 8,01 (1H, DD, J=8,8, 0.6 Hz), 8,35 (1H, DD, J=2.7, and 0.6 Hz), 8,67 (1H, d, J=1.0 Hz), to 9.32 (1H, d, J=1.3 Hz)

ESI-MS (m/e): 541[M+H]

Example 391:

5-Phenoxy-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yl) - Rev. XI)-1H-benzimidazole

(Stage 1) preparation of (5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenyl)-amide pyrazin-2-carboxylic acid:

3.8 g of pyrazin-2-carboxylic acid, 4.1 g of 1-hydroxybenzotriazole and 5.8 g of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to the solution in dimethylformamide (75 ml) of 7.5 g of 3-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)phenylamine obtained in example 221 (step 1), and the reaction liquid was stirred overnight at room temperature. To the reaction liquid, water is added and the precipitate collected by filtration, obtaining 8.0 g of crude product. of 0.44 ml of fuming nitric acid are added to a solution in triperoxonane acid (35 ml) 3.6 g of the obtained crude product, and the reaction liquid was stirred overnight at room temperature and the solvent is evaporated under reduced pressure. To the residue water is added and the resulting precipitate is collected by filtration, getting listed at the beginning of the connection.

(Stage 2) Obtain 5-(2,5-debtor-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole:

15 mg 2.5-debtor-phenol and 28 mg of cesium carbonate are added to a solution of N-methylpyrrolidinone (0.5 ml) 26 mg (5-fluoro-4-(6-methanesulfonyl-pyridine-3-yloxy)-2-nitro-phenyl)-amide pyrazin-2-carboxylic acid obtained in (stage 1), and the reaction liquid was stirred at 90° C for 15 minutes, add 100 mg of the dihydrate of tin chloride (II) to the reaction mass. The reaction liquid was stirred at 90°C for 1 hour and add it to the ethyl acetate and aqueous saturated solution of sodium bicarbonate. The precipitate is removed by filtration, the solvent is evaporated under reduced pressure and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: of 1.23 (3H, U=7,2 Hz), 3,24-3,44 (2H, m), 6,82-6,92 (2H, m),? 7.04 baby mortality-to 7.18 (1H, m), 7,26-7,38 (3H, m), of 7.48-7,56 (2H, m), 8,03 (1H, d, J=8,4 Hz), scored 8.38 (1H, s), a total of 8.74 (1H, s), 8,81 (1H, s), of 9.51 (1H, )

ESI-MS (m/e): 474[M+H]

Example 392:

5-(Naphthalene-1-yloxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 391 (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenyl)the Ministry of foreign Affairs pyrazin-2-carboxylic acid, obtained in example 391, and naphthalene-1-ol.

1H NMR (CD3OD) δ: of 1.17 (3H, t, J=7.4 Hz), 3,29 (2H, square, J=7,4 Hz), for 6.81 (1H, d, J=7,6 Hz), 7,29-7,40 (3H, m), 7,45-7,49 (1H, m), 7,55 (1H, d, J=7,6 Hz), 7,56 (1H, s), 7,72 (1H, d, J=8.6 Hz), of 7.75 (1H, s), 7,83 (1H, d, J=8,2 Hz), 7,89 (1H, d, J=8.6 Hz), 8,17 (1H, d, J=3.0 Hz), to 8.70 (1H, DD, J=2,3, 1.2 Hz), 8,77 (1H, d, J=2.3 Hz), 9,48 (1H, d, J=1.2 Hz)

ESI-MS (m/e): 524[M+H]

Example 393:

5-(Naphthalene-2-yloxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same manner as in example 391 (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenyl)-amide pyrazin-2-carboxylic acid obtained in example 391, and naphthalene-2-ol.

1H NMR (CD3OD) δ: a 1.11 (3H, t, J=7,6 Hz), 3,24 (2H, square, J=7,6 Hz), 7,10 (1H, DD, J=8,8, 2,5 Hz), 7,16 (1H, users), 7,35-7,46 (3H, m)to 7.50 (1H, d, J=3.1 Hz), 7,52 (1H, d, J=2.5 Hz), to 7.67 (1H, d, J=8,2 Hz), 7,81 (1H with), 7,83 (1H, s), 7,95 (1H, d, J=6.3 Hz), a 8.34 (1H, d, J=2.3 Hz), 8,73 (1H, d, J=2.7 Hz), 8,80 (1H, DD, J=2.7, and 1.6 Hz), 9,52 (1H, d, J=1,6 Hz)

ESI-MS (m/e): 524[M+H]

Example 394:

5-(2-Deformity-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 221 (step 3), or in accordance with the method, or merge the receiving conventional way, but using 2-deformity-phenol.

1H NMR (CD3OD) δ: to 1.21 (3H, t, J=8,4 Hz), 3,37 (2H, square, J=8,4 Hz), 6,72 (1H, t, J=59,8 Hz), 6,85-of 6.90 (1H, m), 7,17 (1H, t, J=8.6 Hz), 7,39-7,46 (3H, m), 7,51-to 7.84 (3H, m), 7,98-with 8.05 (2H, m), 8,31-8,39 (2H, m), 8,65 cent to 8.85 (1H, m)

ESI-MS (m/e): 523[M+H]

Example 395:

5-(2-Carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 196.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7,3 Hz), 3,37 (2H, square, J=7,3 Hz), to 6.88 (1H, d, J=8,2 Hz), 7,16 (1H, t, J=7.4 Hz), 7,40-7,46 (2H, m), 7,51-rate of 7.54 (1H, m), of 7.64 (1H, users), of 7.70 (1H, users), 7,87 (1H, d, J=7.8 Hz), 7,98 (1H, d, J=8.6 Hz), 8,01 (1H, t, J=8.6 Hz), 8,30 (1H, d, J=2.7 Hz), with 8.33 (1H, d, J=7.8 Hz), 8,76 (1H, users)

ESI-MS (m/e): 516[M+H]

Example 396:

5-Benzyloxy-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same way as in example 250, or in accordance with the method or by combining with an ordinary method but using 4-benzyloxy-3-foronline obtained in example 250 (stage 1), pikolinos acid and 6-econsultancy-pyridine-3-the La.

1H NMR (CDCl3) δ: of 1.26 (3H, t, J=7,6 Hz), the 3.35 (2H, square, J=7,6 Hz), 5,07 (2H, s), 7,10-7,13 (2H, m), to 7.15 (1H, s), 7,26-7,27 (4H, m), 7,34-7,39 (1H, m), 7,51 (NH/2, C)of 7.64 (NH/2, p), 7,83-7,86 (1H, m), 7.95 is-of 7.96 (1H, m), 8,33-8,35 (1H, m), 8,45-8,46 (1H, m), 8,60-8,63 (1H, m), 10,43-10,46 (1H, m)

ESI-MS (m/e): 487[M+H]

Example 397:

5-(2-Methanesulfonyl-6-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

(Stage 1) preparation of 5-hydroxy-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole:

Specified in the title compound obtained as solid light green color in the same way as in example 251 (stage 1), or in accordance with the method or by combining with an ordinary method but using 5-benzyloxy-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 396.

(Stage 2) Obtain 5-(2-methanesulfonyl-6-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole:

Specified in the title compound obtained as solid light green color in the same way as in example 251, or in accordance with the method or by combining with an ordinary method but using 5-hydroxy-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in (stage 1), and 1,2-debtor-3-methanesulfonyl-benzene.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), of 2.97 (3H, s)to 3.41 (2H, square, J7,4 Hz), 7,11 (1H, s), 7,50-EUR 7.57 (2H, m), to 7.61-of 7.70 (2H, m), of 7.70 (1H, s), 7,87 (1H, d, J=8.0 Hz), to 7.99 (1H, t, J=8.0 Hz), 8,10 (1H, d, J=8.6 Hz), of 8.27 (1H, d, J=7,0 Hz), to 8.57 (1H, d, J=2.7 Hz), a total of 8.74 (1H, d, J=the 4.3 Hz)

ESI-MS (m/e): 569[M+H]

Example 398:

5-(2-Fluoro-6-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light green color in the same way as in example 251, or in accordance with the method or by combining with an ordinary method but using 5-hydroxy-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 397, and 1,2-debtor-3-cyano-benzene.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 7,27-the 7.43 (1H, m), 7,40 (1H, TD, J=8,0, 4.6 Hz), 7,49-of 7.55 (2H, m), 7,56-7,76 (3H, m), to 7.99 (1H, t, J=7,6 Hz), of 8.06 (1H, d, J=9.0 Hz), 8,30 (1H, d, J=7,6 Hz), 8,46 (1H, d, J=2.7 Hz), the rate of 8.75 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 516[M+H]

Example 399:

5-(2-Fluoro-6-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-fluoro-6-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 397.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 7,00-7,18 1H, m), 7,34-the 7.43 (2H, m), 7,49 (1H, users), 7,54-7,56 (2H, m), 7,66 (1H, users), of 7.97 (1H, t, J=8.0 Hz), 8,07 (1H, d, J=8.6 Hz), 8,20-8,30 (1H, m), 8,53 (1H, d, J=2.7 Hz), 8,70-8,77 (1H, m)

ESI-MS (m/e): 534[M+H]

Example 400:

5-(2-Fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole

(Stage 1) preparation of 3-fluoro-4-(2-fluoro-6-cyano-phenoxy)-phenylamine:

Specified in the header of the connection will receive the same manner as in example 221 (step 1), or in accordance with the method or by combining with an ordinary method, but using tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in example 196 (step 1), and 1,2-debtor-3-cyano-benzene.

(Stage 2) Getting (5-fluoro-4-(2-fluoro-6-cyano-phenoxy)-2-nitro-phenyl)amide pyrazin-2-carboxylic acid:

Specified in the header of the connection will receive the same manner as in example 391 (stage 1), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(2-fluoro-6-cyano-phenoxy)phenylamine obtained in stage 1, and pyrazin-2-carboxylic acid.

(Stage 3) Obtain 5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole:

Specified in the header of the connection get in a solid brown color in the same manner as in example 391 (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(2-fluoro-6-C the ANO-phenoxy)-2-nitro-phenyl)amide pyrazin-2-carboxylic acid, obtained in stage 2, and 4-econsultancy-phenol.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 3,20 (2H, square, J=7,4 Hz), 7,12 (2H, d, J=9.0 Hz), 7,33-7,40 (2H, m), 7,55 to 7.62 (3H, m), 7,86 (2H, d, J=9.0 Hz), 8,72 (1H, s), 8,78 (1H, s), 9,48 (1H, s)

ESI-MS (m/e): 516[M+H]

Example 401:

5-(2-Fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole and

5-(2-fluoro-6-isopropylcarbamate-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole

Listed in the connection header get in a solid brown and solid light green color, respectively, in the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole obtained in example 400.

5-(2-Fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), up 3.22 (2H, square, J=7,4 Hz), 7,00-7,34 (1H, m), 7.23 percent (2H, d, J=8,8 Hz), 7,34-of 7.70 (4H, m), to $ 7.91 (2H, d, J=8,8 Hz), 8,71 (1H, s), 8,77 (1H, s), 9,46 (1H, s)

ESI-MS (m/e): 534[M+H]

5-(2-Fluoro-6-isopropylcarbamate-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole

1H NMR (CDCl3) δ: of 1.10 (6H, d, J=9.6 Hz), 1,24 (3H, t, J=7.4 Hz), 3,01-3,11 (2H, m), 4,06-4,16 (1H, m), 6,80-7,87 (9H, m), charged 8.52 at 8.60 (2H, m), 9,51-9,54 (1H, m), 10,78-10,80 (1H, m)

ESI-MS (m/e): 576[M+H]

Example 402:

5-(2-Fluoro-6-cyan is phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 400 (stage 3), or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(2-cyano-6-fluoro-phenoxy)-2-nitro-phenyl)-amide pyrazin-2-carboxylic acid obtained in example 400 (phase 2), and 6-econsultancy-pyridine-3-ol.

1H NMR (DMSO-d6) δ: of 1.10 (3H, t, J=7.4 Hz), 3.27 to to 3.36 (2H, m), 7,22-to 7.35 (1H, m), 7,38-to 7.50 (2H, m), 7,72-to 7.77 (3H, m), 7,98 (1H, d, J=9,0 Hz)and 8.50 (1H, d, J=2.7 Hz), 8,76 (1H, s), 8,79 (1H, s), to 9.45 (1H, s)

ESI-MS (m/e): 517[M+H]

Example 403:

5-(2-Fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole and 5-(2-fluoro-6-isopropylcarbamate-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Listed in the connection header receives each in the form of a colorless solid by the same method as in example 43 or in accordance with the method or by combining with an ordinary method but using 5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 402.

5-(2-Fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

1H NMR (CD3OD) δ: of 1.27 (3H, t, J=7.4 Hz), 3,43 (2H, square, J=7,4 Hz), 7,08-7,11 (1H, m), 7,38-7,46 (2H, m), 7,46-7,80 (3H, m), 8,10 (1H, d, J=4,7 Hz), 8,55 (1H, d, J=2.7 Hz), 8,71 (1H, s), 8,78 (1H, s),for 9.47 (1H, C)

ESI-MS (m/e): 535[M+H]

5-(2-Fluoro-6-isopropylcarbamate-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

1H NMR (CD3OD) δ: a 1.08 (6H, d, J=6.6 Hz), 1,25 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 3,94-was 4.02 (1H, m), 7,10 (1H, s), of 7.36-7,46 (3H, m), to 7.59 (1H, d, J=9.0 Hz), 7,74 (1H, s), 8,08 (1H, d, J=9.0 Hz), 8,56 (1H, s), is 8.75 (1H, s), 8,80 (1H, s), 9,44 (1H, s)

ESI-MS (m/e): 577[M+H]

Example 404:

5-(2-Fluoro-6-(tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 60, or in accordance with the method or by combining with an ordinary method but using 5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 402.

1H NMR (CD3OD) δ: of 1.27 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 7,37-7,46 (4H, m), 7,60 (1H, s), to 7.84 (1H, d, J=5,9 Hz), 7,94 (1H, d, J=9.0 Hz), 8,32 (1H, d, J=2.0 Hz), 8,71 (1H, s), 8,77 (1H, s), for 9.47 (1H with)

ESI-MS (m/e): 560[M+H]

Example 405:

5-(2-Methylsulfanyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 221 (step 3), or in accordance with the method or by combining with an ordinary method but using 2-methylsulfanyl-phenol.

1H NMR(CDCl 3) δ: of 1.28 (3H, t, J=7.4 Hz), to 3.38 (2H, square, J=7,4 Hz), 6,78 (1H, DDD, J=7,6, to 7.6, 1.5 Hz), 7.03 is for 7.12 (2H, m), 7,08 (1/2H, s), 7,16 (1H, d, J=7,6 Hz), 7,30 (1H, DD, J=8,7, 2,5 Hz), was 7.36 (1/2H,s), 7,37-7,41 (1H, m), 7,47 (1/2H, s), 7,72 (1/2H, s), 7,86-of 7.90 (1H, m), of 7.97 (1H, d, J=8.7 Hz), scored 8.38 (1H, d, J=2.5 Hz), scored 8.38-to 8.41 (1H, m), 8,61-8,63 (1H, m), 11,16 (1/2H, users), 11,28 (1/2H, users)

ESI-MS (m/e): 519[M+H]

Example 406:

5-(2-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole and 5-(2-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

2 ml of water and 89 mg of Oxone added to a solution in methanol (3 ml), 46 mg of 5-(2-methylsulfanyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole obtained in example 405, and the reaction liquid was stirred at room temperature for 5 hours. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the header of each connection in the form of a solid of light yellow color.

5-(2-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7,6 Hz), 2,59 (3/2H, s), 2.63 in (3/2H, s)to 3.38 (2H, square, J=7,6 Hz), 6,78-for 6.81 (1H, m), 7,25-7,33 (2H, m), 7,35-the 7.43 (1H, m), 7,08 (1/2H, s), 7,16 (1H, d, J=7,6 Hz), 7,30 (1H, DD, J=8,7, 2,5 Hz), was 7.36 (1/2H,s), 7,37-7,41 (1H, m), 7,47 (1/2H, s), 7,72 (1/2H, s), 7,86-of 7.90 (1H,m), of 7.97 (1H, d, J=8.7 Hz), scored 8.38 (1H, d, J=2.5 Hz), scored 8.38-to 8.41 (1H, m), 8,61-8,63 (1H, m), 11,16 (1/2H, users), 11,28 (1/2H, users)

ESI-MS (m/e): 535[M+H]

5-(2-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), 2,95 (3/2H, s)3,02 (3/2H, s)to 3.36 (2H, square, J=7,4 Hz), 6,92-6,97 (1H, d), 7,20-7,27 (1H, m), 7,31-7,35 (3/2H, m), 7,41-7,45 (3/2H, m), 7,51-EUR 7.57 (1H, m), 7,65 (1/2H, s), 7,72 (1/2H, s), 7,87-a 7.92 (1H, m), 7,97-of 8.04 (2H, m), 8.34 per-8,42 (2H, m), 8,65-8,67 (1H, m), of 10.72 (1H, users)

ESI-MS (m/e): 551[M+H]

Example 407:

5-(2-Bromopyridin-3-yloxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 391, or in accordance with the method or by combining with an ordinary method but using 5-fluoro-4-(6-econsultancy-pyridine-3-yloxy)-2-nitro-phenyl)amide pyrazin-2-carboxylic acid obtained in example 391, and 2-bromo-pyridine-3-ol.

1H NMR (CDCl3) δ: of 1.30 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 7,03 (1H, DD, J=8.0 a, 1,6 Hz), 7,19-7,22 (1H, m), 7,28-to 7.32 (1H, m), 7,34 (1/2H, users), 7,51 (1/2H, users), 7.62mm (1/2H, users), to 7.93 (1/2H, users), 8,00 (1H, d, J=8.6 Hz), 8,14 (1H, users), 8,31-8,32 (1H, m), to 8.62 (1H, users), to 8.70 (1H, d, J=2.4 Hz), for 9.64 (1H, users), 10,91 (1/2H, users), 10,98 (1/2H, users)

ESI-MS (m/e): 553[M+H]

Example 408:

5-(2-Vinylpyridin-3-yloxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header is VCE connection receive in the form of a solid of light yellow color in the same way, as in example 407, or in accordance with the method or by combining with an ordinary method but using 2-vinyl-pyridine-3-ol.

1H NMR (CDCl3) δ: of 1.27 (3H, t, J=7.5 Hz), 3,37 (2H, square, J=7.5 Hz), of 5.34 (1H, DD, J=10,9, 1.9 Hz), 6,30 (1H, DD, J=17.4 years, and 1.9 Hz), 6,72 (1H, DD, J=17.4 years, up 10.9 Hz), to 7.09 (1H, DD, J=8,2, 1.5 Hz), 7,12 (1H, DD, J=8,2, a 4.3 Hz), 7,27 (1H, DD, J=8,7, 2,9 Hz), 8,00 (1H, d, J=8.7 Hz), 8,31 (1H, d, J=2,9 Hz), with 8.33 (1H, DD, J=4,3, 1.5 Hz), 8,61 (1H, DD, J=2,6, and 1.6 Hz), 8,69 (1H, d, J=2.6 Hz), or 10.60 (1/2H, users), is 10.68 (1/2H, users)

ESI-MS (m/e): 501[M+H]

Example 409:

5-(2-Cyclopropyl-pyridine-3-yloxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 407, or in accordance with the method or by combining with an ordinary method but using 2-cyclopropyl-pyridine-3-ol.

1H NMR (CDCl3) δ: 0,77-1,02 (2H, m), of 1.24 to 1.31 (2H, m)of 1.29 (3H, t, J=7.4 Hz), 3,37 (2H, square, J=7,4 Hz), of 6.96 (2/5H, DD, J=8,2, 4.6 Hz), 6,98 (3/5H, DD, J=8,2, 4.6 Hz), 7,03 (2/5H, DD, J=8,2, 1.5 Hz),? 7.04 baby mortality (3/5H, DD, J=8,2, 1.5 Hz), 7,16 (1/2H, s), 7,33 (1H, DD, J=8,8, 3.0 Hz), of 7.48 (1/2H, s), 7,53 (1/2H, s), 7,78 (1/2H, s), of 8.00 (1H, d, J=8,8 Hz), 8,20 (2/5H, DD, J=4,6, 1.5 Hz), by 8.22 (3/5H, DD, J=4,6, L5 Hz), 8,39 (2/5H, d, J=3.0 Hz), 8,40 (3/5H, d, J=3.0 Hz), 8,59-to 8.62 (1H, m), 8,68-to 8.70 (1H, m), 9,62-for 9.64 (1H, m), or 10.60 (3/5H, users), 10,66 (2/5H, users)

ESI-MS (m/e): 515[M+H]

Example 410:

5-(2-Deformationen-3-yloxy)-2-pyridin-2-yl-6-(4-dimethylsulphamoyl-phenoxy)-1H-benzimidazole

Listed is in the title compound obtained as solid light yellow color in the same way, as in example 221 (stage 1)-(stage 3), or in accordance with the method or by combining with an ordinary method but using 4-(N,N-dimethylaminomethyl)-phenol and 2-deformedarse-pyridine-3-ol.

1H NMR (CD3OD) δ: of 2.66 (6H, s), 7,05 (2H, d, J=8.6 Hz), 7,10-7,19 (1H, m), 7,32 to 7.62 (4H, m), 7,49 (1H, t, J=72,8 Hz), 7,71 (2H, d, J=8.6 Hz), to $ 7.91 (1H, d, J=4,1 Hz), 8,01 (1H, t, J=7.8 Hz), 8,32 (1H, d, J=a 7.6 Hz), 8,77 (1H, s)

ESI-MS (m/e): 554[M+H]

Example 411:

5-(2-Deformationen-3-yloxy)-6-(3-chloro-4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 221 (stage 1)-(stage 3), or in accordance with the method or by combining with an ordinary method but using 4-methanesulfonyl-3-chloro-phenol and 2-deformedarse-pyridine-3-ol.

1H NMR (CD3OD) δ: of 3.25 (3H, s), 6,98 (1H, DD, J=8,6, and 2.3 Hz), to 7.09 (1H, d, J=2.3 Hz), to 7.15 (1H, DD, J=7,8, and 4.9 Hz), 7,35-7,46 (2H, m), 7,46-7,74 (3H, m), of 7.48 (1H, t, J=74,0 Hz), to $ 7.91-7,94 (1H, m), 8,02 (1H, d, J=8.6 Hz), 8,32 (1H, d, J=7.8 Hz), 8,75-8,77 (1H, m)

ESI-MS (m/e): 552[M-H]

Example 412:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(4-(N-hydroxycarbamoyl)phenoxy)-1H-benzimidazole

0.5 ml hydroxylamine (50% aqueous solution) are added to a solution in ethanol (0.5 ml) 6.0 mg of 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-cyano-pyridine-3-yloxy)-1H-benzimidazole obtained in example 252, and the reaction liquid was stirred at to the room temperature for 3 hours. Then the solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CD3OD) δ: 7,01? 7.04 baby mortality (1H, m), 7,10-7,22 (3H, m), 7,29-to 7.35 (2H, m), 7,60 (1H, s), 7,82 (1H, d, J=9.0 Hz), 8,24 (1H, d, J=2.3 Hz), to 8.70 (1H, d, J=1.6 Hz), 8,77 (1H, d, J=1.6 Hz), 9,48 (1H, s)

ESI-MS (m/e): 458[M+H]

Example 413:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-(5-methyl-[1,2,4]oxadiazol)-3-yloxy)-1H-benzimidazole

The solution in acetic anhydride (1 ml) 3.6 mg of 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(4-(N-hydroxycarbamoyl)phenoxy)-1H-benzimidazole obtained in example 412, stirred over night at 60°C. the Solvent is evaporated under reduced pressure and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. The solvent of the resulting fraction is diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as a colourless solid.

1H NMR (CD3OD) δ: 2,69 (3H, s), 7,00-7,40 (5H, m), of 7.48 (1H, DD, J=7,8, and 2.3 Hz), 7,52-a 7.85 (1H, m), 8,10 (1H, d, J=7.8 Hz), of 8.37 (1H, d, J=2.3 Hz), 8,71 (1H, s), 8,78 (1H, s), 9,48 (1H, s)

ESI-MS (m/e): 482[M+H]

Example 414:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-(5-tripto the methyl-[1,2,4]oxadiazol)-3-yloxy)-1H-benzimidazole

Solution in triperoxonane anhydride (1 ml) 2.0 mg of 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(4-(N-hydroxycarbamoyl)phenoxy)-1H-benzimidazole obtained in example 412, stirred at 60°C for 1 hour. The solvent is evaporated under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound as a colourless solid.

1H NMR (CD3OD) δ: 7,00-to 7.50 (5H, m), 7,55 (1H, DD, J=7,8 Hz, 2.3 Hz), 7,60-7,80 (1H, m), by 8.22 (1H, d, J=7.8 Hz), to 8.45 (1H, d, J=2.3 Hz), 8,73 (1H, s), 8,80 (1H, s), 9,50 (1H, s)

ESI-MS (m/e): 536[M+H]

Example 415:

5-(2-Fluoro-phenoxy)-2-pyrazin-2-yl-6-(imidazo[1,2-a]pyridine-6-yloxy)-1H-benzimidazole

Stage (1) preparation of 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-nitro-pyridine-3-yloxy)-1H-benzimidazole:

Specified in the header of the connection will receive the same manner as in example 251 (stage 2), or in accordance with the method or by combining with an ordinary method but using 2-nitro-5-pyridine.

(Stage 2) Obtain 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(imidazo[1,2-a]pyridine-6-yloxy)-1H-benzimidazole:

The catalyst of the Raney Nickel with a developed surface are added to a solution in methanol (0.5 ml) 12 mg of 5-(2-fluoro-phenoxy)-2-pyrazin-2-yl-6-(6-nitro-pyridine-3-yloxy)-1H-benzimidazole obtained in (stage 1), and the reaction liquid displaced is more in the atmosphere of hydrogen for 1 hour. The catalyst was removed by filtration and the solvent is evaporated under reduced pressure. 0,02 ml chloroacetaldehyde (40% aqueous solution) are added to a solution in ethanol (0.3 ml) of the obtained residue, and the reaction liquid was stirred overnight at room temperature. The solvent is evaporated under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound in the form of solid light yellow color.

1H NMR (CDCl3) δ: of 1.25 (3H, t, J=7.0 Hz), to 3.73 (2H, square, J=7,0 Hz), 7,00-7,22 (6H, m), 7,31-the 7.65 (4H, m), 7,82 (1/2H, s), 7,88 (1/2H, s), to 8.57 (1H, DD, J=2.5 and 1.5 Hz), 8,64 (1H, s), 9,59 (1H, s), 10,57 (1/2H, users), 10,97 (1/2H, users)

ESI-MS (m/e): 439[M+H]

Example 416:

5-(Pyridine-2-ylsulphonyl)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same manner as in example 391 (stage 2), or in accordance with the method or by combining with an ordinary method but using pyridine-2-thiol.

1H NMR (CD3OD) δ: of 1.23 (3H, t, J=7.4 Hz), to 3.36 (2H, square, J=7,4 Hz), 7,07 (1H, d, J=8,2 Hz), 7,11 (1H, DD, J=7,4, a 4.9 Hz), 7,41 (1H, d, J=7,6 Hz), 7,58-7,80 (1H, m), 7,60 (1H, TD, J=7,6, 1.8 Hz), 7,95 (1H, DD, J=8,6, 0.6 Hz), 8,00 is 8.25 (1H, m), of 8.28 (1H, DD, J=5,1, 1.0 Hz), with 8.33 (1H, d, J=0.6 Hz), the rate of 8.75 (1H, d, J=2.5 Hz), 8,82 (1H, DD, J=2.5 and 1.5 Hz), at 9.53 (1H, d, J=1,5 is C)

ESI-MS (m/e): 491[M+H]

Example 417:

5-(3-Cyano-pyridine-2-ylsulphonyl)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same manner as in example 391 (stage 2), or in accordance with the method or by combining with an ordinary method but using 3-cyano-pyridine-2-thiol.

1H NMR (CDCl3) δ: of 1.29 (3H, t, J=7.4 Hz), to 3.36 (2H, square, J=7,4 Hz), was 7.08 (1H, DD, J=7,8, and 4.9 Hz), 7,35 (1H, DD, J=8,6, 2,8 Hz), 7,35 and the 7.65 (total 1H, each s), 7,80 (1H, DD, J=7,8, 1.8 Hz), to 7.93 (1H, d, J=8,4 Hz), 7.95 and by 8.22 (total 1H, each s), at 8.36 (2H, d, J=2.5 Hz), 8,63 (1H, s)8,71 (1H, s), 9,65 (1H, d, J=1.4 Hz)

ESI-MS (m/e): 516[M+H]

Example 418:

5-(2-Chlorophenyl-sulfonyl)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 196 (stage 4)-(stage 6), or in accordance with the method or by combining with an ordinary method but using 2-chloro-thiophenol.

1H NMR (CD3OD) δ: 3,20 (3H, s), 7.03 is-7,10 (1H, m), 7,13-7,20 (2H, m), 7,34-7,39 (2H, m), 7,50-7,86 (3H, m), 7,94 (1H, d, J=8.6 Hz), 8,01 (1H, t, J=7.8 Hz), 8,29-8,35 (2H, m), 8,77 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 509[M+H]

Example 419:

4-(2-Cyano-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection receives the same way to the to in example 274, or in accordance with the method or by combining with an ordinary method but using 2-cyano-phenol and 6-econsultancy-pyridin-3-yl accordingly.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 6,78 (1H, s), 7,12 (1H, d, J=8.6 Hz), 7,29-7,31 (2H, m), 7,50-7,51 (1H, m), 7,63-the 7.65 (2H, m), 7,82 (1H, d, J=7,4 Hz), 7,95-of 7.97 (1H, m), 8,08 (1H, d, J=8.6 Hz), 8,32 (1H, d, J=8,2 Hz), 8,55 (1H, d, J=2.7 Hz), the rate of 8.75 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 498[M+H]

Example 420:

4-(2-Cyano-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-(2-cyano-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 419.

1H NMR (CD3OD) δ: of 1.27 (3H, t, J=8.0 Hz), 3,42 (2H, square, J=8.0 Hz), 6,79-6,84 (1H, m), 7,14-7,17 (1H, m), 7,31-to 7.35 (1H, m), to 7.61-to 7.68 (2H, m), 7,80-a 7.85 (2H, m), 8,08 (1H, d, J=8,4 Hz), 8,54-8,59 (1H, m), 8,70-8,73 (1H, m), 8,77-8,79 (1H, m), 9,48-9,50 (1H, m)

ESI-MS (m/e): 499[M+H]

Example 421:

4-(2-Cyano-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-(2-cyano-dryer is ISQ)-5-(6-methanesulfonyl-pyridine-3-yloxy)benzene-1,2-diamine, obtained in example 286.

1H NMR (CD3OD) δ: 3,24 (3H, s), 6,80-6,83 (1H, m), 7,72 (1H, d, J=8.6 Hz), 7,30 is 7.50 (2H, m), 7,60-7,80 (2H, m), 7,88 (1H, d, J=7.8 Hz), 8,11 (1H, d, J=9.0 Hz), 8,56 (1H, s), 8,73 (1H, s), 8,79 (1H, s), 9,50 (1H, s)

ESI-MS (m/e): 485[M+H]

Example 422:

4-(2,3-Debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 274, or in accordance with the method or by combining with an ordinary method, but using 2,3-debtor-phenol and 6-methanesulfonyl-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: 3,23 (3H, s)6,70 (1H, d, J=2.3 Hz), 7,12-of 7.25 (3H, m), 7,29 (1H, d, J=2.3 Hz), 7,60-the 7.65 (2H, m), 8.07-a 8,10 (2H, m), 8,39 (1H, d, J=7.9 Hz), and 8.50 (1H, d, J=3,4 Hz), 8,83 cent to 8.85 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 423:

4-(2,3-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 204 (stage 2), or in accordance with the method or by combining with an ordinary method but using 3-(2,3-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 285.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7,6 Hz), 3,40 (2H, square, J=7,6 Hz), of 6.71 (1H, d, J=2.0 Hz), 7,12-7,26 (3H, m), 7,30 (1H, d, J=2.0 Hz), 7,60-to 7.68 (2H, m), 8,06-8,13 (2H, m), 8,40 (1H, d, J=7,4 Hz), charged 8.52 (1H, d, J=2.7 Hz), 8,86 (1H, d, J=5,1 Hz)

ESI-MS (m/e): 509[M+H]

Example 424:

4-(2,5-Debtor-is enocsi)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 278, or in accordance with the method or by combining with an ordinary method, but using 2,5-debtor-phenol and 6-econsultancy-pyridine-3-ol.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=8,2 Hz), to 3.41 (2H, square, J=8,2 Hz), 6,59 (1H, s), 6,99-7,05 (1H, m), 7,06-7,14 (1H, m), 7,22 (1H, users), 7,34 (1H, TD, J=9,8, a 4.9 Hz), to 7.61 (1H, DD, J=8,6, a 4.3 Hz), 8,07 (1H, d, J=8,6 Hz), charged 8.52 (1H, d, J=4.3 Hz), 8,72 (1H, d, J=1.2 Hz), 8,79 (1H, s), 9,54 (1H, d, J=1.2 Hz)

ESI-MS (m/e): 510[M+H]

Example 425:

4-(2,5-Debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 204 (stage 2), or in accordance with the method or by combining with an ordinary method but using 3-(2,5-debtor-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 424.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.5 Hz), 3,40 (2H, square, J=7.5 Hz), 6,55 (1H, s), of 6.96-7,05 (1H, m), 7,05-7,14 (1H, m), 7,21 (1H, s), 7,28-7,38 (1H, m), 7,50-7,56 (1H, m), 7,56-7,63 (1H, m), 7,97-8,03 (1H, m), 8,07 (1H, d, J=8,2 Hz), scored 8.38 (1H, d, J=7,0 Hz), 8,51 (1H, s), 8,76 (1H, s)

ESI-MS (m/e): 509[M+H]

Example 426:

4-(2,6-Debtor-phenoxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 278, or ACC is accordance with the method, or Association with an ordinary method, but using 2,6-debtor-phenol and 4-econsultancy-phenol accordingly.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), 3,21 (2H, square, J=7,4 Hz), 6,37 (1H, users), 7,13-of 7.25 (5H, m), 7,34-7,39 (1H, m), 7,89 (2H, d, J=8,8 Hz), 8,78 (1H, d, J=2.7 Hz), 8,84 (1H, DD, J=1,6, 2.7 Hz), of 9.56 (1H, d, J=1,6 Hz)

ESI-MS (m/e): 509[M+H]

Example 427:

4-(2,6-Debtor-phenoxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 204 (stage 2), or in accordance with the method or by combining with an ordinary method but using 3-(2,6-debtor-phenoxy)-5-(4-econsultancy-phenoxy)benzene-1,2-diamine obtained in example 426.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 3,21 (2H, square, J=7,4 Hz), 6,23 (1H, users), was 7.08 (1H, users), 7,15-7,22 (4H, m), 7,28-7,38 (1H, m), 7,51 (1H, t, J=5,9 Hz), 7,87 (2H, d, J=9.0 Hz), 8,00 (1H, t, J=7.4 Hz), to 8.41 (1H, d, J=7,4 Hz), 8,76 (1H, users)

ESI-MS (m/e): 508[M+H]

Example 428:

4-(2-Deformity-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless solid in the same manner as in example 274, or in accordance with the method or by combining with an ordinary method but using 2-deformity-phenol and 6-econsultancy-pyridine-3-ol.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 6,50 (1 is, C)to 7.15 (1H, d, J=7,4 Hz), 7,22 (1H, t, J=55,5 Hz), 7,34 (1H, t, J=7.4 Hz), 7,49 to 7.62 (4H, m), 7,74 (1H, d, J=7,4 Hz), 7,98 (1H, t, J=7.4 Hz), with 8.05 (1H, d, J=8.6 Hz), of 8.37 (1H, d, J=7,4 Hz), 8,49 (1H, d, J=2.3 Hz), a total of 8.74-8,77 (1H, m)

ESI-MS (m/e): 523[M+H]

Example 429:

4-(2-Deformity-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-(2-deformity-phenoxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 428.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.8 Hz), 3,40 (2H, square, J=7.8 Hz), is 6.54 (1H, s), 7,17 (1H, d, J=7,4 Hz), 7,21 (1H, t, J=55,8 Hz), was 7.36 (1H, t, J=7.4 Hz), 7,50-the 7.65 (2H, m), of 7.75 (1H, d, J=7,4 Hz), of 8.06 (1H, d, J=8.6 Hz), 8,51 (1H, d, J=2.7 Hz), 8,72 (1H, s), 8,79 (1H, s), 9,54 (1H, s)

ESI-MS (m/e): 524[M+H]

Example 430:

4-(2-Deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 274, or in accordance with the method or by combining with an ordinary method but using 2-deformedarse-pyridine-3-ol and 4-econsultancy-phenol accordingly.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7,3 Hz), 3,40 (2H, square, J=7,3 Hz), 6,60 (1H, d, J=2.0 Hz), 7,27-7,30 (2H, m), EUR 7.57-7,6l (2H, m), of 7.64 (1H, t, J=72,1 Hz), 7,73 (1H, DD, J=7,8, and 1.6 Hz), 8,05-8,08 (2H, m), 8,10(1H, DD, J=4,9, 1,6 Hz), of 8.37 (1H, d, J=8,2 Hz), 8,51 (1H, d, J=2.7 Hz), 8,81 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 540[M+H]

Example 431:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-5-(4-econsultancy-phenoxy)benzene-1,2-diamine obtained in example 274 (stage 1).

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 3,21 (2H, square, J=7,4 Hz), the 3.65 (3H, s)6,38 (1H, t, J=7.2 Hz), 6,44 (1H, s), 7,07 (1H, s), 7,15-7,22 (2H, m), 7,40 (1H, d, J=7,0 Hz), EUR 7.57 (1H, DD, J=7,0, 1.8 Hz), 7,84-of 7.90 (2H, m), to 8.70 (1H, s), 8,76 (1H, s)9,52 (1H, s)

ESI-MS (m/e): 504[M+H]

Example 432:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solids in a light brown colour in the same way as in example 274, or in accordance with the method or by combining with an ordinary method but using 1-methyl-2-oxo-1,2-dihydro-pyridine-3-ol and 6-econsultancy-pyridine-3-ol.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), the 3.65 (3H, s), 6,36 (1H, t, J=6,7 Hz), 6,46 (1H, s), 7,13 (1H, s), 7,38-of 7.60 (4H, m), 7,95-8,08 (2H, m), 8,35 (1H, s), 8,49 (1H, s), 8,73 (1H, C)

ESI-MS (me): 504[M+H]

Example 433:

4-(1-Methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 432.

1H NMR (DMSO-d6) δ: of 1.13 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 3,50 (3H, s), 6,24 (1H, t, J=6.8 Hz), 6,46 (1H, s), 7,05 (1H, users), 7,32-7,40 (1H, m), 7,58 (1H, DD, J=8,8, 2,5 Hz), 7,74 (1H, DD, J=6,8, 2.0 Hz), 8,01 (1H, d, J=8.6 Hz), to 8.57 (1H, d, J=2.5 Hz), 8,79 (1H, d, J=2.2 Hz), 8,82 (1H, DD, J=2.5 and 1.5 Hz), for 9.47 (1H, d, J=1.4 Hz)

ESI-MS (m/e): 505[M+H]

Example 434:

4-(2-Cyano-pyridine-3-yloxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of 5-(4-methanesulfonyl-phenoxy)-2-nitro-3-(1-oxy-pyridine-3-yloxy)phenylamine:

Specified in the header of the connection will receive the same manner as in example 67 (stage 1) (stage 2), or in accordance with the method or by combining with an ordinary method but using 1-oxy-pyridine-3-ol and 6-methanesulfonyl-pyridine-3-ol.

(Stage 2) Obtain 5-(4-methanesulfonyl-phenoxy)-2-nitro-3-(2-cyano-pyridine-3-yloxy)phenylamine:

Specified in the header connection get the same pic is BOM, as in example 218 (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-(4-methanesulfonyl-phenoxy)-2-nitro-3-(1-oxy-pyridine-3-yloxy)phenylamine.

(Stage 3) to Obtain 4-(2-cyano-pyridine-3-yloxy)-6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the header of the connection receives the same way as in examples 196 (stage 5) and 204 (stage 1), or in accordance with the method or by combining with an ordinary method but using 5-(4-methanesulfonyl-phenoxy)-2-nitro-3-(2-cyano-pyridine-3-yloxy)phenylamine.

1H NMR (CD3OD) δ: 3,23 (3H, s), 7,07 (1H, users), 7,44 (1H, users), 7,56-of 7.69 (4H, m), 8,02 (1H, t, J=7.8 Hz), of 8.09 (1H, d, J=8.6 Hz), 8,29 (1H, d, J=7.8 Hz), 8,46-8,48 (1H, m), 8,55-to 8.57 (1H, m), 8,78-8,80 (1H, m)

ESI-MS (m/e): 485[M+H]

Example 435:

4-(2-Cyano-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 434, or in accordance with the method or by combining with an ordinary method but using 4-econsultancy-phenol.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7,3 Hz), up 3.22 (2H, square, J=7,3 Hz)6,94 (1H, users), 7,27 (2H, d, J=8.6 Hz), 7,33 (1H, users), 7,49 (2H, d, J=8.6 Hz), to 7.59 to 7.62 (1H, m), to $ 7.91-7,98 (3H, m), 8,24 (1H, d, J=8.6 Hz), 8,45 (1H, d, J=5,1 Hz), a total of 8.74 (1H, d, J=5,5 Hz)

ESI-MS (m/e): 498[M+H]

Example 436:

4-Benzyloxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-Ben is imidazol

Specified in the header of the connection will receive the same manner as in example 274, or in accordance with the method or by combining with an ordinary method, but using benzyl alcohol and 6-econsultancy-pyridine-3-ol accordingly.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7,6 Hz), of 3.45 (2H, square, J=7,6 Hz), 5,41 (2H, s), 7,02-7,05 (1H, m), 7,15-7,17 (1H, m), 7,39 was 7.45 (3H, m), 7,53-to 7.59 (4H, m), 8,07 (1H, d, J=8.6 Hz), 8,11-to 8.14 (1H, m), 8,39 (1H, d, J=7,0 Hz), 8,53 (1H, d, J=2.7 Hz), 8,87-of 8.90 (1H, m)

ESI-MS (m/e): 487[M+H]

Example 437:

4-Benzyloxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 205, or in accordance with the method or by combining with an ordinary method but using 3-benzyl-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 436.

1H NMR (CD3OD) δ: of 1.27 (3H, t, J=7.4 Hz), 3,42 (2H, square, J=7,4 Hz), 5,38 (2H, s), to 6.80 (1H, d, J=2.0 Hz), 7,06 (1H, d, J=2.0 Hz), of 7.36-7,42 (3H, m), 7,49 (1H, DD, J=8,8, 2,9 Hz), 7,54 (2H, d, J=6,7 Hz), 8,03 (1H, d, J=8,8 Hz), 8,49 (1H, d, J=2.7 Hz), 8,72 (1H, d, J=2.7 Hz), 8,78-8,80 (1H, m), 9,54-of 9.56 (1H, m)

ESI-MS (m/e): 488[M+H]

Example 438:

4-(2-Cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of 4-hydroxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the header of the connection receives the same way as in point is the iMER 251 (stage 1), or in accordance with the method or by combining with an ordinary method but using 4-benzyloxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 436.

(Stage 2) Obtaining 4-(2-cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the header of the connection will receive the same manner as in example 251 (stage 2), or in accordance with the method or by combining with an ordinary method but using 4-hydroxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole and 2,3-difterential.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), is 6.61 (1H, d, J=2.0 Hz), 7,28 (1H, d, J=2.0 Hz), of 7.36-7,42 (1H, m), of 7.48-rate of 7.54 (1H, m), 7,58-7,63 (2H, m), 7,65-of 7.69 (1H, m), 8,07 (2H, d, J=8,2 Hz), scored 8.38 (1H, d, J=7.8 Hz), 8,51 (1H, d, J=2.7 Hz), 8,82 (1H, d, J=4,7 Hz)

ESI-MS (m/e): 516[M+H]

Example 439:

4-(6-Cyano-pyridine-2-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 438 (stage 2), or in accordance with the method or by combining with an ordinary method but using 4-hydroxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 438 (stage 1), and 2-chloro-3-cyanopyridine.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), 3,42 (2H, square, J=7,4 Hz), 7,21 (1H, d, J=2.0 Hz), 7,30 (1H, DD, J=7,4, 5,1 is C), of 7.48 (1H, d, J=2.0 Hz), 7,58 (1H, DD, J=5,1, 7,8 Hz), 7,71 (1H, DD, J=8,8, 2,9 Hz), 8,00-with 8.05 (1H, m), 8,11 (1H, d, J=8.6 Hz), compared to 8.26-8,33 (3H, m), at 8.60 (1H, d, J=2.7 Hz), 8,78 (1H, d, J=5,1 Hz)

ESI-MS (m/e): 499[M+H]

Example 440:

4-(2-Cyano-3-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 439, or in accordance with the method or by combining with an ordinary method, but using 2,6-difterential.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz)6,91 (1H, d, J=8.6 Hz),? 7.04 baby mortality (1H, d, J=1,8 Hz), 7,13 (1H, t, J=8.6 Hz), 7,44 (1H, d, J=1,8 Hz), 7,55-to 7.64 (2H, m), to 7.67 (1H, DD, J=8,6, 3,2 Hz), 8,00-of 8.06 (1H, m), 8,10 (1H, d, J=8.6 Hz), with 8.33 (1H, d, J=7.8 Hz), to 8.57 (1H, d, J=2.3 Hz), 8,78-8,81 (1H, m)

ESI-MS (m/e): 516[M+H]

Example 441:

4-(2-Carbarnoyl-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 438.

1H NMR (CD3OD) δ: of 1.24 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 6,53 (1H, users), 7,26 (1H, users), 7,42-7,53 (2H, m), EUR 7.57 to 7.62 (2H, m), 7,68 (1H, DD, J=8,2, 3,9 Hz), 8,07 (1H, d, J=8.6 Hz), 8,11-8,16 (1H, m), to 8.41 (1H, d, J=8,2 Hz), 8,49 (1H, d, J=2.7 Hz), 8,88 (1H, d, J=3,9 Hz)

ESI-MS (m/e): 534[M+H]

Example 442:

4-(2-Cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 438, or in accordance with the method or by combining with an ordinary method but using 4-benzyloxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole obtained in example 437.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), to 6.57 (1H, users), of 7.23 (1H, users), 7,46-7,51 (1H, m), EUR 7.57-to 7.61 (1H, m), of 7.64-7,71 (2H, m), of 8.06 (1H, d, J=9.0 Hz), 8,51 (1H, d, J=2.3 Hz), 8,71 (1H, d, J=2.3 Hz), 8,78 (1H, s), 9,48 (1H, s)

ESI-MS (m/e): 517[M+H]

Example 443:

4-(2-Cyano-5-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 438 (stage 2), or in accordance with the method or by combining with an ordinary method but using 4-hydroxy-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole obtained in example 442, and 2,4-debtor-benzonitrile.

1H NMR (CD3OD) δ: of 1.20 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz), to 6.88 (1H, d, J=10,2 Hz), 6,98 (1H, d, J=2.0 Hz), 7,05-7,11 (1H, m), 7,39-7,44 (1H, m), 7,68 (1H, DD, J=3.1 and 8.0 Hz), 7,89 (1H, DD, J=8,8, 6,1 Hz), 8,08-to 8.12 (1H, m), 8,57 at 8.60 (1H, m), 8,71 (1H, d, J=2.3 Hz), 8,77-8,79 (1H, m), 9,46-9,48 (1H, m)

ESI-MS (m/e): 517[M+H]

Example 444:

4-(2-Cyano-4-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-Benz is midazol

Specified in the header of the connection will receive the same manner as in example 443, or in accordance with the method or by combining with an ordinary method, but using 2,5-debtor-benzonitrile.

1H NMR (CD3OD) δ: of 1.26 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz), for 6.81 (1H, d, J=2.3 Hz), 7,22 (1H, DD, J=4,6, and 9.0 Hz), 7,35 (1H, d, J=2.3 Hz), was 7.45 (1H, DDD, J=8,6, 4,6, 7,4 Hz), 7,63-of 7.69 (2H, m), 7,72 to 7.75 (1H, m), of 8.09 (1H, d, J=8.6 Hz), 8,55 (1H, d, J=3.1 Hz), 8,72 (1H, d, J=2.3 Hz), 8,79 (1H, DD, J=2.0 a, 3.1 Hz), 9,49 (1H, d, J=2.0 Hz)

ESI-MS (m/e): 517[M+H]

Example 445:

4-(2-Carbarnoyl-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole obtained in example 442.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), to 6.39 (1H, s), 7,21 (1H, s), 7,42-7,51 (2H, m), 7,55 (1H, DD, J=8,6, 2.7 Hz), to 7.64 (1H, d, J=7,4 Hz), of 8.06 (1H, d, J=8.6 Hz), of 8.47 (1H, d, J=2.7 Hz), 8,75-8,78 (1H, m), 8,82-8,84 (1H, m), 9,54 (1H, users)

ESI-MS (m/e): 535[M+H]

Example 446:

4-(6-Cyano-pyridine-2-yloxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 443, or in accordance with the method or by combining with the usual way, but with what ispolzovaniem 2-chloro-3-cyanopyridine.

1H NMR (CD3OD) δ: of 1.25 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz), 7,14 (1H, d, J=2.0 Hz), 7,30 (1H, DD, J=7,4, 5,1 Hz), was 7.45 (1H, d, J=2.0 Hz), 7,69 (1H, DD, J=9,0, 2.7 Hz), 8,10 (1H, d, J=9.0 Hz), 8,27-of 8.33 (2H,, m), 8,59 (1H, d, J=2.7 Hz), 8,70-8,72 (1H, m), 8,76-8,79 (1H, m), 9,41-9,43 (1H, m)

ESI-MS (m/e): 500[M+H]

Example 447:

4-(2-Cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 438, or in accordance with the method or by combining with an ordinary method but using 6-methanesulfonyl-pyridine-3-ol.

1H NMR (CD3OD) δ: 3,23 (3H, s), 6,50 (1H, s), 7,22 (1H, s), 7,45 to 7.62 (3H, m), 7,62 for 7.78 (2H, m), 7.95 is-with 8.05 (1H, m), 8,08 (1H, d, J=8,8 Hz), of 8.37 (1H, d, J=8.0 Hz), 8,49 (1H, s), 8,77 (1H, s)

ESI-MS (m/e): 502[M+H]

Example 448:

4-(2-Fluoro-6-methanesulfonyl-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 438 (stage 2), or in accordance with the method or by combining with an ordinary method but using 4-hydroxy-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 447, and 2,3-debtor-methysulfonylmethane.

1H NMR (CD3OD) δ: is 3.21 (3H, s), of 3.46 (3H, s), is 6.54 (1H, d, J=2.0 Hz), 7,27 (1H, d, J=2.0 Hz), 7,54-to 7.67 (3H, m), 7,707,74 (1H, m), to 7.93 (1H, d, J=7.8 Hz), of 8.04 (1H, d, J=8.6 Hz), 8,11 (1H, DDD, J=7,8, or 8.6, 2.7 Hz), 8,40 (1H, d, J=7.8 Hz), 8,46 (1H, d, J=2.7 Hz), 8,86 (1H, d, J=5,1 Hz)

ESI-MS (m/e): 555[M+H]

Example 449:

4-(2-Carbarnoyl-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 43 or in accordance with the method or by combining with an ordinary method but using 4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 447.

1H NMR (CD3OD) δ: 3,22 (3H, s), 6,53 (1H, d, J=1.6 Hz), 7,25 (1H, d, J=1.6 Hz), 7,42-7,53 (2H, m), EUR 7.57 (1H, DD, J=8,6, 2.7 Hz), to 7.61 (1H, d, J=7,4 Hz), to 7.68 (1H, DD, J=7,6, a 4.3 Hz), of 8.06 (1H, d, J=9.0 Hz), 8,10-8,16 (1H, m), to 8.41 (1H, d, J=8,2 Hz), of 8.47 (1H, d, J=2.7 Hz), 8,87 (1H, d, J=4.3 Hz)

ESI-MS (m/e): 520[M+H]

Example 450:

4-(2-Cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same manner as in example 442, or in accordance with the method or by combining with an ordinary method but using 6-methanesulfonyl-pyridine-3-ol.

1H NMR (CD3OD) δ: 3,23 (3H, s), to 6.57 (1H, users), of 7.23 (1H, users), 7,49 (1H, TD, J=8,0, 4.6 Hz), to 7.59 (1H, DD, J=9,0, 3.2 Hz), 7,65-7,71 (2H, m), 8,07 (1H, d, J=9,0 Hz)and 8.50 (1H, d, J=2.3 Hz), 8,71 (1H, d, J=2.3 Hz), 8,78 (1H, users), 9,48 (1H, users)

ESI-MS (m/e): 503[M+H]

Example 451:

4-(Pyridine-2-ylsulphonyl)-6-(6-ethanal who were radioactive-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solids in a light brown colour in the same way as in example 288, or in accordance with the method or by combining with an ordinary method but using 6-econsultancy-pyridine-3-ol.

1H NMR (CDCl3) δ: of 1.31 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 7,03 (1H, d, J=8.0 Hz), was 7.08 (1H, DDD, J=7,4, 4,7, 1.0 Hz), 7,35 (1H, d, J=2.2 Hz), 7,38-7,44 (2H, m), 7,52 (1H, TD, J=7,8, 2.0 Hz), to 7.64 (1H, d, J=2.1 Hz), 7,88 (1H, TD, J=7,8, 1.8 Hz), 8,03 (1H, d, J=8,8 Hz), scored 8.38 (1H, d, J=7.8 Hz), to 8.45 (1H, DD, J=4,9, 1.0 Hz), 8,53 (1H, d, J=2.7 Hz), 8,64 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 490 [M+H]

Example 452:

4-(Pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same manner as in example 68, or in accordance with the method or by combining with an ordinary method but using 3-(pyridine-2-ylsulphonyl)-5-(6-econsultancy-pyridine-3-yloxy)benzene-1,2-diamine obtained in example 451.

1H NMR (CDCl3) δ: of 1.32 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 7,08-7,19 (2H, m), 7,38 (1H, d, J=2.2 Hz), the 7.43 (1H, DD, J=8,6, 2,8 Hz), EUR 7.57 (1H, TD, J=7,8, 1.8 Hz), 7,66 (1H, d, J=2.2 Hz), of 8.04 (1H, d, J=8,6 Hz), 8,48 (1H, d, J=4,7 Hz), 8,53 (1H, d, J=2.7 Hz), 8,63 (1H, t, J=2.0 Hz), 8,69 (1H, d, J=2.5 Hz), 9,63 (1H, d, J=1.4 Hz)

ESI-MS (m/e): 491[M+H]

Example 453:

4-(1-Methyl-1H-imidazol-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzoni the azole

Specified in the header of the connection get in a solid yellow color in the same way as in example 452, or in accordance with the method or by combining with an ordinary method but using 1-methyl-1H-imidazole-2-thiol.

1H NMR (CDCl3) δ: of 1.33 (3H, t, J=7.4 Hz), to 3.41 (2H, square, J=7,4 Hz), of 3.94 (3H, s), 6,65-6,69 (1H, m), 6,77 (1H, d, J=1.4 Hz), 6.87 in (1H, d, J=1.6 Hz), 7.23 percent (1H, d, J=2.4 Hz), of 7.48 (1H, DD, J=8,6, 2,8 Hz), 7,72 (1H, d, J=2.2 Hz), with 8.05 (1H, DD, J=8,6, 0.6 Hz), 8,16 (1H, d, J=2.6 Hz), 8,54 (1H, DD, J=2,8, 0.6 Hz), 9,42 (1H, d, J=1,6 Hz)

ESI-MS (m/e): 494[M+H]

Example 454:

4-(4-Methoxybenzyl-sulfanyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid brown color in the same way as in example 452, or in accordance with the method or by combining with an ordinary method, but using (4-methoxyphenyl)methanethiol.

1H NMR (CDCl3) δ: of 1.32 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 3,61 and 3,79 (total 3H, each s), 4,05 and 4,40 (total 2H, each s), 6.69 and 6,79 (total 2H, each d, J=8.6 Hz), 6,88-7,52 (5H, m), 7,98 and 8,01 (total 1H, each d, J=8.6 Hz), 8,44 and 8,46 (total 1H, each d, J=2,9 Hz), 8,58-8,65 (1H, m), 8,68 and to 8.70 (total 1H, each d, J=2.5 Hz), 9,58 and 9,74 (total 1H, each d, J=1.4 Hz), of 10.05 and 10,46 (total 1H, each users)

ESI-MS (m/e): 534[M+H]

Example 455:

4-(6-Cyano-pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specify the OU in the title compound obtained as solid light yellow color in the same way, as in the example 446, or in accordance with the method or by combining with an ordinary method but using 2-chloro-3-cyanopyridine.

1H NMR (CDCl3) δ: of 1.32 (3H, t, J=7.4 Hz), 3,39 (2H, square, J=7,4 Hz), 7,20 (1H, DD, J=7,8, and 4.9 Hz), 7,41 (1H, d, J=2.2 Hz), was 7.45 (1H, DD, J=8,8, 2,8 Hz), 7,72 (1H, d, J=2.2 Hz), to 7.93 (1H, DD, J=7,8, 1.8 Hz), of 8.04 (1H, d, J=8.6 Hz), 8,44 (1H, DD, J=4,9, 2.0 Hz), 8,54 (1H, d, J=2,8 Hz), to 8.62 (1H, DD, J=2.5 and 1.5 Hz), to 8.70 (1H, d, J=2.5 Hz), for 9.64 (1H, d, J=1.5 Hz)

ESI-MS (m/e): 516[M+H]

Example 456:

4-(2-Cyano-pyridine-3-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 438 (stage 2), or in accordance with the method or by combining with an ordinary method but using 4-mercapto-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole obtained in example 455, and 2-cyano-3-herperidin.

1H NMR (DMSO-d6) δ: of 1.13 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 7,22 (1H, s), 7,41 (1H, s), to 7.64 (2H, DD, J=8,6, 2.7 Hz), of 7.96-of 8.04 (2H, m), 8,59-8,66 (2H, m), 8,77-8,83 (2H, m), to 9.32 (1H, s)

ESI-MS (m/e): 516[M+H]

Example 457:

4-(Pyridine-2-ylsulphonyl)-5-chloro-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same manner as in example 117 and example 290, or in accordance with the method, or what EDINENIE with in the usual way, but using pyridine-2-thiol.

1H NMR (CDCl3) δ: of 1.31 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 7,02 (1H, d, J=7.5 Hz), 7,05-7,10 (1H, m), 7,31 (1H, DD, J=8,6, 2.7 Hz), 7,41 (1H, t, J=6.0 Hz), 7,53 (1H, t, J=7.4 Hz), of 7.75 (1H, s), 7,88 (1H, t, J=7.8 Hz), 8,03 (1H, d, J=8,8 Hz), of 8.37 (1H, d, J=8.0 Hz), to 8.41 (1H, d, J=4,1 Hz)and 8.50 (1H, d, J=2.5 Hz), 8,63 (1H, s)

ESI-MS (m/e): 524, 526[M+H]

Examples 458-1, 458-2:

4-(Pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole and 4-(pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

50 mg of Oxone and 0.5 ml of water are added to a solution in methanol (3 ml), 20 mg of 4-(pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 451, and the reaction liquid was stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure and the obtained residue was diluted with ethyl acetate, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid]. Aqueous saturated solution of sodium bicarbonate is added to the obtained fractions, extracted with ethyl acetate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced giving the situation, getting listed at the beginning of the connection.

4-(Pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

1H NMR (CDCl3) δ: of 1.33 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 7,35 (1H, DD, J=8,8, 2.7 Hz), 7,37 was 7.45 (2H, m), 7,55 (1H, d, J=2.1 Hz), to 7.61 (1H, d, J=2.1 Hz), 7,89 (1H, t, J=7.8 Hz), of 7.96 (1H, t, J=7,8 Hz), 8,02 (1H, d, J=8.6 Hz), 8,15 (1H, d, J=8,2 Hz), of 8.37 (1H, d, J=7.8 Hz), 8,49 (1H, d, J=2.7 Hz), 8,65 (1H, d, J=3,7 Hz), 8,76 (1H, d, J=4.5 Hz)

ESI-MS (m/e): 506[M+H]

4-(Pyridine-2-ylsulphonyl)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole

1H NMR (CDCl3) δ: of 1.33 (3H, t, J=7.4 Hz), 3,40 (2H, square, J=7,4 Hz), 7,37 (1H, DD, J=8,6, 2,8 Hz), 7,44-7,49 (1H, m), 7,55 (1H, DD, J=7,4, and 4.5 Hz), of 7.70 (1H, d, J=1,8 Hz), 7,80 (1H, d, J=2.2 Hz), 7,88-7,94 (1H, m), of 7.96-8,02 (1H, m), of 8.04 (1H, d, J=8.6 Hz), compared to 8.26 (1H, d, J=7,4 Hz), 8,40 (1H, d, J=8.0 Hz), 8,49 (1H, d, J=2.7 Hz), 8,73 (1H, d, J=4,7 Hz), 8,77 (1H, d, J=4,9 Hz)

ESI-MS (m/e): 522[M+H]

Example 459:

6-(1-Acetylpyrrolidine-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 2'-forbiden-4-ol.

1H NMR (CDCl3) δ: 1,00-2,60 (7H, m), 3,40-4,00 (2H, m), 5,20-the 5.65 (1H, m), 7,00-7,70 (1 1H, m), 7,80-8,00 (1H, m), 8,25-to 8.45 (1H, m), 8,50-to 8.70 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 460:

6-(1-Il-2-yl)-5-(4-(deformity)phenoxy)-2-pyridin-2-yl-1H-benzimida the evils of Monteforte

(Stage 1) preparation of 4-(6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzimidazole-5-yl)oxy)benzaldehyde:

143 mg of cesium carbonate and 0,048 ml p-forventelige added to a solution of N-methyl-2-pyrrolidinone (1 ml) 100 mg 1-(2-(6-hydroxy-2-pyridin-2-yl-3-(2-trimethylsilyl-ethoxymethyl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained in example 121 (stage 11), and the reaction liquid was stirred while heating at 80°C for 3 hours. The reaction liquid is cooled to room temperature and aqueous saturated solution of ammonium chloride added thereto and extracted with ethyl acetate, the organic layer was washed with a saturated solution of salt. After drying, the solvent is evaporated and the residue purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/1)to give specified in the title compound in the form of oily substances orange color.

(Stage 2) Obtain 6-(1-acetylpyrrolidine-2-yl)-5-(4-(deformity)phenoxy)-2-pyridin-2-yl-1H-benzimidazole:

0.036 ml TRIFLUORIDE bis(2-methoxyethyl)uminosity added to a solution in chloroform (0.2 ml) 22 mg of 4-(6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzimidazole-5-yloxy)of benzaldehyde and the reaction liquid was stirred while heating at 80°C for 8 hours. The solvent volume is more under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), hexane/ethyl acetate=1/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 3) Receive monotropaceae 6-(1-acetylpyrrolidine-2-yl)-5-(4-(deformity)phenoxy)-2-pyridin-2-yl-1H-benzimidazole:

0.5 ml triperoxonane acid is added to 12 mg of 6-(1-acetylpyrrolidine-2-yl)-5-(4-(deformity)phenoxy)-2-pyridin-2-yl-1H-benzimidazole and the reaction liquid was stirred at room temperature for 1 hour. Triperoxonane acid is evaporated under reduced pressure and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid] and the solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily material red color.

1H NMR (CD3OD) δ: 0,78-of 0.95 (4H, m), 1,91-of 2.15 (2H, m), 2,69 (3H, s), 5,38-5,43 (1H, m), 7,21-7,34 (4H, m), 7,52-7,63 (6H, m), 8,27-8,29 (1H, m)

ESI-MS (m/e): 449 [M+H]

Example 461:

1-(2-(6-(3-Chloro-4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 3-chloro-4-methanol who were radioactive)phenol.

1H NMR (CDCl3) δ: 1,85-to 2.40 (4H, m), 2,90-3,27 (5H, m), 3,65-are 3.90 (2H, m), 5,15-5,43 (1H, m), 6.90 to was 7.45 (5H, m), 7,84-of 8.15 (2H, m), 8,35-8,42 (1H, m), 8,60-8,68 (1H, m)

ESI-MS (m/e): 511[M+H]

Example 462:

2-(6-(1-Acetylpyrrolidine-2-yl)-5-(4-(methanesulfonyl)phenoxy)-1H-benzimidazole-2-yl)(1,3)thiazolo(5,4-b)pyridine monotropaceae

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 306 (stage 4) (stage 5), or in accordance with the method or by combining with an ordinary method, but using tert-butyl 2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)phenyl)pyrrolidin-1-carboxylate obtained in example 306 (stage 3), and (1,3)thiazolo(5,4-b)pyridine-2-carboxylic acid.

1H NMR (CD3OD) δ: 1,60-to 2.40 (7H, m), 3.00 and-of 3.80 (5H, m), 5,00-the ceiling of 5.60 (1H, m), 7,20-7,40 (2H, m), 7,25-7,80 (3H, m), of 7.90-8,10 (2H, m), 8,40-8,80 (2H, m)

ESI-MS (m/e): 534[M+H]

Example 463:

5-(1-acetylpyrrolidine-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-(5-(trifluoromethyl)pyridin-2-yl)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 462, or in accordance with the method or by combining with an ordinary method but using 5-(trifluoromethyl)pyridine-2-carboxylic acid.

1H NMR (CDCl3) δ: 0,89 (1H, m), 1,22 (2H, m), 1,88-2,11 (3H, m), and 2.27 (1H, m), is 3.08 (3H, m), 3,63 is 3.76 (1H, m), 3,84 (1H, s)5,38 (1H, DD, J=25,8, 8.6 Hz), 7,11-7,20 (2H, m), 7,39 (1H, m), 7,54 (1 is, m), to 7.93 (2H, m), 8,11 (1H, m), 8,51 (1H, m), 8,93 (1H, m), of 10.58-10,88 (1H, m)

ESI-MS (m/e): 545[M+H]

Example 464:

6-(1-Acetylpyrrolidine-2-yl)-2-(5-(deformity)pyridine-2-yl)-5-(4-methanesulfonyl)phenoxy)-1H-benzimidazole monotropaceae

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 462, or in accordance with the method or by combining with an ordinary method but using 5-(deformity)pyridine-2-carboxylic acid.

1H NMR (CD3OD) δ: 0,92 (1H, m), 1,32 (2H, m), 1,89 (1H, m), 1,97-of 2.08 (2H, m), 2.13 and with 2.14 (1H, m), 2,69 (3H, s), 3,16-3,17 (3H, s), to 5.35 (1H, m), 7,30-to 7.32 (1H, m), 7,41-7,58 (1H, m), 7,60 to 7.62 (1H, m), 8,00-8,02 (3H, m), 8,04 is 8.22 (2H, m), 9,04 (1H, m)

ESI-MS (m/e): 527[M+H]

Example 465:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(methoxymethyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole monotropaceae

7 mg of sodium borohydride are added to a solution in methanol (0.5 ml) 50 mg of 4-(6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzimidazole-5-yloxy)benzaldehyde obtained in example 460 (stage 1), while cooling with ice and the reaction liquid is stirred for 1 hour. Aqueous saturated solution of ammonium chloride is added to the reaction liquid, and extracted it with ethyl acetate. The organic layer was washed with saturated salt solution, dried with anhydrous sodium sulfate and the solvent is evaporated under reduced pressure, the learn the crude product.

10 mg of sodium hydride and 0,030 ml under the conditions added to the solution in dimethylformamide (1 ml) of the obtained crude product and stirred at room temperature for 30 minutes. Aqueous saturated solution of ammonium chloride is added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous sodium sulfate, the solvent is evaporated under reduced pressure to give crude product. 0.5 ml triperoxonane acids are added to the obtained crude product, and the reaction liquid was stirred at room temperature for 2 hours. Triperoxonane acid is evaporated under reduced pressure and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid] and the solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily yellow substance.

1H NMR (CD3OD) δ: of 1.93 (1H, m), 2,07-2,11 (3H, m)to 2.18 (2H, m), of 2.45 (1H, m), 3.43 points (3H, d, J=3.1 Hz), 3.75 to of 3.95 (2H, m), 4,50 (d, 2H, J=4.3 Hz), 5,49-to 5.56 (1H, m), 7,16 (3H, m), 7,44-7,49 (2H, m), EUR 7.57 (1H, m,), 7,70-7,73 (1H, m), 8,15 (1H, m), 8,27-8,30 (1H, m), 8,89 (1H, m)

ESI-MS (m/e): 443 [M+H]

Example 466:

1-(4-(6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)ethanol is antipsoriatic

0.4 ml of methyl lithium (a 1.0 M solution in diethyl simple ether) is added at -78°C to a solution in tetrahydrofuran (1.3 ml) of 70 mg of 4-(6-(1-(acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1-(2-(trimethylsilyl)ethoxy)methyl)-1H-benzimidazole-5-yloxy)benzaldehyde obtained in example 460 (stage 1), and the reaction liquid was stirred at -78°C within 30 minutes. A saturated solution of ammonium chloride is added to the reaction liquid, and extracted it with ethyl acetate. The organic layer was washed with saturated salt solution, dried with anhydrous sodium sulfate and the solvent is evaporated under reduced pressure to give crude product. 0.5 ml triperoxonane acids are added to the obtained crude product and stirred at room temperature for 90 minutes and then triperoxonane acid is evaporated and the residue purified liquid chromatography with reversed phase with an average pressure [ODS-AS-360-CC (YMC), mobile phase: water-acetonitrile-0.1% of triperoxonane acid], the solvent of the resulting fraction is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily yellow substance.

1H NMR (CD3OD) δ: 0,90-to 0.96 (1H, m)is 1.31 (4H, m), 1,25-1,90 (3H, m), 2,42 (1H, m), 2,68 (3H, s), 3,89-3,91 (1H, m), of 5.50 (1H, m), 7,02-7,33 (4H, m), 7,42-7,52 (2H, m), to 7.59-to 7.67 (1H, m), 8,10-to 8.14 (1H, m), by 8.22-compared to 8.26 (1H, m), 8,80-8,87 (1H, m)

ESI-MS (m/e): 443[M+H]

Example 467:

6-(1-Acetimer is lidin-2-yl)-5-(4-(3-methyl-[1,2,4]-oxadiazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily dark brown material in the same manner as in example 122 or in accordance with the method or by combining with an ordinary method but using 5-(4-itfinal)-3-methyl-[1,2,4]-oxadiazole.

1H NMR (CDCl3) δ: 1,39-2,49 (10H, m), 3,42-3,88 (2H, m), 5,14 of 5.4 (1H, m), 6,70-8,96 (10H, m)

ESI-MS (m/e): 481[M+H]

Example 468:

(1-Acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-yl acetate, diastereoisomer A

(Stage 1) preparation of 3-((tert-butyl(dimethyl)silyl)oxy) dihydrofuran-2(3H)-it:

9.0 g of imidazole and 15.9 g of tert-butyldimethylsilyl chloride are added to a solution in dimethylformamide (180 ml) 9.0 g of 3-hydroxydehydrogenase-2-(3H)-she and the reaction liquid is stirred for 1 hour at room temperature. The reaction liquid was diluted with ethyl acetate, washed with water and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=5/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 2) Obtaining N-(4-(2-((tert-butyl(dimethyl)silyl) oxy)-4-hydroxybutanoic)-3-forfinal)pyridine-2-carboxamide:

3,1 ml of n-butyl lithium (2,66 M solution in hexane) was added ka the NML to the solution in tetrahydrofuran (100 ml), 1.1 g of N-(4-bromo-3-forfinal)pyridine-2-carboxamide at -78° C and the reaction liquid was stirred at the same temperature for 15 minutes. to 1.21 g of 3-((tert-butyl(dimethyl)silyl)oxy)dihydrofuran-2(3H)-it is added to the reaction liquid and the reaction liquid was stirred at the same temperature for 1 hour. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid at the same temperature, then warmed to room temperature and extracted with ethyl acetate. The organic layer is dried with anhydrous sodium sulfate, the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 3) Obtaining N-(4-(2-((tert-butyl(dimethyl)silyl) oxy)-1,4-dihydroxybutyl)-3-forfinal)pyridine-2-carboxamide:

114 mg of sodium borohydride are added to a solution in methanol (20 ml) 860 mg of N-(4-(2-((tert-butyl(dimethyl)silyl)oxy)-4-hydroxybutanoic)-3-forfinal)pyridine-2-carboxamide under ice cooling and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with her chloroform and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under decreased the pressure and the obtained residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/1), getting listed in the title compound in the form of a solid white color.

(Stage 4) to Obtain N-(4-(3-((tert-butyl(dimethyl) silyl)oxy)pyrrolidin-2-yl)-3-forfinal)pyridine-2-carboxamide:

155 mg of triethylamine and 130 mg methanesulfonyl chloride are added to a solution in chloroform (8 ml) 165 mg of N-(4-(2-((tert-butyl(dimethyl)silyl)oxy)-1,4-dihydroxybutyl)-3-forfinal)pyridine-2-carboxamide under ice cooling and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 25 mg of sodium azide are added to a solution in dimethylformamide (5 ml) of the obtained residue, and the reaction liquid was stirred at 40°C for 2 hours. The reaction liquid is cooled, add it to water, extracted with ethyl acetate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 50 mg sodium borohydride and 5 mg of pentahydrate copper sulfate add accordingly to a solution in methanol (10 ml) of the obtained residue, and the reaction liquid was stirred at 40°C for 2 hours. The reaction liquid is cooled, add it to the water saturated solution of sodium bicarbonate, extragear the jut of her with chloroform, and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 5) to Obtain 1-acetyl-2-(2-fluoro-4-((pyridin-2-ylcarbonyl)amino)phenyl)pyrrolidin-3-yl acetate:

2 ml of 4n hydrochloric acid in dioxane are added to a solution in methanol (1 ml) of 59 mg of N-(4-(3-((tert-butyl(dimethyl)silyl)oxy)pyrrolidin-2-yl)-3-forfinal)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and 100 mg of triethylamine, 90 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine add accordingly to the solution in chloroform (5 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 15 minutes. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=200/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 6) to Obtain 1-acetyl-2-(2-fluoro-5-nitro-4-((pyridin-2-ylcarbonyl)amino)phenyl)pyrrolidin-3-yl acetate, diastereoisomer A and diastereoisomer B:

1 ml of fuming what she nitric acid is added to 57 mg of N-(4-(3-((tert-butyl(dimethyl)silyl)oxy)pyrrolidin-2-yl)-3-forfinal)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 40 minutes. The reaction liquid was poured into a mixed with ice water saturated solution of sodium bicarbonate, extracted with chloroform and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1)to give diastereoisomer diastereoisomer a and B indicated in the title compound, each in the form of an oily yellow substance.

(Stage 7) Obtaining the diastereoisomer A 1-acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-yl acetate:

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(methanesulfonyl)phenol and diastereoisomer A 1-acetyl-2-(2-fluoro-5-nitro-4-((pyridin-2-ylcarbonyl)amino)phenyl)pyrrolidin-3-yl acetate.

1H NMR (CDCl3) δ: 1,86-2,42 (8H, m), 3.04 from-3,10 (3H, m), 3.72 points-was 4.02 (2H, m), 5,06 is 5.38 (2H, m), 7,08-of 7.70 (5H, m), 7,83-of 7.97 (3H, m), 8.34 per-8,42 (1H, m), 8,61-8,68 (1H, m), 10,54-10,65 (1H, m)

ESI-MS (m/e): 535[M+H]

Example 469:

1-Acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-ol, diastereoisomer A

5 mg of potassium carbonate are added to a solution in methanol (2 ml) 14 mg of diastereoisomer A (1-a shall ethyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-yl acetate, obtained in example 468, and the reaction liquid was stirred overnight at room temperature. The solvent is evaporated and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,82-2,47 (5H, m), 3.05, and is 3.08 (3H, s), 3,70-of 3.97 (2H, m), 4,29 is 4.45 (1H, m), 5,00-5,32 (1H, m), 7,00-to 7.67 (5H, m), 7,81-of 7.96 (2H, m), 8,00-8,42 (1H, m), 8,60-8,69 (1H, m), to 10.62-10,85 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 470:

6-(1-Acetyl-4,5-dihydro-1H-pyrrol-2-yl)-5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

2 mg TRIFLUORIDE bis(2-methoxyethyl)uminosity added to a solution in chloroform (1 ml), 2 mg of diastereoisomer A of 1-acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-ol obtained in example 469, and the reaction liquid was stirred at room temperature for 15 minutes. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)to give specified in the title compound as a colorless oily substance.

1H NMR (CDCl3) δ: 1,40-4,43 (10H, m), 7.03 is-7,80 (6H, m), 7,82-of 7.95 (3H, m), 8,32-8,46 (1H, m), 8,60-8,71 (1H, m), 10,38-or 10.60 (1H, m)

ESI-MS (m/e): 475[M+H]

Example 471:

1-Acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-yl acetate, diastereoisomer B

Specified in the header of the connection will receive the same manner as in example 468 (stage 7), or in accordance with the method or by combining with an ordinary method but using diastereoisomer B (1-acetyl-2-(2-fluoro-5-nitro-4-((pyridin-2-ylcarbonyl)amino)phenyl)pyrrolidin-3-yl acetate obtained in example 468 (stage 6).

1H NMR (CDCl3) δ: 1,72-of 2.30 (8H, m), 3,02-is 3.08 (3H, m), 3,64-3,99 (2H, m), 5,26-vs. 5.47 (1H, m), 5,58-5,72 (1H, m), 7,09-7,73 (5H, m), 7,82-7,94 (3H, m), 8,33-8,43 (1H, m), 8,60-to 8.70 (1H, m), 10,47-is 10.68 (1H, m)

ESI-MS (m/e): 535[M+H]

Example 472:

1-Acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-ol, diastereoisomer B

Specified in the header of the connection will receive the same manner as in example 469, or in accordance with the method or by combining with an ordinary method but using diastereoisomer B (1-acetyl-2-(5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-3-yl acetate obtained in example 471.

1H NMR (CDCl3) δ: 1,78-of 2.25 (5H, m), 3,03-3,10 (3H, m), 3,60-4,00 (2H, m), 4,50-and 4.68 (1H, m), 5,27-of 5.45 (1H, m), 7.03 is-7,73 (5H, m), 7,81-of 7.96 (3H, m), 8,32-to 8.45 (1H, m), 8,60-8,69 (1H, m), 10,51-was 10.82 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 473:

1-(4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)piperidine-2-he

Specified in the header with the Association obtained as an oily substance in the same way, as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1-(4-hydroxyphenyl)piperidine-2-it.

1HN1H NMR (CDCl3) δ: 1,74-2,62 (13H, m), 3,52-a 3.87 (4H, m), 5,18 and 5.36 (1H, m), of 6.71-to 7.64 (7H, m), 7,76 - of 7.90 (1H, m), compared to 8.26-to 8.41 (1H, m), 8,56-8,68 (1H, m), 10,98-11,33 (1H, m)

ESI-MS (m/e): 496[M+H]

Example 474:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-vinylpyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-vinylpyridin-3-ol.

1H NMR (CDCl3) δ: 1,40-of 2.50 (7H, m), 3,40-4,00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6.90 to-8,00 (11H, m), 8,20-to 8.45 (1H, m), 8,50-to 8.70 (2H, m), or 10.60-10,90 (1H, m)

ESI-MS (m/e): 476[M+H]

Example 475:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(2-forfinal)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(2-forfinal)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 3.45 points-of 4.00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-8,05 (10H, m), 8,30-to 8.45 (1H, m), 8,50-to 8.70 (2H, m), 10,80-11,20 (1H, m)

ESI-MS (m/e): 494[M+H]

Example 476:

1-(2-(6-(3-Fluoro-4-methanesulfonyl-phenoxy)-2-PI is one-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using (3-fluoro-4-methanesulfonyl)phenol.

1H NMR (CDCl3) δ: 1,87-of 2.38 (4H, m), 2,85-3,27 (5H, m), 3,60-of 3.95 (2H, m), 5,20-5,41 (1H, m), 6,83-7,00 (1H, m), 7,28-7,40 (4H, m), 7,81-7,98 (2H, m), 8,35-8,42 (1H, m), 8,60-8,68 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 477:

1-(4-{[6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-pyridin-2-yl-1H-benzimidazole-5-yl]oxy}phenyl)pyrrolidin-2-he

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1-(4-hydroxyphenyl)pyrrolidin-2-it.

1H NMR (CDCl3) δ: 1,80-to 2.40 (6H, m), 2,62 (2H, m), 3,55-of 3.95 (4H+1/2H, m), 5,28 (1/2H, m), 6.90 to-7,10 (3H, m), 7,35 (1N+1/2H, m), 7,45-the 7.65 (2H+1/2H, m), a 7.85 (1H, m), a 8.34 (1H, m), 8,61 (1H, m), 10,4-to 10.8 (1H, user.)

ESI-MS (m/e): 482[M+H]

Example 478:

1-(4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)pyridin-2(1H)-he

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1-(4-hydroxyphenyl)pyridine-2(1H)-it.

1H NMR (CDCl 3) δ: 1,72-2,42 (7H, m), 3,48-3,86 (2H, m), 5,15-5,52 (1H, m), is 6.19-6,32 (1H, m), 6,61-of 6.73 (1H, m), 6,80-7,66 (9H, m), to 7.77-7,89 (1H, m), 8,32-to 8.41 (1H, m), charged 8.52-8,65 (1H, m), 11,07 of $ 11.48 (1H, m)

ESI-MS (m/e): 492[M+H]

Example 479:

5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-2,2'-bipyridine monotropaceae

Specified in the title compound obtained as a yellow substance in the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 2,2'-bipyridine-5-ol.

1H NMR (CD3OD) δ: 1,80 is 2.80 (7H, m), 3,60-of 4.05 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 7,50-of 7.90 (4H, m), 8,00-of 8.15 (1H, m), 8,15-of 8.25 (1H, m), 8,30-to 8.40 (1H, m), 8,45 at 8.60 (1H, m), 8,60-9,00 (5H, m)

ESI-MS (m/e): 477[M+H]

Example 480:

N-(2-(2-(6-(4-Methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)methanesulfonamide

Specified in the header of the connection will receive the same manner as in example 171 and 178, or in accordance with the method or by combining with an ordinary method but using 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 162 (step 7), and N-tert-butoxycarbonyl-glycine.

1H NMR (CD3OD) δ: 1,93-and 2.14 (3H, m), 2.06 to of 2.27 (1H, m), 2,86 and 2.95 (total 3H, each s)of 3.13 (3H, s), 3,43-4,08 (4H, m), 5,20 is 5.38 (1H, m), 7,20-of 7.60 (5H, m), 7,93-8,02 (3H, m), 8,23-8,30 (1H, m), a total of 8.74 (1H, users)

ESI-MS (m/e): 570[M+H]

Example 481:

Ethyl (2-(2-(6-(4-methanesulfonyl-phenoxy)-2-p is ridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)carbamate

Specified in the header of the connection will receive the same manner as in example 171 and 181, or in accordance with the method or by combining with an ordinary method but using 5-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 162 (step 7), and N-tert-butoxycarbonyl-glycine.

1H NMR (CD3OD) δ: and 1,18 1,23 (total 3H, each t, J=each of 7.1 Hz), 1.93 and with 2.14 (3H, m), 2,22 is 2.44 (1H, m), 3,12 3,13 and (total 3H, each s), 3,30-4,13 (6H, m), 5,24-5,33 (1H, m), 7,20-of 7.60 (5H, m), 7,93 shed 8.01 (3H, m), of 8.28 (1H, t, J=8,2 Hz), 8,73 (1H, users)

ESI-MS (m/e): 564[M+H]

Example 482:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-bromophenoxy)-2-pyridin-2-yl-1H-benzimidazole enantiomer A

(Stage 1) to Obtain enantiomer A and enantiomer B of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide:

100 mg of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 338 (stage 4), separated using a column for separating optical isomers (CHIRAL CEL OD 2 cmϕx 25 L (Daicel Chemical), mobile phase: hexane/ethanol/diethylamine=60/40/0,1, flow rate: 10 ml/min), the enantiomer A (retention time: 17,8 min) and enantiomer B (retention time: 21,0 min), each in the form of a solid of light yellow color.

(Stage 2) to Obtain enantiomer A of 6-(1-acetylpyrrolidine-2-yl)-5-(4-bromophenoxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the header Conn is get out in the form of oily substance in the same way, as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using enantiomer A of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 482 (stage 1), and 4-bromophenol.

1H NMR (CDCl3) δ: 1,56-2,41 (7H, m), 3,42-are 3.90 (2H, m), 5,16-the 5.51 (1H, m), 6,78-7,66 (7H, m), 7,80-to 7.93 (1H, m), 8,32-8,44 (1H, m), 8,54-8,67 (1H, m), 11,14-11,65 (1H, m)

ESI-MS (m/e): 479[M+H]

Example 483:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-bromophenoxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomer B

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 482 (stage 1), and 4-bromophenol.

ESI-MS(m/e): 479 [M+H]

Example 484:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 483, or in accordance with the method or by combining with an ordinary method but using 6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,51 is 2.43 (7H, m), 2,59-to 2.74 (3H, m), 3,50-3,93 (2H, m), 5,17-5,46 (1H, m), 7,00-7,72 (4H, m), 7,2-8,13 (2H, m), 8.34 per-8,44 (1H, m), 8,57-8,69 (2H, m), 10,75-11,14 (1H, m)

ESI-MS (m/e): 482[M+H]

Example 485:

5-(1-Acetyl-3-methylpyrrolidine-2-yl)-6-(4-(methylsulphonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of N-(3-fluoro-4-(2-(2-hydroxyethyl)acryloyl)phenyl)pyridine-2-carboxamide:

136 mg of 60% sodium hydride are added to a solution in tetrahydrofuran (20 ml), 1.0 g of N-(4-bromo-3-forfinal)pyridine-2-carboxamide under ice cooling and the reaction liquid was stirred at the same temperature for 15 minutes. The reaction liquid is cooled to -78°C and add to it dropwise 1,53 ml n-utility (2,66 M solution in hexane) and the reaction liquid was stirred at the same temperature for 30 minutes. 0,36 ml 3-metilendigidrazid-2(3H)-it is added to the reaction liquid at the same temperature and the reaction liquid was stirred at the same temperature for 2 hours, then heated to 0°C and stirred for 30 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid at the same temperature, extracted with ethyl acetate and the organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=3/1), is the learn specified in the title compound as a colorless oily substance.

(Stage 2) Obtaining N-(4-(1,4-dihydroxy-2-methylbutyl)-3-forfinal)pyridine-2-carboxamide:

150 mg of sodium borohydride are added to a solution in methanol (8 ml) 320 mg of N-(3-fluoro-4-(2-(2-hydroxyethyl)acryloyl)phenyl) pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 1 hour. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 3) Obtaining N-(4-(1-acetyl-3-methylpyrrolidine-2-yl)-3-forfinal)pyridine-2-carboxamide:

of 0.18 ml of triethylamine and 0.07 ml methanesulfonyl chloride are added to a solution in chloroform (5 ml) 100 mg N-(4-(1,4-dihydroxy-2-methylbutyl)-3-forfinal)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 23 mg of sodium azide are added to a solution in dimethylformamide (4 ml) polucen the th residue and the reaction liquid was stirred at 40° C for 2 hours. The reaction liquid is cooled to room temperature, add water, extracted with ethyl acetate and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 50 mg sodium borohydride and 5 mg pentahydrate of copper sulfate are added to a solution in methanol (5 ml) of the obtained residue, and the reaction liquid was stirred at 40°C for 15 minutes. The reaction liquid is cooled to room temperature and then add aqueous saturated solution of sodium bicarbonate, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 0.08 ml of triethylamine, 0,07 ml of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine added to a solution in chloroform (4 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 4) to Obtain N-(4-(1-acetyl-3-methyl who irreligion-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide:

1 ml of fuming nitric acid is added to 70 mg of N-(4-(1-acetyl-3-methylpyrrolidine-2-yl)-3-forfinal)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 2 hours. The reaction liquid was poured into a mixture of ice and aqueous saturated solution of sodium bicarbonate, extracted with chloroform and the extract is dried with anhydrous sodium carbonate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 5) to Obtain 5-(1-acetyl-3-methylpyrrolidine-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using N-(4-(1-acetyl-3-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide and 4-(methanesulfonyl)phenol.

1H NMR (CDCl3) δ: 0,81-2,73 (9H, m), 3,03-3,11 (3H, m), 3,36-3,99 (2H, m), 4,65-5,43 (1H, m), 7,00 to 7.75 (5H,), 7,81-7,79 (3H, m), 8,32-to 8.45 (1H, m), 8,60-8,68 (1H, m), 10,51-was 10.82 (1H, user)

ESI-MS (m/e): 491[M+H]

Example 486:

6-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-3,4-dihyd naftalin-1(2H)-he

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-hydroxy-3,4-dihydronaphthalene-1(2H)-it.

1H NMR (CDCl3) δ: 1,00-3,00 (13H, m), 3,40-of 3.95 (2H, m), 5,00-5,50 (1H, m), 6,60-7,80 (5H, m), 7,80-to 8.20 (2H, m), 8,30-and 8.50 (1H, m), 8,50-8,80 (1H, m), 10,80-11,20 (1H, m)

ESI-MS (m/e): 467[M+H]

Example 487:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(1H-imidazol-1-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(1H-imidazol-1-yl)phenol.

1H NMR (CDCl3) δ: 1,00-2,50 (7H, m), 3,50-4,50 (2H, m), 5,20-6,00 (1H, m), 6,80-8,80 (13H, m)

ESI-MS (m/e): 465[M+H]

Example 488:

6-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-1-methyl-[1,2,3,4]-tetrahydronaphthalen-1-ol

0,050 ml bromide Metalmania (5.0 M solution in tetrahydrofuran) is added with ice cooling to a solution in tetrahydrofuran (0.5 ml) of 7 mg of 6-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-3,4-dihydronaphthalene-1(2H)-she obtained in example 486, and the reaction liquid was stirred at 0°C for 30 minutes. The reaction liquid was diluted chlorine is formom, washed with aqueous saturated solution of ammonium chloride and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound as a colorless oily substance.

1H NMR (CDCl3) δ: 1,10-2,80 (16H, m), 3,50-4,00 (2H, m), 5,10-of 5.50 (1H, m), 6,60-of 7.90 (7H, m), 8,30-and 8.50 (1H, m), 8,50-70 (1H, m)

ESI-MS (m/e): 465[M+H]

Example 489:

6-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-[1,2,3,4]-tetrahydronaphthalen-1-ol

5 mg of sodium borohydride added under ice cooling to a solution in tetrahydrofuran (0.5 ml) of 7 mg of 6-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-3,4-dihydronaphthalene-1(2H)-she obtained in example 486, and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid was diluted with chloroform, washed with aqueous saturated solution of ammonium chloride and dried with anhydrous sodium sulfate. The solvent is evaporated and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound as a colorless oily substance.

1H NMR (CDCl3) δ: 1,00-2,50 (14H, m), 4,00-6,0 (3H, m), 6,80-8,50 (9H, m)

ESI-MS (m/e): 469[M+H]

Example 490:

5-(1-Acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole, diastereoisomer A

(Stage 1) preparation of ethyl (2Z)-4-((tert-butyl(dimethyl)silyl)oxy)-2-verboten-2-oat:

Solution in tetrahydrofuran (40 ml) 2.0 g ethyl (diethoxyphosphoryl)(fluoro)acetate is cooled at -78°C and then to it is added dropwise 3.4 ml of n-butyl lithium (2,66 M solution in hexane) and the reaction liquid was stirred at the same temperature for 15 minutes. of 2.1 ml ((tert-butyl)dimethyl)siliconvalley added to the reaction liquid and the reaction liquid was stirred at the same temperature for 2 hours. At the same temperature aqueous saturated solution of sodium bicarbonate is added to the reaction liquid and heated to room temperature, then extracted with ethyl acetate. It is dried with anhydrous sodium sulfate, the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=50/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 2) Obtaining N-(4-((2Z)-4-((tert-butyl(dimethyl)silyl)oxy)-2-verboten-2-IMT-3-forfinal)pyridine-2-carboxamide:

136 mg of 60% sodium hydride are added to a solution in tetrahydrofuran (40 ml) 1,0g N-(4-bromo-3-forfinal)pyridine-2-carboxamide under ice cooling and the reaction liquid was stirred at the same temperature for 20 minutes. The reaction liquid is cooled to -78°C, add to it dropwise 1,53 ml of n-butyl lithium (2,66 M solution in hexane) and the reaction liquid was stirred at the same temperature for 20 minutes. At the same temperature 1.07 g of ethyl (2Z)-4-((tert-butyl(dimethyl)silyl)oxy)-2-verboten-2-oate added to the reaction liquid and the reaction liquid was stirred at the same temperature for 4 hours. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid at the same temperature, warmed to room temperature and extracted with ethyl acetate. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=3/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 3) N-(4-(4-((tert-butyl(dimethyl)silyl)oxy)-2-fluoro-1-hydroxybutyl)-3-forfinal)pyridine-2-carboxamide:

100 mg of the catalyst 10% palladium on coal are added to a solution in methanol (20 ml), 300 mg of N-(4-((2Z)-4-((tert-butyl(dimethyl)silyl)oxy)-2-verboten-2-IMT-3-forfinal)pyridine-2-carboxamide and in hydrogen atmosphere, the reaction liquid was stirred at room temperature for 4 hours the century The catalyst was removed by filtration, the solvent is evaporated under reduced pressure and 50 mg of sodium borohydride are added to a solution in methanol (4 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 1 hour. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with ethyl acetate and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=100/1), getting mentioned in the title compound as a colorless oily substance.

(Stage 4) to Obtain N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-3-forfinal)pyridine-2-carboxamide, diastereoisomer A, and the diastereoisomer B:

46 mg of triethylamine and 39 mg methanesulfonyl chloride are added to a solution in chloroform (5 ml) 100 mg N-(4-(4-((tert-butyl(dimethyl)silyl)oxy)-2-fluoro-1-hydroxybutyl)-3-forfinal)pyridine-2-carboxamide, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with chloroform and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 22 mg of sodium azide are added to a solution in dimethylformamide (4 ml) poluchennogo the residue and the reaction liquid was stirred at 40° C for 2 hours. The reaction liquid is cooled, add it to water, extracted with ethyl acetate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and 0.3 ml of tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) are added to a solution in tetrahydrofuran (4 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 1 hour. Water added to the reaction liquid, extracted with ethyl acetate and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, and 46 mg of triethylamine and 39 mg methanesulfonyl chloride are added to a solution in chloroform (5 ml) of the obtained residue, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated solution of sodium bicarbonate is added to the reaction liquid, extracted with ethyl acetate and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and a solution in methanol (4 ml) of the obtained residue, add 10 mg of the pentahydrate of copper sulfate and 50 mg of sodium borohydride and the reaction liquid was stirred at 40°C for 1 hour. The reaction liquid is cooled, add it to the water saturated solution of sodium bicarbonate, extracted with chloroform and dried with anhydrous sodium sulfate. Dissolve the al is evaporated under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine added to a solution in chloroform (4 ml) of the obtained residue, the reaction liquid was stirred at room temperature for 30 minutes. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (chloroform/methanol=30/1)to give diastereoisomer diastereoisomer a and B indicated in the title compound, each in the form of a colorless oily substance.

(Stage 5) to Obtain 5-(1-acetyll-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole, a diastereoisomer A:

0.5 ml of fuming nitric acid is added to 18 mg of diastereoisomer A of N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-3-forfinal)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 10 minutes. The reaction liquid was poured into a mixture of ice and aqueous saturated solution of sodium bicarbonate, extracted with chloroform, and then the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product. Specified in the title compound obtained as solid light yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using the obtained crude product is KTA and 4-(methanesulfonyl)phenol.

1H NMR (CDCl3) δ: 1,85-to 2.40 (5H, m), 3,06 and to 3.09 (3H, s), 3,79-4,08 (2H, m), 4,96-5,62 (2H, m), 7,05-of 7.70 (5H, m), 7,83-to 7.99 (3H, m), 8.34 per-8,43 (1H, m), 8,61-8,69 (1H, m), of 10.58-10,84 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 491:

6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-5-(4-(2-thienyl)phenoxy)-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(2-thienyl)phenol.

1H NMR (CDCl3) δ: 1,05-of 2.45 (7H, m), 3,40-4,00 (2H, m), 5,10-the ceiling of 5.60 (1H, m), 6,80-8,00 (1 1H, m), 8,30-and 8.50 (1H, m), 8,50-8,80 (1H, m)

ESI-MS (m/e): 481[M+H]

Example 492:

2-(4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1H-isoindole-1,3(2H)-dione

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 2-(4-hydroxyphenyl)-1H-isoindole-1,3-(2H)-dione.

1H NMR (CDCl3) δ: 1,05-to 2.40 (7H, m), 3,40-of 4.05 (2H, m), of 5.05-the ceiling of 5.60 (1H, m), 6,80-8,20 (12H, m), 8,30-to 8.70 (2H, m)

ESI-MS (m/e): 544[M+H]

Example 493:

5-(1-Acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl) phenoxy)-2-pyridin-2-yl-1H-benzimidazole, diastereoisomer B

Specified in the title compound obtained as solid light yellow color in the same way is, as in the example 490 (stage 5), or in accordance with the method or by combining with an ordinary method but using diastereoisomer B N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-3-forfinal)pyridine-2-carboxamide, obtained in example 490 (stage 4).

1H NMR (CDCl3) δ: 1,80-of 2.45 (5H, m), 3.05, and is 3.08 (3H, s), 3,61-or 4.31 (2H, m), 5.08 to 5,54 (2H, m), 7.03 is-7,80 (5H, m), 7,81-of 7.97 (3H, m), 8,33-8,43 (1H, m), 8,60-8,68 (1H, m), 10,52-of 10.75 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 494:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(5-methyl-1H-tetrazol-1-yl)phenol.

1H NMR (CD3OD) δ: 1,91 and 2.15 (total 3H, each s), 1,97-of 2.20 (3H, m), 2,22-of 2.58 (1H, m), 2.63 in and 2.64 (total 3H, each s), 3,62-4,00 (2H, m), 5,34-5,42 (1H, m), 7,22-to 7.68 (7H, m), 7,94-with 8.05 (1H, m), 8,30 (1H, t, J=7.8 Hz), 8,76 (1H, users)

ESI-MS (m/e): 481[M+H]

Example 495:

Ethyl 5-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridine-2-carboxylate

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using ethyl 5-hydroxypyridine-2-carboxylate.

p> 1H NMR (CDCl3) δ: 1,30-1,50 (3H, m), 1,50-2,50 (7H, m), 3,50-are 3.90 (2H, m), 4,35-4,60 (2H, m), 5,10-of 5.45 (1H, m), 6.90 to-of 7.70 (4H, m), 7,80-of 7.95 (1H, m), 8,00-to 8.20 (1H, m), 8.30 to-8,80 (3H, m), or 10.60-11,20 (1H, m)

ESI-MS (m/e): 472[M+H]

Example 496:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-pyrazin-2-elfenix)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-pyrazin-2-kilfenora.

1H NMR (CDCl3) δ: 0,80-to 2.40 (7H, m), 3,60-are 3.90 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-8,05 (8H, m), 8.30 to-8,80 (4H, m), 8,90-9,10 (1H, m), the 10.40-10,80 (1H, m)

ESI-MS (m/e): 477[M+H]

Example 497:

6-(1-Acetylpyrrolidine-2-yl)-5-(1H-indol-5-yloxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1H-indol-5-ol.

1H NMR (CDCl3) δ: 1,20-to 2.40 (7H, m), 3,60-4,00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,40-6,60 (1H, m), 6,80-of 8.00 (7H, m), 8,20-of 8.50 (2H, m), 8,50-8,80 (1H, m)

ESI-MS (m/e): 438[M+H]

Example 498:

(2-(2-(5-((2'-Forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl)methylamine

(Stage 1) Obtaining dihydrochloride (3-fluoro-4-pyrrolidin-2-ylphenyl)amine:

100 ml of a 4n solution of hydrochloric acid in dioc the ane added to a solution of 19 g of tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrolidin-1-carboxylate, obtained in example 338 (step 2), in a mixture of 50 ml of ethyl acetate and 50 ml of methanol under ice cooling and the reaction mass is stirred over night at room temperature. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

(Stage 2) Obtain 2,2,2-Cryptor-N-(3-fluoro-4-(1-(TRIFLUOROACETYL)pyrrolidin-2-yl)phenyl)ndimethylacetamide:

39 ml of pyridine and 24 ml of anhydride triperoxonane acid are added to a solution in chloroform (200 ml), 20 g of the dihydrochloride (3-fluoro-4-pyrrolidin-2-ylphenyl)amine under ice cooling and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily substance brown.

(Stage 3) Obtain 2,2,2-Cryptor-N-(5-fluoro-2-nitro-4-(1-(TRIFLUOROACETYL)pyrrolidin-2-yl)phenyl)ndimethylacetamide:

100 ml of fuming nitric acid is added to 28 g of 2,2,2-Cryptor-N-(3-fluoro-4-(1-(TRIFLUOROACETYL)pyrrolidin-2-yl)phenyl)ndimethylacetamide under ice cooling and the reaction liquid was stirred at room temperature for 1 hour. Ice water is added to the reaction LM the bone, to dilute it, then extracted with ethyl acetate, washed with saturated salt solution and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=10/1), getting mentioned in the title compound as an oily yellow substance.

(Stage 4) to Obtain tert-butyl 2-(4-amino-2-fluoro-5-nitrophenyl)pyrrolidin-1-yl-of-carboxylate:

150 ml of aqueous 1N solution of sodium hydroxide are added to a solution in tetrahydrofuran (150 ml) 29 g of 2,2,2-Cryptor-N-(5-fluoro-2-nitro-4-(1-(TRIFLUOROACETYL)pyrrolidin-2-yl)phenyl)ndimethylacetamide under ice cooling and the reaction liquid was stirred at room temperature for 5 hours. 23 ml of di-tert-butyl dicarbonate added to the reaction liquid and the reaction liquid is stirred for 30 minutes. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=5/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 5) Obtaining t is et-butyl 2-(4-amino-2-((2'-forbiden-4-yl)oxy)-5-nitrophenyl)pyrrolidin-1-carboxylate:

200 mg of 2'-forbiden-4-ol and 184 mg of potassium carbonate are added to a solution in N,N-dimethylformamide (3 ml) 288 mg of tert-butyl 2-(4-amino-2-fluoro-5-nitrophenyl)pyrrolidin-1-carboxylate and the reaction liquid was stirred overnight at 80°C. the Reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=5/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 6) to Obtain tert-butyl 2-(4,5-diamino-2-((2'-forbiden-4-yl)oxy)phenyl)pyrrolidin-1-carboxylate:

1 ml of Raney Nickel with a developed surface are added to a solution in methanol (5 ml) 410 mg of tert-butyl 2-(4-amino-2-((2'-forbiden-4-yl)oxy)-5-nitrophenyl)pyrrolidin-1-carboxylate and the reaction liquid is stirred in hydrogen atmosphere at room temperature for 1 day. The catalyst was removed by filtration through Celite, the solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1), getting mentioned in the title compound as an oily substance brown.

(Stage 7) to Obtain 5-((2 forbiden-4-yl)oxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole:

1.6 ml of N-((1E)pyridine-2-ylmethylene)aniline (1 M solution in methanol) are added to a solution in methanol (5 ml) 255 mg of tert-butyl 2-(4,5-diamino-2-((2'-forbiden-4-yl)oxy)phenyl) pyrrolidin-1-carboxylate and the reaction liquid was stirred at 90°C for 1 day. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and 332 mg of the obtained residue add 5 ml of 4n hydrochloric acid in dioxane and the reaction liquid was stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure, diluted with saturated aqueous sodium hydrogen carbonate and extracted with chloroform. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol/aqueous ammonia=20/1/0,1), getting mentioned in the title compound in the form of a substance light yellow color.

(Stage 8) Getting (2-(2-(5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl)methylamine:

19 mg of N-(tert-butoxycarbonyl)-N-methylglycine 24 mg monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (1 ml), 37 mg of 5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole and the reaction liquid was stirred at room temperature for 3 hours. 2 ml of 4n hydrochloric acid in dioxane is added to the reaction liquid and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with chloroform and alkalinized adding thereto aqueous saturated solution of sodium carbonate and the organic layer was washed with saturated salt solution and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CDCl3) δ: 1,60-2,60 (6H, m), 2,80 was 3.05 (1H, m), 3,10-4,00 (4H, m), 5,20-the ceiling of 5.60 (1H, m), 6,95-7,70 (11N, m), 7,75-of 7.95 (1H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m)

ESI-MS (m/e): 522[M+H]

Example 499:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,3,4]-oxadiazol-2-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily yellow substance in the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(5-methyl-[1,3,4]-oxadiazol-2-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,40-to 2.40 (7H, m), 2,50 is 2.80 (3H, m), 3,50-of 3.95 (2H, m), of 5.05-of 5.50 (1H, m), 6,80-7,80 (4H, m), 7,80-8,00 (1H, m), 8,05 to 8.3 (1H, m), 8,30-and 8.50 (1H, m), 8,50-8,80 (2H, m), 10,50-11,00 (1H, m)

ESI-MS (m/e): 482[M+H]

Example 500:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-([1,3,4]oxadiazol-2-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily yellow substance in the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-([1,3,4]-oxadiazol-2-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,40-to 2.40 (7H, m), 3,50-of 3.95 (2H, m), of 5.05-of 5.50 (1H, m), 6,80-7,80 (4H, m), 7,80-8,00 (1H, m), 8,05-8,80 (5H, m), 10,50-11,00 (1H, m)

ESI-MS (m/e): 468[M+H]

Example 501:

6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-5-(4-(pyrimidine-2-elfenix)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-pyrimidine-2-kilfenora.

1H NMR (CD3OD) δ: 1,90 and 2.13 (total 3H, each s), 1,94 of $ 2.53 (4H, m), 3,62-of 3.80 (1H, m), 3,80-4,00 (1H, m), 5,38-5,46 (1H, m), 7,16-7,56 (6H, m), 7,95-of 8.04 (1H, m), 8,24-of 8.33 (1H, m), 8,46 (2H, d, J=9.0 Hz), 8,70-8,79 (1H, m,), 8,83 cent to 8.85 (2H, m)

ESI-MS (m/e): 477[M+H]

Example 502:

1-((5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridin-2-yl)methyl)pyrrolidin-2,5-dione

Specified in the title compound obtained as a solid substance of white color in the same way the m as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1-((5-hydroxypyridine-2-yl)methyl)pyrrolidin-2,5-dione.

1H NMR (CDCl3) δ: 1,80-2,46 (7H, m), 2,74-of 2.86 (4H, m), 3,53-are 3.90 (2H, m), 4,76-to 4.87 (2H, m), 5,18-of 5.48 (1H, m), 6,76-to 7.67 (5H, m), 7,80-to $ 7.91 (1H, m), 8,28-8,44 (2H, m), 8,57-8,67 (1H, m), 11,07-11,41 (1H, m)

ESI-MS (m/e): 511[M+H]

Example 503:

6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-5-((6-(5-(trifluoromethyl)-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(5-(trifluoromethyl)-[1,2,4]-oxadiazol-3-yl)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,89-2,54 (7H, m), 3,84-4,01 (2H, m), 5,32-5,42 (1H, m), 7,20-7,80 (4H, m), 7,98-8,03 (1H, m), 8,24-of 8.37 (2H, m), 8,60-8,65 (1H, m), 8,73-8,80 (1H, m)

ESI-MS (m/e): 536[M+H]

Example 504:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-chloropyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-chloropyridin-3-ol.

1H NMR (CDCl3) δ: 1,60-2,60 (7H, m), 3,50-of 3.95 (2H, m), 5,10-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (5H, m), 7,80-of 8.50 (3H, m), 8,50-to 8.70 (1H, m), or 10.60-11,00 (N, m)

ESI-MS (m/e): 434[M+H]

Example 505:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-bromopyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-bromopyridin-3-ol.

1H NMR (CDCl3) δ: 1,60-2,60 (7H, m), 3,50-of 3.95 (2H, m), 5,10-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (5H, m), 7,70-8,00 (1H, m), 8,05-of 8.50 (2H, m), 8,50-to 8.70 (1H, m), or 10.60-11,00 (1H, m)

ESI-MS (m/e): 478, 480[M+H]

Example 506:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-methoxypyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in a solid yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-methoxypyridine-3-ol.

1H NMR (CDCl3) δ: 1,60-2,60 (7H, m), 3,50-4,10 (5H, m), 5,10-5,70 (1H, m), 6,60-of 7.70 (5H, m), 7,70-of 7.95 (1H, m), 7,95-8,10 (1H, m), 8,25-to 8.45 (1H, m), 8,50-to 8.70 (1H, m), or 10.60-11,00 (1H, m)

ESI-MS (m/e): 430[M+H]

Example 507:

5-((2'-Forbiden-4-yl)oxy)-6-(1-(methanesulfonyl) pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a colorless oily substance in the same manner as in example 178, or in accordance with the method or by combining with the usual way, but with use the of 5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole, obtained in example 498 (stage 7).

1H NMR (CDCl3) δ: 1,80-2,20 (3H, m), 2,20-of 2.50 (1H, m), 2.70 height is 3.00 (3H, m), 3,40-of 3.80 (2H, m), 5,10-of 5.40 (1H, m), 6.90 to-8,10 (12H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 529[M+H]

Example 508:

Methyl 2-(5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxylate

Specified in the title compound obtained as a colorless oily substance in the same manner as in example 181, or in accordance with the method or by combining with an ordinary method but using 5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 498 (stage 7).

1H NMR (CDCl3) δ: 1,80-2,20 (3H, m), 2,20-of 2.50 (1H, m), 3,40-of 3.80 (5H, m), 5,10-of 5.40 (1H, m), 6.90 to-8,10 (12H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 509[M+H]

Example 509:

2-(5-((2'-Forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)-N,N-dimethylpiperidin-1-carboxamid

Specified in the title compound obtained as a solid substance of white color in the same way as in example 336 (stage 1) (stage 2), or in accordance with the method or by combining with an ordinary method but using 5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 498 (stage 7).

1H NMR (CDCl3) δ: 1,60-of 2.20 (3H, m), 2,20-of 2.50 (1H, m), of 2.72 (3H, s)2,84 (3H, s), 3,40-of 3.80 (2H, m), 5,10-of 5.40 (1H, m), 6.90 to-8,10 12H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 522[M+H]

Example 510:

1-((5-(6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridine-2-ylmethyl)pyrrolidin-2-he

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1-((5-hydroxypyridine-2-yl)methyl)pyrrolidin-2-it.

1H NMR (CDCl3) δ: 1,80-to 2.57 (11N, m), 3.33 and-the 3.89 (4H, m), 4,48 with 4.64 (2H, m), 5,20-5,5l (1H, m), 6,77-to 7.67 (5H, m), to 7.77-of 7.90 (1H, m), 8,27-8,42 (2H, m), 8,56-8,66 (1H, m), 11,16-11,53 (1H, m)

ESI-MS (m/e): 497[M+H]

Example 511:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(3-methyl-1H-[1,2,4]-triazole-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(3-methyl-1H-[1,2,4]-triazole-5-yl)phenol.

1H NMR (CDCl3) δ: 1,76-2,82 (10H, m), 3,50-are 3.90 (2H, m), 5,13-5,59 (1H, m), 6,64-8,04 (8H, m), 8,23-8,64 (2H, m)

ESI-MS (m/e): 480[M+H]

Example 512:

6-(1-(Divercity)pyrrolidin-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 498 (stage 8), or in accordance with the method, is whether the Association with in the usual way, but using diflorasone acid.

1H NMR (CDCl3) δ: 1,80-of 2.50 (4H, m), 3,60-4,20 (2H, m), 5,20-of 6.20 (2H, m), 6.90 to-8,10 (12H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 529[M+H]

Example 513:

2-(2-(5-((2'-Forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoacetate

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 498 (stage 8), or in accordance with the method or by combining with an ordinary method but using acetoxidans acid.

1H NMR (CDCl3) δ: 1,60-to 2.40 (7H, m), 3,40-4,00 (2H, m), 4,05-4,80 (2H, m), 5,10-the ceiling of 5.60 (1H, m), 6.90 to-8,10 (12H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 551[M+H]

Example 514:

(5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridin-2-yl)methanol

20 mg of the mixed hydride of lithium and aluminium added under ice cooling to a solution in tetrahydrofuran (2 ml) 90 mg of ethyl 5-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridine-2-carboxylate obtained in example 495, and the reaction liquid was stirred at 0°C for 30 minutes. The reaction liquid was diluted with chloroform, washed with aqueous saturated solution of ammonium chloride, aqueous saturated solution of sodium bicarbonate and a saturated solution of salt accordingly and dried by besttranslator sodium. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,60-2,60 (7H, m), 3,50-4,00 (2H, m), 4,70-4,85 (2H, m), 5,10-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (5H, m), 7,70-of 7.95 (1H, m), 8,30-of 8.50 (2H, m), 8,50-to 8.70 (1H, m)

ESI-MS (m/e): 430[M+H]

Example 515:

2-(2-(5-((2'-Forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl-2-oxoethyl

10 mg of potassium carbonate are added to a solution in methanol (0.5 ml) 11 mg of 2-(2-(5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl acetate obtained in example 513, and the reaction liquid was stirred at room temperature for 1 day. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,40-of 2.50 (4H, m), 3,40-4,20 (4H, m), of 5.05-5,70 (1H, m), 6.90 to-8,10 (12H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (/e): 509[M+H]

Example 516:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(permitil)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

0,050 ml trichloride bis(2-methoxyethyl)uminosity added to a solution in chloroform (1 ml) 17 mg (5-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridin-2-yl)methanol obtained in example 514, while cooling with ice and the reaction liquid was stirred at 0°C for 2 hours. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium hydrogen carbonate and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid of light yellow color.

1H NMR (CDCl3) δ: 1,60-2,60 (7H, m), 3,50-4,00 (2H, m), of 5.05-the ceiling of 5.60 (3H, m), 6,80-of 7.70 (5H, m), 7,70-of 7.95 (1H, m), 8,30-of 8.50 (2H, m), 8,50-to 8.70 (1H, m), or 10.60-11,00 (1H, m)

ESI-MS (m/e): 432[M+H]

Example 517:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(3-methyl-[1,2,4]-oxadiazol-5-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(3-methyl[1,2,4]-oxadiazol-5-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,65-2.57 m (10H, m), 3,48-3,93 (5H, m), 5,17-5,52 (1H, m), 6,82-to 7.67 (7H, m), 7,80-to $ 7.91 (1H, m), 8.34 per-8,44 (1H, m), 8,57-8,67 (1H, m), 11,32-11,68 (1H, m)

ESI-MS (m/e): 482[M+H]

Example 518:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(1-methyl-1H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(1-methyl-1H-tetrazol-5-yl)phenol.

1H NMR (CDCl3) δ: 1,83-to 2.40 (7H, m), to 3.58-are 3.90 (2H, m), is 4.15 and 4.19 (total 3H, each s), 5,16-of 5.48 (1H, m), 6,93 for 7.78 (7H, m), 7,80-to $ 7.91 (1H, m), 8.34 per-8,42 (1H, m), 8,56-8,65 (1H, m)

ESI-MS (m/e): 481[M+H]

Example 519:

6-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy-N-methylpyridin-2-carboxamide

Specified in the title compound obtained as solid light yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 5-hydroxy-N-methylpyridin-2-carboxamide.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 2,90-3,10 (3H, m), 3,50-4,00 (2H, m), of 5.05-of 5.50 (1H, m), 6,80-of 7.70 (3H, m), 7,70-of 8.00 (2H, m), 8,10-of 8.50 (3H, m), 8,50-to 8.70 (1H, m)

ESI-MS (m/e): 457[M+H]

Example 520:

3-(5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridin-2-yl)-1,3-oxazolidin-2-he

Specified in reception the e connection receive in the form of a solid of light yellow color in the same way, as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 3-(5-hydroxypyridine-2-yl)-1,3-oxazolidin-2-it.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 3,50-4,00 (2H, m), 4,10-of 4.35 (2H, m), 4,40-4,60 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (4H, m), 7,70-8,00 (1H, m), 8,10-of 8.50 (3H, m), 8,50-to 8.70 (1H, m), 10,70-11,10 (1H, m)

ESI-MS (m/e): 485[M+H]

Example 521:

6-(1-Acetylpyrrolidine-2-yl)-5-(6-methylpyridin-3-ylsulphonyl)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-methylpyridin-3-thiol.

1H NMR (CDCl3) δ: 1,20-2,50 (10H, m), 3,50-4,00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-8,00 (6H, m), 8,20-to 8.70 (3H, m)

ESI-MS (m/e): 430[M+H]

Example 522:

Methyl 5-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)nicotinate

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using methyl 5-hydroxynicotinate.

1H NMR (CD3OD) δ: 1,89 and 2.14 (total 3H, each s), 1,96-of 2.20 (3H, m), 2,32-of 2.54 (1H, m), 3,63-are 3.90 (2H, m), 3,93 (3H, s), lower than the 5.37-5,41 (1H, m), 7,20-EUR 7.57 (3H, m), 7,92-8,03 (2H, m), 8,30 (1H, t, J=8,4 Hz), 8,65-8,67 (1H, m), a total of 8.74-8,78 (1H, m), 8,89-of 8.92 (1H, m)/p>

ESI-MS (m/e): 458[M+H]

Example 523:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-methylthio)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-methylthiopyridine-3-ol.

1H NMR (CDCl3) δ: 1,60-2,70 (10H, m), 3,50-4,00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-8,10 (6H, m), 8,20-of 8.50 (2H, m), 8,50-to 8.70 (1H, m), 10,70-11,10 (1H, m)

ESI-MS (m/e): 446[M+H]

Example 524:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(1,3-dimethyl-1H-[1,2,4]-triazole-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(1,3-dimethyl-1H-[1,2,4]-triazole-5-yl)phenol.

1H NMR (CDCl3) δ: 1,79-2,53 (10H, m), 3,50-3,90 (5H, m), 5,19-and 5.30 (1H, m), 6.87 in-7,66 (5H, m), to 7.77-to $ 7.91 (1H, m), of 7.96-8,10 (2H, m), 8,33-8,43 (1H, m), 8,56-8,67 (1H, m), 10,82-11,08 (1H, m)

ESI-MS (m/e): 494[M+H]

Example 525:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(1,5-dimethyl-1H-[1,2,4]-triazole-3-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with conventional methods for the Ohm, but using 4-(1,5-dimethyl-1H-[1,2,4]-triazole-3-yl)phenol.

1H NMR (CDCl3) δ: 1,79-2,53 (10H, m), 3,50-3,90 (5H, m), 5,19-and 5.30 (1H, m), 6.87 in-7,66 (5H, m), to 7.77-to $ 7.91 (1H, m), of 7.96-8,10 (2H, m), 8,33-8,43 (1H, m), 8,56-8,67 (1H, m), 10,82-11,08 (1H, m)

ESI-MS (m/e): 494[M+H]

Example 526:

6-(1-Acetylpyrrolidine-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 3)-(stage 5), or in accordance with the method or by combining with an ordinary method, but using tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrolidin-1-carboxylate obtained in example 338 (step 2), and pyrazin-2-carboxylic acid and 2'-forbiden-4-ol.

1H NMR (CDCl3) δ: 1,20-2,50 (7H, m), 3,50-of 3.95 (2H, m), 5,10-the ceiling of 5.60 (1H, m), 6,80-7,80 (10H, m), 8,50-of 8.90 (2H, m), 9,40-10,00 (1H, m), 10,50-11,20 (1H, m)

ESI-MS (m/e): 494[M+H]

Example 527:

6-(1-Acetylpyrrolidine-2-yl)-5-((5-chloropyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 5-chloro-3-pyridinol.

1H NMR (CD3OD) δ: 1,89 and 2.15 (total 3H, each s), 1,94-of 2.20 (3H, m), 2,29-2,49 (1H, m), 3,62-of 3.97 (2H, m), 5,32-of 5.40 (1H, m), 7,17-7,63 (4H, m), 7,94-of 8.04 (1H, m), compared to 8.26-to 8.41 (3H, m), 8,73-8,79 (1H, m)

ESI-MS (m/e): 43[M+H]

Example 528:

1-(5-(6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridin-2-yl)pyrrolidin-2-he

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 1-(5-hydroxypyridine-2-yl)pyrrolidin-2-it.

1H NMR (CDCl3) δ: 1,79-2,43 (9H, m), 2,58-a 2.71 (2H, m), 3,53-to 3.89 (2H, m), 3,98-4,17 (2H, m), to 5.21-to 5.57 (1H, m), 6,77-EUR 7.57 (4H, m), 7,74-8,66 (5H, m)

ESI-MS (m/e): 483[M+H]

Example 529:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-methylpyridin-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 6-methylpyridin-3-ol.

1H NMR (CDCl3) δ: 1,60-2,60 (10H, m), 3,50-of 3.95 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,65-7,80 (4H, m), 8,20-to 8.40 (1H, m), 8,50-to 8.70 (2H, m), 9,50-to 9.70 (1H, m), or 10.60-11,40 (1H, m)

ESI-MS (m/e): 415[M+H]

Example 530:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-([1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-([1,2,4]-oxadiazol-3-yl)pyridin-Ola.

1H NMR (CDCl3) δ: 1,80 is 2.43 (7H, m), 3,57-to 3.92 (2H, m), 5,19-5,46 (1H, m), 6,98-8,43 (7H, m), 8,55-8,87 (3H, m), 10,53-a 10.74 (1H, m)

ESI-MS (m/e): 468[M+H]

Example 531:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(1,3-oxazol-4-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(1,3-oxazol-4-yl)phenol.

1H NMR (CD3OD) δ: 1,89-of 2.20 (6H, m), 2,28-of 2.50 (1H, m), 3,62-4,00 (2H, m), 5,39-of 5.50 (1H, m), 7,12-7,53 (5H, m), 7,80-7,89 (2H, m), 7,93-of 8.04 (1H, m), 8,24-8,33 (3H, m), 8,70-8,79 (1H, m)

ESI-MS (m/e): 466[M+H]

Example 532:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-chloropyridin-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 6-chloropyridin-3-ol.

1H NMR (CDCl3) δ: 1,60-2,60 (7H, m), 3,50-of 3.95 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,65-8,30 (5H, m), 8,40-to 8.70 (2H, m), 9,50-to 9.70 (1H, m), or 10.60-11,60 (1H, m)

ESI-MS (m/e): 435[M+H]

Example 533:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or under what about the way or Association with an ordinary method but using 4-(2-methyl-2H-tetrazol-5-yl)phenol.

1H NMR (CD3OD) δ: 1,90-2,19 (6H, m), 2,27 is 2.51 (1H, m), 3,61-4,00 (2H, m), 4,43, and of 4.44 (total 3H, each s), 5,38-5,46 (1H, m), 7.23 percent (2H, d, J=8.6 Hz), 7.24 to 7,60 (2H, m), 8,11-8,19 (2H, m), 8,67-to 8.70 (1H, m), 8,77 (1H, users), 9,46 (1H, d, J=8.6 Hz)

ESI-MS (m/e): 482[M+H]

Example 534:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-bromopyridin-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 6-bromopyridin-3-ol.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 3,60-of 3.95 (2H, m), 5,20-of 5.50 (1H, m), 6,80-8,40 (5H, m), 8,50-8,80 (2H, m), 9,50-to 9.70 (1H, m), the 10.40-11,10 (1H, m)

ESI-MS (m/e): 479, 481[M+H]

Example 535:

5-(1-Acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomer A and enantiomer B

10 mg of diastereoisomer B 5-(1-acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole obtained in example 493, share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/ethanol/diethylamine=40/60/0,1, flow rate: 10 ml/min) enantiomer A (retention time: 10,5 min) and enantiomer B (retention time: 19,0 min), each in the form of a solid substance b the logo color.

Enantiomer A:

ESI-MS(m/e): 495 [M+H]

Enantiomer B:

ESI-MS(m/e): 495 [M+H]

Example 536:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(1-methyl-1H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(1-methyl-1H-tetrazol-5-yl)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,88 and 2.02 (total 3H, each s), 1,93-of 2.20 (3H, m), 2,28-of 2.50 (1H, m), 3,60-4,00 (2H, m), 4,47, and 4,48 (total 3H, each s), 5,32-5,42 (1H, m), 7,22-of 7.70 (4H, m), 7,95-8,02 (1H, m), 8,25-8,32 (2H, m), 8,61-8,64 (1H, m), 8,73 (1H, users)

ESI-MS (m/e): 482[M+H]

Example 537:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(1-methyl-1H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 6-(1-methyl-1H-tetrazol-5-yl)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,91 and 2.16 (total 3H, each s), 2,00-of 2.20 (3H, m), 2,38 is 2.55 (1H, m), 3,63-4,01 (2H, m), 4,50 and 4.51 (total 3H, each s), 5,35-5,44 (1H, m), 7,33-of 7.60 (2H, m), 7,66-7,73 (1H, m), 8,27-to 8.34 (1H, m), 8,65-8,67 (1H, m), 8,71-8,73 (1H, m), 8,78-8,80 (1H, m), 9,48-9,50 (1H, m)

ESI-MS (m/e): 483[M+H]

Example 538:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-the l)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,91-of 2.20 (6H, m), 2,33-2,52 (1H, m), 3,60-4,00 (2H, m), 4,48-of 4.90 (3H, m), lower than the 5.37-5,44 (1H, m), 7,22-to 7.68 (4H, m), 7,97-of 8.04 (1H, m), 8,19-8,23 (1H, m), 8,25-8,31 (1H, m), 8,55-8,59 (1H, m), a total of 8.74 (1H, users)

ESI-MS (m/e): 482[M+H]

Example 539:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 4-(5-methyl-1H-tetrazol-1-yl)phenol.

1H NMR (CD3OD) δ: 1,91 and 2.16 (total 3H, each s), 1,96-of 2.20 (3H, m), 2,33-of 2.54 (1H, m), 2.63 in and 2.64 (total 3H, each s), 3,64-4,00 (2H, m), 5,38-5,43 (1H, m), 7,32-EUR 7.57 (4H, m), to 7.61-to 7.68 (2H, m), 8,70-8,73 (1H, m), 8,78-8,80 (1H, m), for 9.47-9,49 (1H, m)

ESI-MS (m/e): 482[M+H]

Example 540:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(1H-pyrazole-1-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(1H-pyrazole-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,67-2,48 (7H, m), 3,50-to 3.92 (2H, m), 5,14-to 5.57 (1H, m), 6,41-6,50 (1H, m), 6,80-8,03 (7H, m), 8.17-a 8,67 (4H, m), 11,00-11,27 (1H, m)

ESI-MS (m/e): 466[M+H]

Example 541:

6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-5-(6-(1H-[1,2,4]-triazole-1-yl)pyridine-3-yl)oxy-1H-benzimidazole

Specified in the title compound obtained as an oily substance by the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(1H-[1,2,4]-triazole-1-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,62-of 2.45 (7H, m), 3,52-are 3.90 (2H, m), 5,20-of 5.55 (1H, m), 6,79-8,68 (10H, m), 9,02-9,13 (1H, m), 11,17-to 11.52 (1H, m)

ESI-MS (m/e): 467[M+H]

Example 542:

5-(4-(2-Methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole, enantiomer A and enantiomer B

59,0 mg of 5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in the same manner as in example 162 (stage 2)-(stage 7), using 4-(2-methyl-2H-tetrazol-5-yl)phenol, share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: ethanol/2-propanol/diethylamine=25/75/0,1, flow rate: 12 to 18 ml/min) enantiomer A and enantiomer b (retention Time: enantiomer A of 13.5 min; enantiomer B 30,8 min, CHIRALPAK AD 4.6 mmϕ× 250 L (Daicel Chemical), mobile phase: ethanol/2-propanol/diethylamine=25/75/0,1, flow rate: 1 ml/is in).

Example 543:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomer A

0,006 ml of acetic anhydride are added to a solution in chloroform (1 ml) of 24.7 mg of enantiomer A 5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 542, and the reaction liquid was stirred at room temperature for 10 minutes. The reaction solvent is evaporated under reduced pressure and the resulting residue purified separation by thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), receiving one chiral form specified in the connection header in the form of a solid white color.

1H NMR (CD3OD) δ: 1,90-of 2.20 (6H, m), 2,24-2,49 (1H, m), 3,66-4,00 (2H, m), lower than the 5.37-5,46 (1H, m), 7,12-of 7.60 (5H, m), 7,94-of 8.04 (1H, m), 8,04-to 8.20 (2H, m), 8,29 (1H, t, J=8,2 Hz), 8,68-8,78 (1H, m)

ESI-MS (m/e): 481[M+H]

Example 544:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomer B

0,007 ml of acetic anhydride are added to a solution in chloroform (1 ml) 30.9 mg of enantiomer B 5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in example 542, and the reaction liquid was stirred at room temperature for 10 minutes. The reaction solvent is evaporated under reduced pressure and the obtained OST the current clean separation by thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), receiving one chiral form specified in the connection header in the form of a solid white color.

ESI-MS(m/e):481 [M+H]

Example 545:

5-(1-Acetyl-5-methylpyrrolidine-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomers A, B, C and D

A mixture of the four components specified in the connection header receive the same manner as in example 485, or in accordance with the method or by combining with an ordinary method but using 5-methyldihydro-2(3H)-she. 15 mg of the mixture of the four components separated using a column for separating optical isomers (CHIRAL-CEL OD-H 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/ethanol/diethylamine=80/20/0,1), the enantiomer A (retention time; 13,67 min)and enantiomer B (retention time: 15,24 min)and enantiomer C (retention time: 18,96 min) and enantiomer D (retention time: 22,90 min), each in the form of a solid light yellow.

Enantiomer A:

1H NMR (CDCl3) δ: 1,23-to 1.38 (3H, m), 1,50-to 2.57 (7H, m), 3.04 from and is 3.08 (3H, s), 4,24-4,60 (1H, m), 5,18-5,43 (1H, m), 6,92-7,83 (5H, m), 7,83-7,98 (3H, m), 8.34 per-8,43 (1H, m), 8,60-8,67 (1H, m), 10,84-11,33 (1H, m)

ESI-MS (m/e): 491[M+H]

Enantiomer B:

1H NMR (CDCl3) δ: 1,22-of 2.20 (9H, m), 2,23 at 2.45 (1H, m), 3.04 from and is 3.08 (3H, s), 4,10-4,22 (1H, m), 5,09-5,23 (1H, m),? 7.04 baby mortality-of 7.70 (5H, m), 7,83-of 7.97 (3H, m), 8.34 per-8,48 (1H, m), 8,61-8,69 (1H, m), of 10.73-11,16 (1H, m)

ESI-MS (m/e): 491[M+H]

Enantio the EP C:

ESI-MS(m/e): 491 [M+H]

Enantiomer D:

ESI-MS(m/e): 491 [M+H]

Example 546:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,88-of 2.20 (6H, m), 2.21 are 2,31 (1H, m), 3,61-4,00 (2H, m), 4,46, and to 4.47% (total 3H, each s), 5,34-5,44 (1H, m), 7,22-7,71 (3H, m), 8,18 is 8.25 (1H, m), 8,50 at 8.60 (1H, m), 8,65-to 8.70 (1H, m), 8,72-8,80 (1H, m), 9,44 for 9.47 (1H, m)

ESI-MS (m/e): 483[M+H]

Example 547:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(2-(methoxymethyl)-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(2-(methoxymethyl)-2H-tetrazol-5-yl)phenol.

1H NMR (CD3OD) δ: 1,90-of 2.20 (6H, m), 2,22-a 2.71 (1H, m), 3,53 (3H, s), 5,38-5,46 (1H, m), 5,96 and 5,97 (total 3H, each s), 7,20-7,56 (5H, m), 7,95-8,03 (1H, m), 8.17 and is 8.22 (2H, m), 8,29 (1H, t, J=8.0 Hz), 8,73-8,79 (1H, m)

ESI-MS (m/e): 511[M+H]

Example 548:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(methoxymethyl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection get in the de oily substance in the same way, as in example 483, or in accordance with the method or by combining with an ordinary method but using 6-(methoxymethyl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,60 is 2.43 (7H, m), 3,34-3,91 (5H, m), 4,45-4,59 (2H, m), 5,20-5,52 (1H, m), 6,86-to 7.67 (5H, m), 7,80-of 7.90 (1H, m), 8,29-8,48 (2H, m), 8,55-8,67 (1H, m), 10,87-11,27 (1H, m)

ESI-MS (m/e): 444[M+H]

Example 549:

2-(2-(5-(4-(2-Methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 168, or in accordance with the method or by combining with an ordinary method but using 5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in the same manner as in example 162 (stage 2)-(stage 7), but using 4-(2-methyl-2H-tetrazol-5-yl)phenol.

1H NMR (CD3OD) δ: 1,94-of 2.16 (3H, m), 2.23 to-2,48 (1H, m), 3,57-4,34 (4H, m), 4,43, and of 4.44 (total 3H, each s), 5,27-5,52 (1H, m), 7,17-EUR 7.57 (5H, m), 7,94-of 8.04 (1H, m), 8,09-to 8.20 (2H, m), 8,24-8,32 (1H, m), 8,69-8,81 (1H, m)

ESI-MS (m/e): 497[M+H]

Example 550:

6-(1-Acetyl-3-ftorpirimidinu-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the header of the connection will receive the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using diastereoisomer B -(4-(1-acetyl-3-ftorpirimidinu-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 493, and 6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,82-2,43 (5H, m), of 2.68 and 2.70 (3H, s), 3,64-and 4.40 (2H, m), 5,19-of 5.40 (1H, m), 5,42-5,64 (1H, m), 7,02-7,79 (4H, m), 7,80-a 7.92 (1H, m), 8,00-to 8.12 (1H, m), 8,35-8,42 (1H, m), 8,60 is 8.75 (2H, m), 10,50-is 10.68 (1H, m)

ESI-MS (m/e): 500[M+H]

Example 551:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(2-ethyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 4-(2-ethyl-2H-tetrazol-5-yl)phenol.

1H NMR (CD3OD) δ: 1,68 (3H, t, J=7.2 Hz), 1,90 and 2.13 (total 3H, each s), 1,97-of 2.20 (3H, m), 2,29 of $ 2.53 (1H, m), 3,62-4,00 (2H, m), 4,73-7,79 (2H, m), lower than the 5.37-vs. 5.47 (1H, m), 7,19-of 7.60 (5H, m), 7,93-8,03 (1H, m), 8,10-to 8.20 (2H, m,), 8,23-of 8.33 (1H, m), a total of 8.74 (1H, users)

ESI-MS (m/e): 495[M+H]

Example 552:

2-(5-(4-(2-Methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxamid

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 184, or in accordance with the method or by combining with an ordinary method but using 5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole obtained in the same manner as in example 162 (stage 2)-(stage 7), but using 4-(2-methyl-2H-tetraza the-5-yl)phenol.

1H NMR (CD3OD) δ: 1,97-2,10 (3H, m), 2,28-to 2.41 (1H, m), 3,52-3,63 (1H, m), 3,74-3,62 (1H, m), 5,26-5,41 (1H, m), 7,10-7,33 (1H, m), 7.23 percent (2H, d, J=8,8 Hz), 7,44-to 7.61 (2H, m), 7.95 is-to 7.99 (1H, m)to 8.12 (2H, d, J=8,8 Hz), of 8.27 (1H, d, J=8,2 Hz), 8,72-8,73 (1H, m)

ESI-MS (m/e): 482[M+H]

Example 553:

6-(1-Acetyl-3-ftorpirimidinu-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 550, or in accordance with the method or by combining with an ordinary method but using 4-(2-methyl-2H-tetrazol-5-yl)phenol.

1H NMR (CD3OD) δ: 1,83-2,17 (total 3H, each s), 2,10-to 2.40 (2H, m), 3,62-is 4.21 (2H, m), to 4.41 and was 4.42 (total 3H, each s), 5,23-5,43 (1H, m), 5,46-5,73 (1H, m), 7,10-the 7.65 (5H, m), 7,94-8,02 (1H, m), 8,03-8,17 (2H, m), of 8.27 (1H, t, J=8,8 Hz), 8,72 (1H, users)

ESI-MS (m/e): 499[M+H]

Example 554:

5'-((2-Pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it, enantiomer A and enantiomer B

15,0 mg 5'-((2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it is obtained in the same manner as in example 162 (stage 2)-(stage 7), but using 5'-hydroxy-2H-1,2'-bipyridine-2-it, share with columns for the separation of optical isomers (CHIRALPAK AD 2 cmϕ× 25 L (Daicel Chemical), mobile phase: 2-propanol, flow rate: 10 ml/min), the enantiomer A (retention time: 23,6 min) and enantiomer B (time derivan the I: 50,7 min), each in the form of a solid of light yellow color.

Example 555:

5'-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it, enantiomer A

0.003 ml of acetic anhydride are added to a solution in chloroform (1 ml) of 6.5 mg of enantiomer A 5'-((2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-she obtained in example 554, and the reaction liquid was stirred at room temperature for 30 minutes. The reaction solvent is evaporated and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), receiving one chiral form specified in the connection header in the form of a solid white color.

1H NMR (CD3OD) δ: 1,91 and 2.16 (total 3H, each s), 1,94-of 2.20 (3H, m), 2,32-2,52 (1H, m), 3,63-3,98 (2H, m), 5,38-5,44 (1H, m), of 6.49-is 6.54 (1H, m), 6,63 of 6.68 (1H, m), 7.23 percent-7,58 (3H, m), 7,60-to 7.67 (2H, m), to 7.77 (1H, DD, J=8,8, to 15.8 Hz), 7,87-to 7.93 (1H, m), 7.95 is shed 8.01 (1H, m), 8,27-8,31 (1H, m), to 8.41 (1H, d, J=2,9 Hz), 8,73 (1H, t, J=4,7 Hz)

ESI-MS (m/e): 493[M+H]

Example 556:

5'-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it, enantiomer B

0.003 ml of acetic anhydride are added to a solution in chloroform (1 ml) of 5.8 mg of enantiomer B 5'-((2-pyridin-2-yl-6-pyrrolidin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-she obtained in example 554, and the reaction liquid was stirred at whom atoi temperature for 30 minutes. The reaction solvent is evaporated and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), receiving one chiral form specified in the connection header in the form of a solid white color.

ESI-MS(m/e): 493 [M+H]

Example 557:

6-(CIS-1-acetyl-4-ftorpirimidinu-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 325 (stage 6), or in accordance with the method or by combining with an ordinary method but using CIS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine obtained in example 325 (stage 5), and 4-(2-methyl-2H-tetrazol-5-yl)phenol.

1H NMR (CD3OD) δ: 1,80-2,84 (2H, m), 1,94 and 2.25 (total 3H, each s), 3,90-4,30 (2H, m), 4,43 (3H, s), 5,28-of 5.50 (1H, m), 5,51-5,59 (1H, m), 7.18 in-to 7.64 (5H, m), 7,94 shed 8.01 (1H, m), 8,12-8,18 (2H, m), 8,25-8,29 (1H, m), 8,70-8,77 (1H, m)

ESI-MS (m/e): 499[M+H]

Example 558:

3-(4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-he

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 483, or in accordance with the method or by combining with an ordinary method but using 3-(4-hydroxyphenyl)-1,3-oxazolidin the-2-it.

1H NMR (CDCl3) δ: 1,20-2,50 (7H, m), 3,50-4,00 (2H, m), 3,90-of 4.25 (2H, m), 4,40-4,60 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (7H, m), 7,80-8,00 (1H, m), 8,25-and 8.50 (1H, m), 8,50-8,80 (1H, m), 10,50-10,80 (1H, m)

ESI-MS (m/e): 484[M+H]

Example 559:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-methylpyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance in the same manner as in example 483, or in accordance with the method or by combining with an ordinary method but using 6-methylpyridin-3-ol.

1H NMR (CDCl3) δ: 1,72-2,59 (10H, m), 3,53-are 3.90 (2H, m), 5,20-of 5.55 (1H, m), for 6.81-7,66 (5H, m), 7,78-a 7.92 (1H, m), 8,28-8,43 (2H, m), 8,55-8,66 (1H, m), 11,07-for 11.55 (1H, m)

ESI-MS (m/e): 414[M+H]

Example 560:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-pyrazin-2-espiridion-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 483, or in accordance with the method or by combining with an ordinary method but using 6-pyrazin-2-espiridion-3-ol.

1H NMR (CDCl3) δ: 0,80-to 2.40 (7H, m), 3,60-are 3.90 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 7,00-7,80 (4H, m), 7,80-8,00 (1H, m), 8,30-of 8.50 (2H, m), 8,50-8,80 (4H, m), 9,50-to 9.70 (1H, m), the 10.40-10,80 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 561:

6-(CIS-1-acetyl-4-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance yellow is the first color in the same way, as in example 325 (stage 6), or in accordance with the method or by combining with an ordinary method but using CIS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine obtained in example 325 (stage 5), and 2'-forbiden-4-ol.

1H NMR (CDCl3) δ: 0,80 is 2.80 (6H, m), 3,80-and 4.40 (2H, m), of 5.05-of 5.50 (1H, m), 7,00-7,70 (11N, m), 7,75-of 7.95 (1H, m), 8,30-and 8.50 (1H, m), 8,50 is 8.75 (1H, m), or 10.60-10,80 (1H, m)

ESI-MS (m/e): 511[M+H]

Example 562:

6-(CIS-1-acetyl-4-ftorpirimidinu-2-yl)-5-(4-pyrazin-2-elfenix)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 325 (stage 6), or in accordance with the method or by combining with an ordinary method but using CIS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine obtained in example 325 (stage 5), and 4-pyrazin-2-kilfenora.

1H NMR (CDCl3) δ: 1,20 is 2.80 (6H, m), 3,80-and 4.40 (2H, m), 5,20-of 5.50 (1H, m), 7,00-of 7.70 (5H, m), 7,80-of 7.95 (1H, m), 7.95 is-to 8.20 (2H, m), 8,30-of 8.50 (2H, m), 8,50-8,80 (2H, m), 8,95-9,20 (1H, m), or 10.60-10,80 (1H, m)

ESI-MS (m/e): 495[M+H]

Example 563:

N-((5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridin-2-yl)methyl)ndimethylacetamide

Specified in the title compound obtained as an oily substance in the same manner as in example 483, or in accordance with the method or by combining with ordinary the m way but using N-((5-hydroxypyridine-2-yl)methyl)ndimethylacetamide.

1H NMR (CDCl3) δ: 1,83-2,47 (10H, m), 3,54-are 3.90 (2H, m), 4,48-4,59 (2H, m), to 5.21-of 5.50 (1H, m), 6,66-of 7.69 (6H, m), 7,79-to $ 7.91 (1H, m), 8.30 to-8,44 (2H, m), 8,54-8,69 (1H, m), 10,96-of 11.29 (1H, m)

ESI-MS (m/e): 471[M+H]

Example 564:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-herperidin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily yellow substance in the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-herperidin-3-ol.

1H NMR (CDCl3) δ: 1,40-of 2.50 (7H, m), 3,50-4,00 (2H, m), 5,00-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (5H, m), 7,80-of 7.95 (1H, m), 8,00-of 8.15 (1H, m), 8,25-and 8.50 (1H, m), 8,50-to 8.70 (1H, m), or 10.60-10,80 (1H, m)

ESI-MS (m/e): 418[M+H]

Example 565:

CIS-1-(4-fluoro-2-(6-(6-cyano-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon, enantiomer A and enantiomer B

(Stage 1) preparation of CIS-1-(4-fluoro-2-(6-(6-cyano-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

Specified in the header of the connection will receive the same manner as in example 325 (stage 6), or in accordance with the method or by combining with an ordinary method but using CIS-1-acetyl-2-(5-nitro-2-fluoro-4-((pyridine-2-carbonyl)amino)phenyl)-4-acetoxy-pyrrolidine obtained in example 325 (stage 5), and 6-cyano-pyridin-3-ol.

(Stage 2) receipt of the enantiomer A and enantiomer B of CIS-1-(4-fluoro-2-(6-(6-cyano-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone:

Specified in the header of the connection will receive the same manner as in example 333, or in accordance with the method or by combining with an ordinary method but using racemic CIS-1-(4-fluoro-2-(6-(6-cyano-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)ethanone obtained (stage 1).

Enantiomer A

1H NMR (CD3OD) δ: 1,91 (3H×1/2, s), 2,22 (3H×1/2, s), 2,32-to 2.67 (2H, m), 3.95 to 4,30 (2H, m), 5,27-vs. 5.47 (2H, m), 7,35-to 7.64 (3H, m), a 7.85-a 7.92 (1H, m), 7,97-to 7.99 (1H, m), 8,29 (1H, t, J=7,6 Hz), at 8.60 (1H, d, J=3.1 Hz), a total of 8.74 (1H, s),

ESI-MS (m/e): 443[M+H]

Enantiomer B

ESI-MS(m/e): 443 [M+H]

Example 566:

6-(1-Acetyl-3-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomer A

(Stage 1) to Obtain enantiomer A and enantiomer B of N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide:

300 mg of diastereoisomer B N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 493, share with columns for the separation of optical isomers (CHIRALCEL OD 2 cmϕx 25 L (Daicel Chemical), mobile phase: hexane/ethanol/diethylamine=50/50/0,1, flow rate: 10 ml/min) enantiomer A and enantiomer B, each in the form of a solid substances yellow color.

(Stage 2) to Obtain enantiomer A of 6-(1-acetyl-3-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole:

Specified in the header is the connection get in the same way, as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using enantiomer A of N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide and 2'-forbiden-4-ol.

1H NMR (CDCl3) δ: 1,82-2,43 (5H, m), 3,63 is 4.36 (2H, m), 5.25-in 5,70 (2H, m), 7,07-7,58 (11N, m), 7,74-of 7.90 (1H, m), 8,35-8,43 (1H, m), 8,58-8,68 (1H, m), 10,37-or 10.60 (1H, m)

ESI-MS (m/e): 511[M+H]

Example 567:

6-(1-Acetyl-3-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole, enantiomer B

Specified in the header of the connection will receive the same manner as in example 566 (stage 2), or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 566 (stage 1).

ESI-MS(m/e):511 [M+H]

Example 568:

CIS-1-(4-fluoro-2-(6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 565 (stage 1), or in accordance with the method or by combining with an ordinary method but using 4-econsultancy-phenol.

1H NMR (CD3OD) δ: 1,90 (3H×0,5, C), 2,22 (3H×0,5, C), 2,25-2,75 (2H, m), 3,88-4,39 (2H, m), 5,24-of 5.48 (2H, m), 7.23 percent to 7.75 (5H, m), of 7.90-8,02 (3H, m), 8,27-8,30 (1H, m), 8,73 is 8.75 (1H, m)

ESI-MS (m/e): 509[M+H]

Example 569:

3-(4-((6-(1-Acetyl who irreligion-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it, enantiomer A

(Stage 1) preparation of tert-butyl 2-(2-fluoro-4-((pyrazin-2-ylcarbonyl)amino)phenyl)pyrrolidin-1-carboxylate:

1.5 g of pyrazin-2-carboxylic acid and 3.1 g of monohydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide added to a solution in pyridine (50 ml) of 3 g of tert-butyl 2-(4-amino-2-fluoro-phenyl)pyrrolidin-1-carboxylate obtained in example 338 (step 2), and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting mentioned in the title compound as an oily yellow substance.

(Stage 2) obtaining the dihydrochloride of N-(3-fluoro-4-pyrrolidin-2-ylphenyl)pyrazin-2-carboxamide:

50 ml of 4n hydrochloric acid in dioxane are added to a solution in methanol (50 ml), 4.4 g of tert-butyl 2-(2-fluoro-4-((pyrazin-2-ylcarbonyl)amino)phenyl)pyrrolidin-1-carboxylate and the reaction liquid was stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure, obtaining specified in the title compound in the form of solids zelcogetvica.

(Stage 3) Obtaining N-(4-(1-acetylpyrrolidine-2-yl)-3-forfinal)pyrazin-2-carboxamide:

1.5 ml of acetic anhydride are added to a solution in pyridine (50 ml) 4.3 g of the dihydrochloride of N-(3-fluoro-4-pyrrolidin-2-ylphenyl)pyrazin-2-carboxamide and the reaction liquid was stirred at room temperature for 20 minutes. The reaction liquid was diluted with chloroform, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 4) to Obtain N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide:

40 ml of fuming nitric acid is added to a 3.9 g of N-(4-(1-acetylpyrrolidine-2-yl)-3-forfinal)pyrazin-2-carboxamide under ice cooling and the reaction liquid was stirred at room temperature for 2 hours. The reaction liquid was diluted with water with ice, alkalinized with a saturated aqueous solution of sodium bicarbonate and then extracted with chloroform. The organic layer was washed with a saturated solution of salt accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated PR is the reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=50/1), getting listed in the title compound as an oily yellow substance.

(Stage 5) to Obtain enantiomer A and enantiomer B of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide:

500 mg of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide share with columns for the separation of optical isomers (CHIRALPAK OD-H 2 cmϕ× 25 L (Daicel Chemical), mobile phase: hexane/2-propanol=1/1, flow rate: 15 ml/min), the enantiomer A (retention time: 18 min) and enantiomer B (retention time: 25 min)each in the form of an oily material light yellow color.

(Stage 6) to Obtain enantiomer A of 3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it:

One chiral form specified in the title compound obtained as an oily yellow substance in the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 3-(4-hydroxyphenyl)-1,3-oxazolidin-2-it enantiomer A of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide.

1H NMR (CDCl3) δ: 1,00-2,40 (7H, m), 3,50-are 3.90 (2H, m), 3,90-4,20 (2H, m), 4,40-4,60 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (6H, m), 8,50 is 8.75 (2H, m), 9,50-to 9.70 (1H, m), 10.30 a.m.-or 10.60 (1H, m)

ESI-MS (m/e): 485[M+H]

Example 570:

3-(4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-Benson Gasol-5-yl)oxy)phenyl-1,3-oxazolidin-2-it, enantiomer B

Specified in the title compound obtained as an oily yellow substance in the same method as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 3-(4-hydroxyphenyl)-1,3-oxazolidin-2-she and enantiomer B of N-(4-(1-acetylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide, obtained in example 569 (stage 5).

ESI-MS(m/e): 485 [M+H]

Example 571:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(cyclopropanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 483, or in accordance with the method or by combining with an ordinary method but using 4-(cyclopropanesulfonyl)phenol.

1H NMR (CDCl3) δ: 0,90-1,20 (2H, m), 1,20-1,40 (3H, m), 1.60-to 2,60 (7H, m), 3,50-4,00 (2H, m), of 5.05-of 5.50 (1H, m), 7,00-to 8.20 (8H, m), 8,30-and 8.50 (1H, m), 8,55-8,80 (1H, m), 10,70-11,20 (1H, m)

ESI-MS (m/e): 503[M+H]

Example 572:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(econsultancy)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 483, or in accordance with the method or by combining with an ordinary method but using 4-(econsultancy)phenol.

1H NMR (CDCl3) δ: 1,20-1,40 (3H, m), 1,60-2,50 (7H, m)3,00-320 (2H, m), 3,50-4,00 (2H, m), 5,10-of 5.50 (1H, m), 6.90 to-7,80 (5H, m), 7,80-of 8.00 (3H, m), 8,30-and 8.50 (1H, m), 8,50 is 8.75 (1H, m), or 10.60-11,20 (1H, m)

ESI-MS (m/e): 491[M+H]

Example 573:

CIS-1-(4-fluoro-2-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 565 (stage 1), or in accordance with the method or by combining with an ordinary method but using 6-econsultancy-pyridine-3-ol.

1H NMR (CD3OD) δ: 1,20-1,40 (3H, m), 1,90-of 2.30 (3H, m), 2.00 in 2,80 (2H, m), 3,20-3,50 (2H, m), 3,84-of 4.25 (2H, m), 5,27-of 5.45 (2H, m), 7,40-7,80 (4H, m), 8,00-to 8.20 (2H, m), 8,24-to 8.40 (1H, m), 8,66 (1H, s), 8,80 (1H, users)

ESI-MS (m/e): 510[M+H]

Example 574:

CIS-1-(4-fluoro-2-(6-(6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)alanon

Specified in the header of the connection will receive the same manner as in example 565 (stage 1), or in accordance with the method or by combining with an ordinary method but using 6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,90-of 2.30 (3H, m), 2.00 in 2,80 (2H, m)of 2.75 (3H, s), 3,84-and 4.40 (2H, m), and 5.30-of 5.45 (2H, m), 7,25-7,80 (4H, m), of 7.90-to 8.40 (3H, m), 8,55-8,68 (1H, m), is 8.75 (1H, s)

ESI-MS (m/e): 500[M+H]

Example 575:

5-((6-(1-Acetyl-3-ftorpirimidinu-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridine-2-carbonitrile

Specified in the title compound obtained as an oily substance in the same way, to the to in example 338 (step 5), or in accordance with the method or by combining with an ordinary method, but using the enantiomer B of N-(4-(1-acetyl-3-ftorpirimidinu-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 566 (stage 1), and 5-hydroxypyridine-2-carbonitrile.

1H NMR (CDCl3) δ: 1,54-of 2.45 (5H, m), 3,61-4,34 (2H, m), 5,09 is 5.54 (2H, m), 7,01-of 7.95 (6H, m), 8.34 per-of 8.47 (1H, m), 8,54-8,73 (2H, m), 10,66-10,79 (1H, m)

ESI-MS (m/e): 443 [M+H]

Example 576:

6-(1-Acetyl-3-ftorpirimidinu-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance in the same manner as in example 575, or in accordance with the method or by combining with an ordinary method but using 6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,54-of 2.45 (5H, m), 3,61-4,34 (2H, m), 5,09 is 5.54 (2H, m), 7,01-of 7.95 (6H, m), 8.34 per-of 8.47 (1H, m), 8,54-8,73 (2H, m), 10,66-10,79 (1H, m)

ESI-MS (m/e): 443[M+H]

Example 577:

6-(1-Acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-5-((6-pyrazin-2-espiridion-3-yl)oxy)-1H-benzimidazole

Specified in the title compound obtained as a light yellow oily substance in the same manner as in example 570, or in accordance with the method or by combining with an ordinary method but using 6-pyrazin-2-espiridion-3-ol.

1H NMR (CDCl3) δ: 1,05-of 2.50 (7H, m), 3,50-4,00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 7,00-7,80 (3H, m), 8,20-to 8.45 (1H, m, 8,45-8,80 (5H, m), 9,50-to 9.70 (2H, m), the 10.40-11,30 (1H, m)

ESI-MS (m/e): 479[M+H]

Example 578:

6-(1-Acetyl-5-methylpyrrolidine-2-yl)-5-((6-methylpyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method, but using N-(4-(1-acetyl-5-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide, obtained in example 545, and 6-methylpyridin-3-ol.

1H NMR (CDCl3) δ: 1,20-of 2.30 (7H, m), 2,30-2,70 (6H, m), 4,05-4,60 (1H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80 is 7.50 (4H, m), 7,70-of 7.90 (1H, m), 8,15-to 8.20 (1H, m), 8,25-to 8.40 (2H, m), 8,50-8,80 (1H, m)

ESI-MS (m/e): 428[M+H]

Example 579:

6-(1-Acetyl-5-methylpyrrolidine-2-yl)-5-((6-chloropyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 578, or in accordance with the method or by combining with an ordinary method but using 6-chloropyridin-3-ol.

1H NMR (CDCl3) δ: 1,20-2,60 (10H, m), 4,05 with 4.65 (1H, m), 5,10-of 5.50 (1H, m), 6,80-of 7.70 (4H, m), 7,80-8,10 (2H, m), 8,15-of 8.50 (2H, m), 8,60-8,80 (1H, m), 10,80-11,30 (1H, m)

ESI-MS (m/e): 448[M+H]

Example 580:

2-(5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridine-2-ylsulphonyl)ethanol

20 mg of 2-mercaptoethanol and 10 mg of potassium carbonate to relax the Ute to a solution in N,N-dimethylformamide (1 ml) 20 mg of 6-(1-acetylpyrrolidine-2-yl)-5-(6-chloropyridin-3-yl)oxy-2-pyridin-2-yl-1H-benzimidazole, obtained in example 504, and the reaction liquid was stirred at 120°C for 5 hours. After cooling, the reaction liquid was diluted with saturated aqueous sodium bicarbonate, extracted with chloroform and the organic layer was dried with magnesium sulfate and the solvent is evaporated under reduced pressure. The resulting residue is purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 1,10-of 2.50 (7H, m), 3,20-3,40 (2H, m), 3,50-4,00 (4H, m), 5,20-of 5.50 (1H, m), 6,80-of 7.70 (5H, m), 7,80-of 7.95 (1H, m), 8,10-of 8.50 (2H, m), 8,50-to 8.70 (1H, m), or 10.60-10,80 (1H, m)

ESI-MS (m/e): 476[M+H]

Example 581:

3-(5-((6-(1-Acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)pyridine-2-ylsulphonyl)ol-1-ol

Specified in the title compound obtained as a solid substance of white color in the same way as in example 580, or in accordance with the method or by combining with an ordinary method but using 3-mercaptopropyl-1-ol.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 3,20-3,40 (2H, m), 3,50-and 4.40 (6H, m), 5,20-the ceiling of 5.60 (1H, m), 6,80-of 7.70 (5H, m), 7,80-of 7.95 (1H, m), 8,20-of 8.50 (2H, m), 8,50-to 8.70 (1H, m), 10,80-11,20 (1H, m)

ESI-MS (m/e): 490 [M+H]

Example 582:

6-(1-Acetylpyrrolidine-2-yl)-2-(5-methylpyridin-2-yl)-5-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in is the head of the compound obtained as solid light yellow color in the same way, as in example 462, or in accordance with the method or by combining with an ordinary method but using 5-metilakrilovoe acid.

1H NMR (CD3OD) δ: 1,86 and 2.10 (total 3H, each s), 1,92 is 2.43 (4H, m), 2.65 and 2.66 per (total 3H, each s), 3.14, and and 3.16 (total 3H, each s), 3,62-of 3.96 (2H, m), 5.25-in, 5,32 (1H, m), 7.23 percent and 7,25 (total 2H, each d, J=8,8 Hz), 7,20-7,58 (3H, m), 7.95 and to 7.99 (total 2H, each d, J=8,8 Hz), scored 8.38-8,42 (1H, m), 9,12-9,16 (1H, m)

ESI-MS (m/e): 491[M+H]

Example 583:

6-(1-Acetylpyrrolidine-2-yl)-2-(5-methylpyrazine-2-yl)-5-(4-methanesulfonyl-phenoxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 462, or in accordance with the method or by combining with an ordinary method but using 5-methylpyrazine-2-carboxylic acid.

1H NMR (CD3OD) δ: 1,87-of 2.45 (7H, m), 2,66, and to 2.67 (total 3H, each s), 3.14, and and 3.16 (total 3H, each s), 3,63-4,00 (2H, m), 5,26-of 5.34 (1H, m), 7,20-to 7.61 (4H, m), of 7.96 and to 7.99 (total 2H, each d, J=8,8 Hz), 8,69 (1H, s), to 9.32 and 9,34 (total 1H, each s)

ESI-MS (m/e): 492[M+H]

Example 584:

1-(4-((6-(1-Acetyl-3-herperidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)alanon

Specified in the title compound obtained as an oily substance in the same manner as in example 575, or in accordance with the method or by combining with an ordinary method but using 1-(4-hydroxyphenyl)ethanone.

1H NMR(CDCl 3) δ: 1,62-2,60 (8H, m), 3,60-3,98, 4,04-4,33 (total 2H, each m), 5,11-to 5.56 (2H, m), 7,00-8,02 (8H, m), 8,33-8,48 (1H, m), 8,57-8,71 (1H, m), 10,76-11,09 (1H, m)

ESI-MS (m/e): 459[M+H]

Example 585:

6-(1-Acetyl-3-herperidin-2-yl)-5-((6-chloropyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance in the same manner as in example 575, or in accordance with the method or by combining with an ordinary method but using 6-chloropyridin-3-ol.

1H NMR (CDCl3) δ: 1,54-of 2.45 (5H, m), 3,60 is 4.35 (2H, m), 5,20-the ceiling of 5.60 (2H, m,), 6,90-7,00, 7,21-7,43, 7,60-7,93 ( total 6H, each m), by 8.22-to 8.45 (2H, m), 8,58-to 8.70 (1H, m), 10,63-10,90 (1H, m)

ESI-MS (m/e): 452[M+H]

Example 586:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily substance in the same manner as in example 570, or in accordance with the method or by combining with an ordinary method but using 6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,60-2,47 (7H, m), 2.57 m)-by 2.73 (3H, m), 3,57-3,93 (2H, m), to 5.21-of 5.48 (1H, m), 7,00-7,76 (3H, m), of 7.96-to 8.14 (1H, m), charged 8.52-8,68 (3H, m), 9,54 of-9.65 (1H, m,), 10,70-11,02, 11,53-10,66 ( total 1H, each m)

ESI-MS (m/e): 483[M+H]

Example 587:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(methanesulfonyl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily what about the matter in the same way, as in example 570, or in accordance with the method or by combining with an ordinary method but using 6-(methanesulfonyl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,51-2,47 (7H, m), 3,14-of 3.27 (3H, m), to 3.58-to 3.92 (2H, m), 5,14-of 5.40 (1H, m), 7.03 is-7,79 (4H, m), 7,95-8,11 (1H, m), 8,48-8,71 (2H, m), 9,56-to 9.66 (1H, m,), 10,65-10,94, 11,34-11,49 ( total 1H, each m)

ESI-MS (m/e): 479[M+H]

Example 588:

1-(4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)alanon

Specified in the title compound obtained as an oily substance in the same manner as in example 570, or in accordance with the method or by combining with an ordinary method but using 1-(4-hydroxyphenyl)ethanone.

1H NMR (CDCl3) δ: 1,53-2,61 (10H, m), 3,51-3,93 (2H, m), 5,14-vs. 5.47 (1H, m), 6,95-7,74 (4H, m), 7,88-8,02 (2H, m), 8,53-8,68 (2H, m), 9,54-to 9.66 (1H, m,), 10,60-10,88, 11,43-11,54 ( total 1H, each m)

ESI-MS (m/e): 442[M+H]

Example 589:

6-(1-Acetylpyrrolidine-2-yl)-5-((6-(deformedarse)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 338 (step 5)or in accordance with the method or by combining with an ordinary method but using 6-(deformedarse)pyridine-3-ol.

1H NMR (CD3OD) δ: 1,92 and 2.18 (total 3H, each s), 1,98-to 2.57 (4H, m), 3,65-4,00 (2H, m), 5,41-of 5.48 (1H, m), 7.03, and 7,07 (total 1H, each d, J=8,8 Hz), 7,00-7,72 (5H, m), 7,94-8,00 (1H, m), 8,08 1H, C)of 8.25 (1H, t, J=7.4 Hz), 8,73 (1H, s)

ESI-MS (m/e): 466[M+H]

Example 590:

6-(1-Acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-5-(4-pyrazin-2-elfenix)-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 4-pyrazin-2-kilfenora.

1H NMR (CDCl3) δ: 1,10-2,60 (7H, m), 3,50-4,00 (2H, m), 5,20-the ceiling of 5.60 (1H, m), 6,70-7,80 (4H, m), of 7.90-to 8.20 (2H, m), 8,50-8,80 (4H, m), 8,95-9,20 (1H, m), 9,50 is 9.75 (1H, m), or 10.60-11,40 (1H, m)

ESI-MS (m/e): 478[M+H]

Example 591:

4-((6-(1-Acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)benzonitrile

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 526, or in accordance with the method or by combining with an ordinary method but using 4-cyanophora.

1H NMR (CDCl3) δ: 1,50-2,50 (7H, m), 3,50-are 3.90 (2H, m), of 5.05-of 5.50 (1H, m), 6,65-7,80 (6H, m), 8,50-8,80 (2H, m), 9,50-to 9.70 (1H, m), the 10.40-11,20 (1H, m)

ESI-MS (m/e): 425[M+H]

Example 592:

Methyl 4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)benzoate

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 526, or in accordance with the method or by combining with an ordinary method, but using methyl 4-hydroxybenzo the A.

1H NMR (CDCl3) δ: 1,60-2,50 (7H, m), 3,50-4,00 (5H, m), 5,10-the ceiling of 5.60 (1H, m), 6,70-7,80 (4H, m), of 7.90-to 8.20 (2H, m), 8,50-to 8.70 (2H, m), 9,50-to 9.70 (1H, m), or 10.60-11,60 (1H, m)

ESI-MS (m/e): 458[M+H]

Example 593:

2-(5-((2'-Forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxamid

Specified in the title compound obtained as solid light yellow color in the same way as in example 182, or in accordance with the method or by combining with an ordinary method but using 2'-forbiden-4-ol.

1H NMR (DMSO-d6) δ: 1,60-2,60 (4H, m), 3,20-4,20 (2H, m), 5,10-and 5.30 (1H, m), the ceiling of 5.60-5,90 (2H, m), 6.90 to-7,70 (11N, m), of 7.90-8,10 (1H, m), 8,20-to 8.40 (1H, m), 8,60-8,80 (1H, m)

ESI-MS (m/e): 494[M+H]

Example 594:

6-(1-Acetylpyrrolidine-2-yl)-5-(4-(5-methyl-[1,2,4]-oxadiazol-3-yl)phenoxy-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as a solid substance of white color in the same way as in example 526, or in accordance with the method or by combining with an ordinary method but using 4-(5-methyl-[1,2,4]-oxadiazol-3-yl)phenol.

1H NMR (CDCl3) δ: 1,60 is 2.80 (10H, m), 3,50-4,00 (2H, m), 5,15-the ceiling of 5.60 (1H, m), 6,70-7,80 (5H, m), of 7.90-to 8.20 (2H, m), 8,50-to 8.70 (1H, m), 9,50-to 9.70 (1H, m), or 10.60-11,50 (1H, m)

ESI-MS (m/e): 482[M+H]

Example 595:

6-((2R,5S)-1-Acetyl-5-methylpyrrolidine-2-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

(Stage 1) preparation of 2-fluoro-N-methoxy-N-methylbenzamide:

5,79 g hydrochloride-methoxy-N-methylamine and 12.4 g of the hydrochloride of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide is added to the suspension in pyridine (80 ml) 10 g of 2-fluoro-4-nitrobenzoic acid and the reaction liquid was stirred overnight at room temperature. The pyridine is evaporated under reduced pressure and water is added. The precipitate is collected by filtration, washed with water and dried, obtaining mentioned in the title compound in the form of a solid of light yellow color.

(Stage 2) Obtain 4-amino-2-fluoro-N-methoxy-N-methylbenzamide:

15.2 g of ammonium chloride and 8 g of iron powder is added to the suspension 10,84 g of 2-fluoro-N-methoxy-N-methylbenzamide in 60 ml of methanol and 30 ml of water and the reaction liquid is refluxed for 3 hours. The reaction liquid was filtered through Celite and the solvent is evaporated under reduced pressure. The obtained residue was diluted with ethyl acetate, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1 to 1/2), getting mentioned in the title compound as an oily substance brown.

(Stage 3) Obtaining N-(3-fluoro-4-((N-methoxy-N-methylamino)carbonyl)phenyl)pyrazin-2-carboxamide:

2,56 g pyrazin-2-carboxylic acid and of 4.66 g of the hydrochloride of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide are added to a solution in pyridine (20 ml) and 3.7 g of 4-amino-2-fluoro-N-methoxy-N-methylbenzamide and the reaction liquid was stirred at room temperature for 1 hour is. The pyridine is evaporated under reduced pressure, the residue diluted with ethyl acetate, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained solid was washed with a mixed solvent of ethyl acetate and hexane, obtaining mentioned in the title compound in the form of a solid of light yellow color.

(Stage 4) to Obtain N-(4-((4R)-4-((tert-butyl(dimethyl)silyl)oxy)-2-pentanoyl)-3-forfinal)pyrazin-2-carboxamide:

in 10.8 ml of n-butyl lithium (2,46 M solution in hexane) are added to a solution in tetrahydrofuran (80 ml) to 4.92 g of (3R)-3-(tert-butyl(dimethyl)silyl)hydroxy-1-butyne at -78°C and the reaction liquid was stirred at the same temperature for 1 hour. Solution in tetrahydrofuran (60 ml) 2.7 g of N-(3-fluoro-4-((N-methoxy-N-methylamino)carbonyl)phenyl)pyrazin-2-carboxamide add to it when -78°C and the reaction liquid is heated to room temperature and stirred for 2 hours. Water added to the reaction liquid, extracted with ethyl acetate and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1-1/1), getting mentioned in the title compound in the form of a solid yellow color.

(Stage 5) Recip is of N-(4-((4R)-4-((tert-butyl(dimethyl)silyl)oxy)pentanoyl)-3-forfinal)pyrazin-2-carboxamide:

100 mg of the catalyst 10% palladium on coal added to a solution of 513 mg of N-(4-((4R)-4-((tert-butyl(dimethyl)silyl)oxy)-2-pentanoyl)-3-forfinal)pyrazin-2-carboxamide in 5 ml of tetrahydrofuran and 20 ml of ethanol and the reaction liquid is stirred in hydrogen atmosphere for 1.5 hours. The catalyst was removed by filtration, the solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1 to 1/1)to give specified in the title compound in the form of solid light yellow color.

(Stage 6) to Obtain N-(4-((4R)-1,4-dihydroindole)-3-forfinal)pyrazin-2-carboxamide:

89 mg of sodium borohydride are added to a solution of 340 mg of N-(4-((4R)-4-((tert-butyl(dimethyl)silyl)oxy)pentanoyl)-3-forfinal)pyrazin-2-carboxamide in a mixture of 10 ml of methanol and 5 ml of tetrahydrofuran and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid is distilled under reduced pressure and the residue diluted with ethyl acetate, washed with aqueous saturated solution of ammonium chloride and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to give crude product. of 1.18 ml of tetrabutylammonium fluoride (1 M solution in tetrahydrofuran) are added to a solution in tetrahydrofuran (6 ml) and the resulting crude productare ice cooling and the reaction liquid was stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1 to ethyl acetate), obtaining mentioned in the title compound in the form of a solid of light yellow color.

(Stage 7) to Obtain N-(4-((5S)-1-acetyl-5-methylpyrrolidine-2-yl)-3-forfinal)pyrazin-2-carboxamide:

of 0.26 ml of triethylamine and 0.11 ml methanesulfonyl chloride is added to the suspension in chloroform (6 ml) 147 mg of N-(4-((4R)-1,4-dihydroindole)-3-forfinal)pyrazin-2-carboxamide and the reaction liquid was stirred at room temperature for 2 hours. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to give crude product. 30 mg of sodium azide are added to a solution in dimethylformamide (4 ml) of the obtained crude product under ice cooling and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate, washed with water and saturated salt solution accordingly and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to give crude product. 15 mg of the pentahydrate of copper sulfate and 52 mg of sodium borohydride we use the t to a solution in methanol (5 ml) of the obtained crude product, and the reaction liquid was stirred at room temperature for 2 hours. Add 35 mg of sodium borohydride and the reaction liquid is stirred for 30 minutes. 35 mg of sodium borohydride is added and the reaction liquid is stirred for 30 minutes. The solvent is evaporated and the residue was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to give crude product. 0,043 ml of acetic anhydride are added to a solution in chloroform (4 ml) of the obtained crude product, the solvent is evaporated under reduced pressure and the residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), ethyl acetate/methanol=10/1), getting mentioned in the title compound as an oily material light yellow color.

(Stage 8) Obtaining N-(4-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide:

1 ml of fuming nitric acid is added to 59 mg of N-(4-((5S)-1-acetyl-5-methylpyrrolidine-2-yl)-3-forfinal)pyrazin-2-carboxamide at room temperature and the reaction mass is stirred at the same temperature for 30 minutes. The reaction liquid was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the product purified races is the defining thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (Merck), ethyl acetate), obtaining mentioned in the title compound as an oily material light yellow color. (Rf: TRANS form>CIS form.)

(Stage 9) to Obtain 6-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole:

9,2 mg 4-methanesulfonyl-phenol and 26.2 mg of cesium carbonate are added to a solution of N-methylpyrrolidinone (1 ml) of 10.4 mg of N-(4-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide and the reaction liquid was stirred at 90°C for 1 hour. Add 60 mg of the dihydrate of tin chloride (II) and the reaction liquid was stirred at 90°C for 1 hour and at 100°C for 2 hours. The ethyl acetate and aqueous saturated sodium hydrogen carbonate solution is added to the reaction liquid, the precipitate is removed by filtration, the remaining liquid is extracted with ethyl acetate and the organic layer washed with water and saturated salt solution accordingly and the extract is dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and purify the distribution of thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1), getting mentioned in the title compound as an oily material light yellow color.

1H NMR (CDCl3) δ: 1.31 and 1.33 full (total 3H, each d, J=6.0 Hz), 1.55V to 2.6 (7H, m), 3,03-3,10 (3H, m), 4,25-to 4.62 (1H, m), 5,20-5,44 (1H, m), 7,01-to 7.68 (4H, m), a 7.85-of 7.97 (2H, m), 8,57-8,69 (2H, m), 9,56-9,63 (1H, m)

ESI-MS (m/e): 492[M+H]

Example 596:

N-methyl-2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxetanone

Specified in the title compound obtained as an oily yellow substance in the same manner as in example 498 (stage 5)-(stage 8), or in accordance with the method or by combining with an ordinary method but using 2-methyl-2H-tetrazol-5-kilfenora.

1H NMR (CDCl3) δ: 1,80-of 2.50 (7H, m), 2,90-4,00 (4H, m), 4,30-4,50 (3H, m), 5,10-the 5.65 (1H, m), 7,10 (2H, m), 7,20-a 7.85 (3H, m), 7,80-of 7.95 (1H, m), 8,05-to 8.20 (2H, m), 8,30-and 8.50 (1H, m), 8,50-to 8.70 (1H, m)

ESI-MS (m/e): 510[M+H]

Example 597:

6-(1-Acetylpyrrolidine-2-yl)-5-((4'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 483, or in accordance with the method or by combining with an ordinary method but using 4'-forfinal-4-ol.

1H NMR (CDCl3) δ: 1,66 is 2.43 (7H, m), 3,44-to 3.92 (2H, m), to 5.21-the ceiling of 5.60 (1H, m), 6,80-to 7.67 (1 1H, m), to 7.77-to $ 7.91 (1H, m), 8.30 to-8,43 (1H, m), 8,53-8,67 (1H, m), 10,89-11,43 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 598:

6-(1-Acetylpyrrolidine-2-yl)-5-((3'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow CEE is and in the same way, as in example 483, or in accordance with the method or by combining with an ordinary method but using 3'-forfinal-4-ol.

1H NMR (CDCl3) δ: 1,67-2,44 (7H, m), 3,44-to 3.92 (2H, m), 5,22-to 5.58 (1H, m), 6,92-7,68 (11N, m), 7,78-to 7.93 (1H, m), 8,33-to 8.45 (1H, m), 8,56-8,68 (1H, m), 10,88-11,38 (1H, m)

ESI-MS (m/e): 493[M+H]

Example 599:

2-(5-((6-Cyano-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxamid

Specified in the title compound obtained as a solid substance of white color in the same manner as in example 162 and example 182, or in accordance with the method or by combining with an ordinary method but using 6-cyano-3-ol.

1H NMR (CD3OD) δ: 1,80-2,20 (3H, m), 2,20-of 2.50 (1H, m), 3,40-of 3.60 (1H, m), 3,70-of 3.80 (1H, m), 4.80 to and 5.30 (1H, m), 6,60 to 6.75 (2H, m), 7,20-of 7.70 (3H, m), 7,80-to 8.20 (3H, m), 8,20-8,30 (1H, m), 8,50-8,65 (1H, m), 8,70-8,80 (1H, m)

ESI-MS (m/e): 426[M+H]

Example 600:

6-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 595 (stage 9), or in accordance with the method or by combining with an ordinary method, but using N-(4-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide, obtained in example 595 (stage 8), and 4-(5-methyl-[1,2,4]-oxadiazol-3-yl)phenol.

1H the Mr (CDCl 3) δ: of 1.33 and 1.34 (total 3H, each d, J=6.0 Hz), 1,55-2,60 (7H, m), of 2.68 and 2.70 (total 3H, each s), 4.26 deaths-to 4.62 (1H, m), 5,28-5,49 (1H, m), 7.03 is-to 8.12 (4H, m), 8,40-8,69 (3H, m), to 9.57-9,63 (1H, m)

ESI-MS (m/e): 497 [M+H]

Example 601:

6-(1-Acetylpyrrolidine-2-yl)-2-(5-methylpyrazine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-1H-benzimidazole

Specified in the title compound obtained as solid light yellow color in the same way as in example 306, or in accordance with the method or by combining with an ordinary method but using 4-(2-methyl-2H-tetrazol-5-yl)phenol and 5-methylpyrazine-2-carboxylic acid.

1H NMR (CD3OD) δ: 1,88-2,48 (7H, m), 2.63 in and 2.64 (total 3H, each s), 3,61-3,99 (2H, m), to 4.41 and was 4.42 (total 3H, each s), lower than the 5.37-5,4 (1H, m), 7,15-of 7.55 (2H, m), 7,17 (2H, d, J=8,8 Hz), 8,08 and 8,11 (total 2H, each d, J=8,8 Hz)8,64 (1H, s), 9,27 and 9,29 (total 1H, each s)

ESI-MS (m/e): 496[M+H]

Example 602:

6-(1-Acetyl-4-methylpyrrolidine-2-yl)-5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole

(Stage 1) preparation of N-(3-fluoro-4-(3-methyl-3-butenyl)phenyl)pyridine-2-carboxamide:

9,89 ml chloride (2-methyl-2-propen-1-yl)magnesium (0,50 M solution in tetrahydrofuran) are added to a solution in tetrahydrofuran (10 ml) 500 mg N-(3-fluoro-4-((methoxy(methyl)amino)carbonyl)phenyl)pyridine-2-carboxamide, obtained in the same manner as in example 145 (stage 3), or in accordance with the method or by combining with the usual way, but with ispolzovaniem-2-carboxylic acid under ice cooling. The reaction liquid is stirred for 3 hours while cooling with ice and then water was poured into the reaction solution, extracted with ethyl acetate and the extract is dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=3/1)to give specified in the header of the connection.

(Stage 2) Obtaining N-(3-fluoro-4-(1-hydroxy-3-methyl-3-butene-1-yl)phenyl)pyridine-2-carboxamide:

88,8 mg of sodium borohydride are added to a solution in methanol (5 ml) 280 mg of N-(3-fluoro-4-(3-methyl-3-butenyl)phenyl)pyridine-2-carboxamide. The reaction liquid was stirred at room temperature for 3 hours and then poured into aqueous saturated solution of ammonium chloride, extracted with ethyl acetate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=2/1)to give specified in the header of the connection.

(Stage 3) Obtaining N-(4-(1,4-dihydroxy-3-methylbutyl)-3-forfinal)pyridine-2-carboxamide:

1,20 ml of the complex of borane and metilsulfate (1 M solution in dichloromethane) is added to the solution in tetrahydrofuran (5 ml) 0,082 ml of cyclohexene are added while cooling with ice. The reaction liquid per mesilat for 10 minutes while cooling with ice and add it to the solution in tetrahydrofuran (3 ml) 301 mg of N-(3-fluoro-4-(1-hydroxy-3-methyl-3-butene-1-yl)phenyl)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 1 hour. 0,50 ml of aqueous 5N sodium hydroxide solution and aqueous 35% solution of hydrogen peroxide added to the reaction liquid, and stirred at room temperature for 10 minutes. The reaction liquid was poured into aqueous saturated solution of ammonium chloride, extracted with ethyl acetate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: chloroform/methanol=9/1)to give specified in the header of the connection.

(Stage 4) to Obtain N-(3-fluoro-4-(4-methylpyrrolidine-2-yl)phenyl)pyridine-2-carboxamide:

of 0.62 ml of triethylamine and 0.23 ml methanesulfonyl chloride are added to a solution in chloroform (5 ml) 236 mg of N-(4-(1,4-dihydroxy-3-methylbutyl)-3-forfinal)pyridine-2-carboxamide under ice cooling and the reaction mass stirred at room temperature for 3 hours. The reaction liquid was poured into aqueous saturated solution of sodium bicarbonate, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product. to 53.0 mg of sodium azide added under ice cooling to a solution in dimethylformamide (3 ml) of the obtained crude product. The reaction liquid is stirred for 30 minutes while cooling l the house and stirred at room temperature for 3 hours. The reaction mass is diluted with ethyl acetate, washed with water and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product. 20 mg of the pentahydrate of copper sulfate and 168 mg of sodium borohydride are added to a solution in methanol (4 ml) of the obtained crude product. The reaction mass was stirred at room temperature for 4 hours and then poured into aqueous saturated solution of sodium bicarbonate, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to give crude product. 0,050 ml of acetic anhydride are added to a solution in chloroform (3 ml) of the obtained crude product, and the reaction liquid was stirred at room temperature for 30 minutes. The solvent is evaporated under reduced pressure and the residue purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/3)to give specified in the header of the connection.

(Stage 5) to Obtain N-(4-(1-acetyl-4-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide:

1 ml of fuming nitric acid is added to 70,7 mg of N-(3-fluoro-4-(4-methylpyrrolidine-2-yl)phenyl)pyridine-2-carboxamide and the reaction liquid was stirred at room temperature for 10 minutes. The reaction liquid was poured into aqueous saturated solution of hydroc is rbonate sodium, extracted with ethyl acetate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/2)to give specified in the header of the connection.

(Stage 6) Receiving 6-(1-acetyl-4-methylpyrrolidine-2-yl)-5-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole:

13,4 mg of 4-(methanesulfonyl)of phenol and of 44.9 mg of cesium carbonate are added to a solution in N-methyl-pyrrolidinone (2 ml) 15 mg of N-(4-(1-acetyl-4-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyridine-2-carboxamide and the reaction liquid was stirred at 90°C for 1 hour. 43,8 mg chloride dihydrate tin is added to the reaction liquid, then heat it to 100°C and stirred for 2 hours. The reaction liquid was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue purified distributing thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1), getting mentioned in the title compound in the form of a solid white color.

1H NMR (CDCl3) δ: 0,80-2,63 (9H, m), 3.00 and-and 4.40 (2H, m), 3.05, and is 3.08 (total 3H, each s), 5,03-5,43 (1H, m), 7,00-7,73 (5H, m), 7,83-7,98 (3H, m), 8,33-8,43 (1H, m), 8,62-to 8.70 (1H, m, to 10.62-10,80 (1H, m)

ESI-MS (m/e): 491[M+H]

Example 603:

6-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-((6-(methoxymethyl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole

Specified in the title compound obtained as an oily material light yellow color in the same way as in example 595 (stage 9), or in accordance with the method or by combining with an ordinary method, but using N-(4-((2R,5S)-1-acetyl-5-methylpyrrolidine-2-yl)-5-fluoro-2-nitrophenyl)pyrazin-2-carboxamide, obtained in example 595 (stage 8), and 6(methoxymethyl)pyridine-3-ol.

1H NMR (CDCl3) δ: 1,10-2,22 (10H, m), 3,48, and a 3.50 (total 3H, each s), 4.26 deaths-to 4.62 (1H, m), of 4.57 and 4.59 (total 2H, each s), 5,33-5,52 (1H, m), 7,20 is 7.50 (4H, m), 8,40-to 8.70 (3H, m), to 9.57-9,63 (1H, m)

ESI-MS (m/e): 459[M+H]

Comparative example 1:

[1,2,4]Thiadiazole-5-carboxylic acid

2 ml of dimethylacetal N,N-dimethylformamide are added to a solution in chloroform (10 ml) of 1 g of ethyl thiooxamate and the reaction liquid was stirred at room temperature for 4 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1 to 1/2)to give 1.1 g of the compound of amidine in the form of an oily material red color.

A solution in ethanol (20 ml) 721 mg of hydroxylamine-O-sulfonic acid are added to a solution in ethanol (18 ml) 1,09 g soy is inane of amidine and 0.95 ml of pyridine and the reaction liquid was stirred overnight at room temperature. The solvent is evaporated under reduced pressure and the residue diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1)to give ethyl [1,2,4]thiadiazole-5-carboxylate as an oily material light yellow color. 5,7 ml aqueous 1N solution of sodium hydroxide are added to a solution in methanol (8 ml) 300 mg of the obtained ethyl [1,2,4]thiadiazole-5-carboxylate and the reaction liquid was stirred overnight at room temperature. The reaction liquid is distilled under reduced pressure and the residue is neutralized 2n hydrochloric acid. The reaction liquid is distilled under reduced pressure and the residue is washed with a mixture of chloroform/methanol=10/1 obtained organic layer is distilled under reduced pressure, obtaining mentioned in the title compound in the form of a solid white color.

Comparative example 2:

2 Deformedarse-pyridine-3-ol

2.1 g of sodium carbonate and 1,24 ml diverticulitisuses acid added to the suspension in acetonitrile (40 ml) of 2 g of 3-benzyloxy-2-hydroxypyridine and the reaction mass was stirred at room temperature for 1 hour and then rest ritel is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed with water and dried with anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=9/1 to 4/1)to give deformedarse connection in the form of an oily material light yellow color. 500 mg of the catalyst 10% palladium on coal are added to a solution in methanol (25 ml) of 2.38 g deformedarse connection and the reaction liquid is stirred in hydrogen atmosphere at room temperature for 1 hour. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure, obtaining mentioned in the title compound as an oily substance light purple color.

Comparative example 3:

6-Methanesulfonyl-pyridine-3-ol

6.6 g of bis(pinacolato)Debora, 5.9 g potassium acetate and 980 mg of the complex (1,1'-bis(diphenylphosphino)ferrocene)dichloropalladium (II) and dichloromethane are added to a solution in dimethyl sulfoxide (80 ml) 4,72 g 3-bromo-6-methanesulfonyl-pyridine and the reaction liquid was stirred at 80°C for 2 hours. The ethyl acetate and water added to the reaction liquid, insoluble substance is removed by filtration through Celite and the organic layer separated. The organic layer is washed with water and saturated salt solution appropriate about the time and dried with anhydrous magnesium sulfate, the solvent is evaporated under reduced pressure. 60 ml of aqueous 5 n sodium hydroxide solution and 30 ml of aqueous 30% solution of hydrogen peroxide are added to a solution in tetrahydrofuran (200 ml) of the obtained residue at 0°C and the reaction mass is stirred over night at room temperature. The reaction liquid was diluted with diethyl simple ether and washed with water. The aqueous layer was acidified with 5N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and the solvent is evaporated under reduced pressure. The obtained residue was washed with a mixed solvent of chloroform and hexane, obtaining mentioned in the title compound in the form of a solid brown color.

Comparative example 4:

6-Econsultancy-pyridine-3-ol

Specified in the header of the connection receives the same way as in comparative example 3, or in accordance with the method or by combining with an ordinary method but using 3-chloro-6-econsultancy-pyridine.

Comparative example 5:

Methoxy-methylamide (2R,4R)-4-hydroxy-pyrrolidin-2-carboxylic acid

(Stage 1) preparation of 1-benzyl ether complex (2R,4R)-4-(tert-butyl-diphenyl-silyloxy)pyrrolidine-1,2-dicarboxylic acid:

2,32 g of tert-butyldiphenylsilyl-chloride and 2,32 g of imidazole are added to a solution in dimethylformamide is (60 ml) 3,61 g of 1-benzyl ether complex (2R,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated solution of ammonium chloride and a saturated solution of salt accordingly and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/2)to give specified in the header of the connection.

(Stage 2) to Obtain benzyl (2R,4R)-4-(tert-butyl-diphenyl-silyloxy)-2-(methoxy-methyl-carbarnoyl)pyrrolidin-1-carboxylate:

1.50 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 761 mg of the hydrochloride of O,N-dimethylhydroxylamine add accordingly to the solution in pyridine (30 ml) 2,62 g of 1-benzyl ether complex (2R,4R)-4-(tert-butyl-diphenyl-silyloxy)pyrrolidine-1,2-dicarboxylic acid obtained in (stage 1), and the reaction liquid was stirred overnight at room temperature. The solvent of the reaction liquid is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/1)to give specified in the header of the connection.

(Stage 3) to Obtain benzyl (2R,4R)-4-hydroxy-2-methoxy-methyl-carbarnoyl-pyrrolidin-1-carboxylate:

7,46 ml of tetrabutylammonium fluoride (1 M solution in tetrahydrofuran is e) are added to a solution in tetrahydrofuran (30 ml) 2,04 g of benzyl (2R,4R)-4-(tert-butyl-diphenyl-silyloxy)-2-(methoxy-methyl-carbarnoyl)pyrrolidin-1-carboxylate, obtained (stage 2), and the reaction liquid was stirred at room temperature for 20 minutes. The solvent of the reaction liquid is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=1/3)to give specified in the header of the connection.

(Stage 4) Obtaining methoxy-methylamide (2R,4R)-4-hydroxy-pyrrolidin-2-carboxylic acid:

100 mg of the catalyst 10% palladium on coal are added to a solution in ethanol (20 ml) 600 mg of benzyl (2R,4R)-4-hydroxy-2-methoxy-methyl-carbarnoyl-pyrrolidin-1-carboxylate obtained in (stage 3), and the reaction liquid is stirred overnight in a hydrogen atmosphere. The catalyst was removed by filtration through Celite and the solvent is evaporated under reduced pressure, obtaining specified in the header of the connection.

INDUSTRIAL APPLICATION

Substituted benzimidazole derivatives of the formula (I-0) according to the invention have excellent activity of glucokinase and can be used in medicine for the treatment and/or prevention of diabetes, diabetic complications or obesity.

1. The compound of the formula (I-0)

or its pharmaceutically acceptable salt, where

X represents a carbon atom or a nitrogen atom;

X1, X2, X3and X4it is jdy independently represents a carbon atom or a nitrogen atom;

ring And formula (II)

is thiazolyl, imidazolyl, isothiazolin, thiadiazolyl, triazolyl, oxazolyl, oxadiazolyl, isoxazolyl, pyrazinyl, pyridyl, pyridazinyl, pyrazolyl or pyrimidinyl;

R1represents aryl or represents a 4 to 10-membered monocyclic or bicyclic heterokonta having in the ring 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and R1may be independently substituted by 1-3 R4and when specified heteroclita is aliphatic heterokonta, then it can have 1 or 2 double bonds;

R2independently represents hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6alkyl or -(CH2)1-4OH;

R3represents-C1-6alkyl, -(CH2)1-6-OH, -C(O)-OC1-6alkyl, -(CH2)1-6-OC1-6alkyl, -(CH2)1-6-NH2, cyano, -C(O)-C1-6alkyl, halogen, -C2-6alkenyl, -OS1-6alkyl, -COOH, -HE or oxo;

R4independently represents-C1-6alkyl, and the alkyl may be substituted by same or different 1 to 3 hydroxyl, halogen, -OC(O)-C1-6alkilani, and the alkyl may be substituted by 1-3 Halogens, or-OC1-6alkilani,

-C-7 cycloalkyl,

-C2-6alkenyl,

-C(O)-N(R51R52,

-S(O)2-N(R51R52,

-O-C1-6alkyl, and C1-6the alkyl may be substituted with halogen or N(R51R52,

-S(O)0-2-C1-6alkyl,

-C(O)-C1-6alkyl, C1-6the alkyl may be substituted with halogen, amino, CN, hydroxy, -O-C1-6by alkyl, -CH3-aFa, -OC(O)-C1-6by alkyl, -N(C1-6alkyl)C(O)O-C1-6by alkyl, -NH-C(O)O-C1-6the alkyl, phenyl, -N(R51R52, -NH-C(O)-C1-6by alkyl, -N(C1-6alkyl)-C(O)- C1-6the alkyl or-NH-S(O)0-2-C1-6the alkyl,

-C(S)-C3-7cycloalkyl,

-C(S)-C1-6alkyl,

-C(O)-O-C1-6alkyl,

-(CH2)0-4-N(R53)-C(O)-R54,

-N(R53)-C(O)-O-R54,

-C(O)-aryl, optionally substituted with halogen,

-C(O)-aromatic heterokonta,

-C(O)-aliphatic heterokonta,

heterokonta, and heterokonta may be substituted C1-6the alkyl, optionally substituted with halogen or-O-C1-6the alkyl,

phenyl, optionally substituted with halogen, -C1-6by alkyl, -O-C1-6the alkyl,

halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamino or nitro;

R51and R52each independently represent what possessing a hydrogen atom, C1-6alkyl or a nitrogen atom, R51and R52together form a 4-7-membered heterokonta;

R53represents a hydrogen atom or a C1-6alkyl,

R54represents-C1-6alkyl or

alkali for R53and R54and-N-C(O)- together form a 4-7-membered nitrogen-containing aliphatic heterokonta, or

alkali for R53and R54and-N-C(O)-O - together form a 4-7-membered nitrogen-containing aliphatic heterokonta, and aliphatic heterokonta may be substituted by oxo, or aliphatic heterokonta may have 1 or 2 double bonds in the ring;

X5represents-O-, -S-, -S(O)-, -S(O)2-, a single bond or-O-C1-6alkyl;

and independently indicates an integer of 1, 2 or 3;

q denotes an integer from 0 to 2;

m means an integer from 0 to 2,

except when one of X5represents-O-, -S-, -S(O)- or-S(O)2and the other of X5represents a single bond, and R1represents aryl, optionally substituted by 1-3 R4or nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, the case when X5both represent a single bond, or the case when R1both represent an aliphatic heterokonta.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, where X1-X4are all carbon atoms.

3. The compound according to claim 1 or its pharmaceutically acceptable salt, where X5represents-O-, -S-, -S(O)-, -S(O)2- or a single bond.

4. The compound according to claim 1, which is represented by formula (I-1)

or its pharmaceutically acceptable salt, where:

R11represents phenyl, optionally substituted by 1-3 R4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4; and X51represents-O-, -S-, -S(O)- or-S(O)2-; and other symbols have the above values.

5. The compound according to claim 4 or pharmaceutically acceptable salt, where R11both are finely, optionally substituted by 1-3 R4.

6. The compound according to claim 4 or pharmaceutically acceptable salt, where R11both are 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted 13 R 4.

7. The compound according to claim 4 or pharmaceutically acceptable salt, where one of R11means phenyl, optionally substituted by 1-3 R4and the other of R11represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4.

8. The compound according to claim 1, which is represented by formula (I-2)

or its pharmaceutically acceptable salt, where

R11represents phenyl, optionally substituted by 1-3 R4or represents 5 - or 6-membered nitrogen-containing aromatic heterokonta having from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and nitrogen-containing aromatic heterokonta may be substituted by 1-3 R4and

R12represents a 4-7-membered nitrogen-containing heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and

R12may be substituted by 1-3 R4and when hetero is also is aliphatic heterokonta, then it can have 1 or 2 double bonds;

X51represents-O-, -S-, -S(O)- or-S(O)2-;

X52represents-O-, -S-, -S(O)-, -S(O)2- or a single bond; and other symbols have the above values.

9. The compound of claim 8 or its pharmaceutically acceptable salt, where R12represents a 4-7-membered saturated nitrogen-containing aliphatic heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and a nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4and X52represents a single bond; or R12is a 5-7 membered nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds, and a 5-7 membered heterokonta may be substituted by 1-3 R4and X52represents-O-, -S-, -S(O)- or-S(O)2-.

10. The compound of claim 8 or its pharmaceutically acceptable salt, where R12is 47-membered saturated nitrogen-containing aliphatic heterokonta, having as heteroatom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and a nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4and X52represents a single bond.

11. The compound of claim 8 or its pharmaceutically acceptable salt, where R12is a 5-7 membered nitrogen-containing aliphatic heterokonta having as an atom constituting heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 or 2 double bonds, and a 5-7 membered heterokonta may be substituted by 1-3 R4and X52represents-O-, -S-, -S(O)- or-S(O)2-.

12. The compound of claim 8 or its pharmaceutically acceptable salt, where R12is a 5-7 membered nitrogen-containing aliphatic heterokonta, having as a heteroatom, comprising heterokonta at least one nitrogen atom and optionally having additional heteroatoms are 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, and having in the ring 1 is 2 double bonds, and nitrogen-containing aliphatic heterokonta may be substituted by 1-3 R4and X52means-Oh.

13. The compound according to claim 3 or pharmaceutically acceptable salt of formula (I-1), which is represented by formula (I-11)

and in the formula the symbols have the above values.

14. The connection 13 or its pharmaceutically acceptable salt, where X51they are both-O-.

15. The compound or pharmaceutically acceptable salt of formula (I-1), which is represented by formula (I-12)

and in the formula the symbols have the above values.

16. The connection 15 or a pharmaceutically acceptable salt, where X51they are both-O-.

17. The compound of claim 10 or its pharmaceutically acceptable salt, where R12represented by formula (III-1)

or the formula (III-2)

in the formulas, n means an integer from 1 to 3; R41has the same meanings as R4.

18. The compound according to any one of claims 1 to 17 or its pharmaceutically acceptable salt, where the ring a represents thiazolyl, thiadiazolyl, isoxazolyl, pyrazinyl, pyridyl, pyridazinyl, triazolyl or pyrazolyl, which can be substituted by 1-3 R4.

19. The compound of the formula (I-0), which is are the following connections:

5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-6-(2-carbarnoyl-phenoxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-(methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-(1-methyl-1H-pyrazole-3-yl)-1H-benzimidazole,

5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-phenoxy)-2-(1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,3-debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,4-debtor-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,5-debtor-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,6-debtor-Fenox is)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-(1-methyl-1H-pyrazole-3-yl)-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-herperidin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-herperidin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-chloropyridin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-chloropyridin-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-cyano-3-yloxy)-6-(6-acanaloniidae-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(2-deformedarse-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(2,6-debtor-phenoxy)-2-pyridin-2-yl-6-(6-methanesulfonyl-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-cyano-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5(2-fluoro-6-carbarnoyl-phenoxy)-2-pyridin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-carbarnoyl-phenoxy)-2-pyrazin-2-yl-6-(4-econsultancy-phenoxy)-1H-benzimidazole,

5-(2-fluoro-6-cyano-phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-fluoro-6-(tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-6-(6-econsultancy-pyridine-3-yloxy)-1H-benzimidazole,

5-(2-deformationen-3-yloxy)-6-(3-chloro-4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-fluoro-phenoxy)-2-(pyridin-2-yl)-6-(4-methanesulfonyl-phenoxy)-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(1-methyl-2-oxo-1,2-dihydro-pyridine-3-yloxy)-6-(4-econsultancy-phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2,6-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-(1H-pyrazole-3-yl)-1H-benzimidazole,

4-(2-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,3-debtor-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2,5-debtor-phenoxy)-6-(6-econsultancy-pyridine-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-1H-benzimidazole,

4-(2-cyano-6-fluoro-phenoxy)-6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(2-(6-(5-bromo-pyridine-2-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-hydroxymethyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-carboxamid,

2-hydroxy-1-(2-(6-(4-methanesulfonyl-1 phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

2-fluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-carbonitrile,

1-(2-(6-(4-meth is sulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-methylamino-Etalon,

1-(2-(6-(4-methanesulfonyl-phenoxy)-2-(1H-pyrazole-3-yl)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

1-(4-fluoro-2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

N-(5-(6-(1-acetyl-pyrrolidin-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yloxy)pyridine-2-yl)acetamide", she

1-(2-(2-(5-bromo-pyridine-2-yl)-6-(4-methanesulfonyl-phenoxy)-3H-benzimidazole-5-yl)pyrrolidin-1-yl)Etalon,

N-(2-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-1-yl)-2-oxo-ethyl)acetamide", she

6-(1-acetylpyrrolidine-2-yl)-5-(4-(methoxymethyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole monotropaceae,

1-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)pyridin-2(1H)-he,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

(2-(2-(5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl)methylamine,

6-(1-acetylpyrrolidine-2-yl)-5-((6-([1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

5-(1-acetyl-3-ftorpirimidinu-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-is)pyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

5-(1-acetyl-5-methylpyrrolidine-2-yl)-6-(4-(methanesulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(2-methyl-2H-tetrazol-5-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-(6-methoxypyridine-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxoethyl,

2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-carboxamid,

5'-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)-2H-1,2'-bipyridine-2-it,

3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyridin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it,

6-(1-acetylpyrrolidine-2-yl)-5-((6-methylpyridin-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-pyrazin-2-espiridion-3-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

6-(1-acetyl-3-ftorpirimidinu-2-yl)-5-((2'-forbiden-4-yl)oxy)-2-pyridin-2-yl-1H-benzimidazole,

3-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)-1,3-oxazolidin-2-it,

6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-5-((6-pyrazin-2-espiridion-3-yl)oxy)-1H-benzimidazole,

6-(1-acetylpyrrolidine-2-yl)-5-((6-(5-methyl-[1,2,4]-oxadiazol-3-yl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(4-((6-(1-acetylpyrrolidine-2-yl)-2-pyrazin-2-yl-1H-benzimidazole-5-yl)oxy)phenyl)Etalon,

6-(1-acetylpyrrolidine-2-yl)-5-(4-(5-methyl-[1,2,4]-oxadiazol-3-yl)phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

6-(1-acetyl-5-methylpyrrolidine-2-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole,

N-methyl-2-(2-(5-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-6-yl)pyrrolidin-1-yl)-2-oxetanone,

6-(1-acetyl-5-methylpyrrolidine-2-yl)-5-((6-(methoxymethyl)pyridine-3-yl)oxy)-2-pyrazin-2-yl-1H-benzimidazole,

1-(1-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon,

1-(1-(6-(6-methanesulfonyl-pyridine-3-yloxy)-2-pyridin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)Etalon,

1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)pyrrolidin-2-yl)alanon or

1-(1-(6-(6-econsultancy-pyridine-3-yloxy)-2-pyrazin-2-yl-3H-benzimidazole-5-yl)-4-fluoro-pyrrolidin-2-yl)alanon

or their pharmaceutically acceptable salts.

20. The pharmaceutical composition containing the following components (1)to(3), which is used for the treatment, prevention and/or delay the onset of type II diabetes:

(1) the compound according to any one of claims 1 to 19,

(a) any other activator of glucokinase,

(b) bis-guanin,

(c) a PPAR agonist,

(d) somatostatin,

(e) inhibitor α-glucosidase,

(f) insulin and

(g) an inhibitor of DPP-IV (dipeptidyl peptidases IV)

(3) a pharmaceutically acceptable carrier.

21. A glucokinase activator containing a compound or its pharmaceutically acceptable salt according to any one of claims 1 to 19 as its active ingredient.

22. Medicinal product for the treatment and/or prevention of diabetes, containing the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 20 as its active ingredient.

23. Drug and/or prophylactic agent against obesity, containing the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 20 as its active ingredient.



 

Same patents:

FIELD: chemistry; obtaining of medicinal preparations.

SUBSTANCE: description is given of a compound with general formula where R1 represents a halogen, C1-C6alkyl, CF3, CF2H or cyano, R2 represents C1-C6alkyl, R3 represents 5- or 6 - member hetero-aryl, optionally substituted with one, two or three substitutes, chosen from a group, consisting of a halogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkylhalogen, C1-C6alkoxy, NR'R", or substituted with a 1-morpholinyl group or substituted with thiomorpholinyl groups, 1-oxothiomorpholinyl or 1,1-dioxothiomorpholinyl; R', R" independently represent hydrogen, C1-C6alkyl, (CH2)0,1-(C3-C6)cycloalkyl, R represents hydrogen as well as its pharmaceutical salts and the method of obtaining them. The invention also relates to use of the given amidazole derivatives for obtaining medicinal preparations and to medicinal preparations containing them, meant for prevention or treatment of damages, through the mGluR5 receptor, such as acute and/or chronic neurologic damages, primarily shock pain, or for treatment of chronic and sharp pain.

EFFECT: obtaining of new compounds, with useful biological properties.

40 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of benzimidazol of the general formula I R1 designates phenyl group which unessentially contains up to three substitutors independently chosen of the group including F, Cl, Br, J, R4; R2 designates monocyclic or bicyclic 5-10-terms heteroaryl group which contains 1-2 heteroatoms, chosen of N, S and O; R3 designates H; R4 designatesC1-6alkyl; A designates C2-6 alkylene group; B designates group COOH, CONH2, CONHR5 or CONR5R5, in each case attached to atom of carbon of group A; R5 and R5 ' independently designate the residue chosen from group includingC1-6 alkyl where one C-atom can be replaced by O, and(C0-3 alkandiil-C3-7 cycloalkyl); and to their pharmaceutically acceptable salts, except for following compounds: 6 [[1-phenyl-2 (pyridine-4-il)-1H-benzimidazol-6-il] oxi] hexanic acid and 6 [[1-phenyl-2 (benzothien-2-il)-1H-benzimidazol-6-il] oxi] hexanic acid. The invention relates also to pharmaceuticals and to application of compounds of general formula I.

EFFECT: new biologically active compounds possess inhibiting effect on activation of microglia.

10 cl, 34 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl, naphthyl, 5-6-membered heterocyclyl comprising oxygen (O), nitrogen (N) or sulfur atom (S) as heteroatoms and wherein phenyl, naphthyl and heterocyclyl are optionally substituted with 1-3 substitutes chosen from halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy, nitro; di-(C1-C6)-alkylamino or (C1-C6)-alkoxy groups; R2 means hydrogen atom; R3 means (C1-C6)-alkyl or trifluoromethyl; A1 means C-R3 or nitrogen atom; A2 means piperidine or pyrrolidine wherein nitrogen atom in piperidine or pyrrolidine ring is added to A3 wherein A3 means -S(O)2- or -C(O)-; n = 0, 1 or 2. Also, invention relates to a pharmaceutical composition based on compounds proposed by the invention. Proposed compounds possess properties of NPY receptors antagonists and can be used in treatment arthritis, diabetes mellitus, nutrition disorders, obesity and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 1 tbl, 1 dwg, 26 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compound of the formula (I) possessing inhibitory effect on production of interleukin-12 (IL-12) wherein R1 represents group of the formula , aryl or heteroaryl; each among R2 and R4 represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy group; R3 represents Rc, alkenyl, -ORc, -OC(O)Rc, -SRc, -NRcCORd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcSO2Rd, -CORc, -C(O)ORc or -C(O)NRcRd; R5 represents hydrogen atom (H); n = 0, 1, 2, 3, 4, 5 or 6; X represents oxygen atom (O) or -NRc; Y represents a covalent bond. -CH2, O or -NRc; Z represents nitrogen atom (N); one of values U and V represents N and another represents -CRc; W represents O, sulfur atom (S) or -S(O)2 wherein each radical among Ra and Rb represents independently H, (C1-C6)-alkyl, aryl or heteroaryl; each radical among Rc and Rd represents independently H, (C1-C6)-alkyl, phenyl, heteroaryl, cyclyl, heterocyclyl or (C1-C6)-alkylcarbonyl wherein term "aryl" relates to hydrocarbon cyclic system (monocyclic or bicyclic) comprising at least one aromatic ring; term "heteroaryl" relates to hydrocarbon cyclic system (monocyclic or bicyclic) comprising at least one aromatic ring that comprises at least one heteroatom, such as O, N or S as a part of cyclic system and wherein other atoms mean carbon; term "cyclyl" and "heterocyclyl" relate to partially or completely saturated monocyclic or bicyclic system comprising from 4 to 14 carbons in rings wherein heterocyclic ring comprises one or some heteroatoms (for example, O, N or S) as part of cyclic system and wherein other atoms mean carbon, and under condition that when X represents -NH, Y represents a covalent bond, n = 0, and R3 represents H or CH3 then R1 doesn't mean thiazolyl or pyrimidinyl. Also, invention relates to a pharmaceutical composition and a method for treatment of disorder associated with hyperproduction of interleukin-12.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

49 cl, 43 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of pyrrolidinium of the general formula (I): possessing antagonistic effect with respect to muscarinic receptors M3 wherein B means phenyl or thienyl group; each radical among R1, R2 and R means independently hydrogen, fluorine, chlorine atom or hydroxyl; n means a whole number from 0 to 1; A means group chosen from groups -CH2 and -O-; m means a whole number from 0 to 6; R means (C1-C8)-alkyl; X- represents a pharmaceutically acceptable anion of mono- or multibasic acid, and involving all separate stereoisomers and their mixtures. Also, invention relates to methods for synthesis of such compounds, pharmaceutical compositions containing such compounds and to their using in therapy as antagonists of muscarinic receptors M3.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

17 cl, 51 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the formula (I) or their pharmaceutically acceptable salts wherein R1 and R2 are similar or different and chosen independently from group comprising aryl and heteroaryl. Each of them as a substitute comprises optionally from one to sic groups chosen from group comprising the following groups: (a) halogen atom; (b) -OCF3 or -OCHF2; (c) -CF3; (d) -CN; (e) alkyl; (f) R18-heteroaljyl; (k) hydroxyl; (l) alkoxyl comprising cyclopropylmethoxyl, and (s) trifluoroalkoxyl; R3 means hydrogen atom (H); R4, R5, R7 and R8 are similar or different and chosen independently from group comprising H, -OH, alkyl, heteroalkyl and

under condition that if Z and/or X means nitrogen atom (N) then all radicals R4, R5, R7 and R8 don't mean -OH; R6 means -C(O)R15; R9 and R10 mean H; R11 is chosen from group comprising H and alkyl; R12 is chosen from group comprising H and alkyl; R13 is chosen from group comprising alkyl and alkoxyl; R14 means H; R15 is chosen from group comprising -NR16R17, -OR16 and alkyl wherein R16 and R17 are similar or different and chosen independently from group comprising H and alkyl; R18 means a substitute chosen from group comprising lower alkyl, halogen alkyl, halogenalkyl, alkoxycarbonyl, dialkylamino-group and piperidinyl; X and Z are similar or different and chosen independently from carbon atom (C) and N. Proposed compounds possess properties of inhibitor of 17β-hydroxysteroid dehydrogenase of type 3. Also, invention describes a pharmaceutical composition based on compound of the formula (I).

EFFECT: valuable medicinal and biochemical properties of compound and pharmaceutical composition.

16 cl, 23 tbl, 651 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines represented by the formula (I): wherein n means 2, 3 or 4; R1 means hydrogen atom or alkyl with 1-4 carbon atoms; R2 means pyridyl or thiazolyl that can be substituted with alkyl with 1-4 carbon atoms, halogen atom, amino-, dimethylamino-, acetylamino-, guanidino-, pyridylamino-group, thienyl, pyridyl, morpholinyl and thiazolyl substituted if necessary with alkyl with 1-4 carbon atoms or phenyl comprising if necessary up to three substitutes as halogen atom, alkyl with 1-4 carbon atoms or alkoxy-group with 1-4 carbon atoms, and to their salts, hydrates, salt hydrates and solvates, and also to substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridine of the formula (I) possessing properties of agonist of A1-adenosine receptors. Also, invention describes a medicinal agent possessing properties of agonist of A1-adenosine receptors. Invention provides synthesis of novel compounds possessing valuable biological properties.

EFFECT: valuable medicinal and pharmacological properties of compounds and drug.

7 cl, 3 tbl, 27 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel nitrogen-containing aromatic derivatives of the general formula (I): wherein X1 means nitrogen atom (N) or group -CR10= wherein R10 means hydrogen atom (H), halogen atom or -CN; X2 means N or group -CR11= but X1 and X2 can't mean N simultaneously; Y means oxygen atom (O) or group -NRY- wherein RY means hydrogen atom or (C1-C6)-alkyl group; R1 means phenoxy-group, group -NR12aR12b, group , group and other values; each radical among R3, R4, R5, R6 and R11 means hydrogen atom; R7 means hydrogen atom or (C1-C6)-alkyl group; R8 means hydrogen atom or (C1-C6)-alkyl group; R10 means hydrogen atom, halogen atom or cyano-group; R9 means group -NR16aR16b or group of the formula: wherein T2 means pyrrolidine, piperazine ring possibly substituted with (C1-C6)-alkyl group, or morpholine ring; R12a and R12b mean independently hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; R2 means hydrogen atom or (C1-C6)-alkyl; R16a means hydrogen atom or (C1-C6)-alkyl, and R16b means (C1-C6)-alkyl possibly substituted with phenyl, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or di-(C1-C6)-alkylamino-group, (C3-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl possibly substituted with halogen atom, thiazolyl or piperidinyl possibly substituted with (C1-C6)-alkyl, and their salts or hydrates. Also, invention describes a pharmaceutical composition, method for treatment or prophylaxis of tumor diseases and using the novel compounds for preparing an agent useful in treatment abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method for treatment.

26 cl, 17 tbl, 221 ex