New 2-pyridinecarboxamide derivatives

FIELD: chemistry.

SUBSTANCE: invention pertains to new derivatives of 2-pyridinecarboxamide and their pharmaceutical salts, which have glucokinase activating properties. In formula (I): D represents O or S; R2 and R3 each represents a hydrogen atom; formula (II) represents triazole group, imidazole group, thiazole group and pyridine group, which can have in the ring, 1 or 2 substitutes; formula (III) represents a thiazole group, thiadiazole group, isoxazolyl group, pyrazine group, pyridothiazolyl group or pyridyl group, ring B can have 1 or 2 substitutes. The invention also relates to pharmaceutical compositions based on the invented compounds.

EFFECT: new derivatives can be used for treating such diseases as sugar diabetes.

19 cl, 5 tbl, 165 ex

 

The technical field to which the invention relates.

The present invention relates to activating glucokinase agent containing the derivative 2-pyridinecarboxamide as an effective component. In addition, it relates to new derivatives of 2-pyridinecarboxamide and their salts.

Background of invention

Glucokinase (GK) (ATP: D-hexose-6-phosphotransferase, EC 2.7.1.1) is one of the 4 types of hexokinase (glucokinase IV) in mammals. Econase is an activating enzyme for the first stage of the glycolytic pathway that catalyzes the reaction from glucose to glucose-6-phosphate. Location of glucokinase are mainly localized in the liver and beta cells of the pancreas, in which glucokinase control determines the speed stage of glucose metabolism, therefore it plays an important role in generalized metabolism of sugar. Glucokinase in the liver and glucokinase in the beta cells of the pancreas are the same in respect to their enzymatic properties, although the N-terminal sequence of 15 amino acids differ from each other in accordance with the difference splicing. 3 types of hexokinase (I, II and III), other than glucokinase, the enzyme activity is saturated when the concentration of glucose, 1 mmol or less, while a score of miles glitch the kinase to glucose is 8 mmol, the value which is closest to the physiological level of sugar in the blood. Therefore, the intracellular glucose metabolism is accelerated by glucokinase in response to changing blood sugar levels from normal (5 mmol) to occur after a meal increases (10-15 mmol).

Nearly 10 years ago has been hypothesized that glucokinase acts as a glucose sensor in the beta cells of the pancreas or the liver (Garfinkel D. and others, "Computer modeling identifies glucokinase as glukose sensor of panreatic beta-cells", American Journal Physilogy, 247, 3Pt2, 527-536 (1984)). Recently obtained results of the tests on mice, which glucokinase introduced by genetic engineering, it was found that glucokinase in fact plays an important role in generalized glucose homeostasis. Although mice in which the gene for glucokinase was destroyed, perish soon after birth (Grupe A. and others, "Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis", Cell, 83, 69-78 (1995)), the blood sugar level was reduced in normal and diabetic mice, in which glucokinase was generated in excess (Ferre, T. and others, "Correction of diabetic alterations by glucokinase", Proceedings of the National Academy of Sciences of the U.S.A., 93, 7225-7230 (1996)). With increasing concentration of glucose response of pancreatic beta-cells and hepatocytes favorably cause a reduced blood sugar levels, although the degree of reduction is, the meet is but different. Pancreatic beta cells to secrete more insulin, and, on the other hand, the liver absorbs sugar, and it accumulates in the form of glycogen, resulting in a decrease in the release of sugar.

Thus, the change in the enzymatic activity of glucokinase plays an important role in glucose homeostasis in mlekopitayushchikh due to liver and beta cells of the pancreas. In the case of emerging juvenile diabetes, which is called MODY2 (late diabetes of the young), found that the mutation occurs in the gene for glucokinase and reduced glucokinase increases the level of sugar in the blood (Vionnet N. and others, "a Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus", Nature Genetics, 356, 721-722 (1992)). Therefore, it is found that there is a close relationship that the mutation increases the activity of glucokinase and occurs hypoglycemia (Glaser B. and others, "Familial hyperinsulinism caused by an activating glucokinase mutation", New England Journal of Medicine, 338, 226-230 (1998)).

This means that glucokinase acts as a glucose sensor in humans and plays an important role in glucose homeostasis. On the other hand, take into account that a large number of patients with diabetes type II can regulate blood sugar levels by using the touch glucokinase system. Assume that activates glucokinase substances have an impact attributed the acceleration and insulin secretion in pancreatic beta-cells and impact in speeding up the absorption of sugar and inhibiting the release of sugar in the liver, and they are usually considered as therapeutic agents in patients with diabetes type II.

In recent years it was found that the location of glucokinase type such pancreatic beta-cells localized in the rat brain, especially in responsible for nutrition centre (ventromedial hypothalamus; VMH). Long been established that about 20% of neurons in the VMH, called sensitive to glucose by neurons play an important role in the regulation of body weight. The need for food in rats decreases when the brain is injected glucose, whereas inhibition of glucose metabolism by intracerebral introduction analogue of glucose, glucosamine, causes hyperphagia. From the electrophysiological experiments, it was found that sensitive to glucose neuron is activated in response to physiological changes in the concentration of glucose (5-20 mmol), however, its activity is inhibited by inhibition of glucose metabolism using glucosamine. The same mechanism through glucokinase is assumed in the case of sensor systems for the concentration of glucose in VHM, as in the case of insulin secretion in pancreatic beta-cells. Therefore, in addition to action in the liver and pancreatic beta-cells, suggest that activates glucokinase substance in VMH improves the position in relation to the e only sugar levels in the blood, but also obesity, which is a problem a large number of patients with diabetes mellitus type II.

As follows from the above descriptions, activating glucokinase compounds suitable as therapeutic agents and/or prophylactic agents against diabetes mellitus or chronic diabetic complications such as retinopathy, nephropathy, neurosis, ischemic heart disease, or arteriosclerosis, as well as against obesity.

As for compounds with a pyridine skeleton and amide bond attached to the pyridine skeleton, which are contained in the compounds of formula (I) according to the invention, has been described following compound represented by structural formula (IV) (see, for example, the open layout of the patent application of Japan 5-213382).

In the compound of formula (IV)described in the open display patent application Japan 5-213382, however, the position of the C=N and amide linkages in isoxazoline group differs from that of the compounds according to the invention. Also different is the fact that, while the usefulness of the compounds according to the invention include their use against diabetes, usefulness, described in the open display patent application Japan 5-213382, refers to the herbicide.

As for structurally similar to the compounds which are useful against diabetes mellitus, describes the following compounds represented by formula (V):

and formula (VI):

(see, for example, published Japanese International PCT publication 2001-522834).

One of the uses of the compounds described in published Japanese International PCT publication 2001-522834 is used against diabetes, is the same as the use of compounds of formula (I) according to the present invention.

The compound of formula (V) or (VI)described in published Japanese International PCT publication 2001-522834, and the compounds of formula (I) according to the present invention all have the pyridine skeleton as a main skeleton and amide bond with the pyridine cycle.

The difference, however, is that the compounds of formula (I) according to the present invention contain a substituent in position 6 of the pyridine cycle, while the compound of the formula (V) or (VI) has no substituent in position 6 of the pyridine cycle.

In addition, the difference is that the compounds of formula (I) according to the invention are amide bond adjacent to the nitrogen atom, a member of the pyridine cycle, whereas the compound of the formula (VI)described in published Japanese International is native PCT publication 2001-522834, has an amide bond in position, separated by one carbon atom from the nitrogen atom included in the pyridine cycle. In addition, the position of the amide linkages, related to the structural element C=N pyridine cycle corresponding to the cycle In the compounds of formula (I) according to the present invention, differs from that in the case of the compounds of formula (VI) published a translation from the Japanese International PCT publication 2001-522834.

With regard to compounds having the same pyridine-2-carboxamide skeleton, and compounds of formula (I) according to the present invention described compound of formula (VII):

(see, for example, International patent application WO-01/81345). However, the position of the amide bond in relation to the nitrogen atom of 1H-pyrazole[3,4-b]pyridine-4-yl, which is linked to the nitrogen atom of amide bond in the compound of formula (VII), differs from the position of the amide bond in relation to the C=N in the cycle In compounds of formula (I) according to the present invention. In addition, the different is that, while position 3 and 6 of the pyridine skeleton in the formula (VII) are occupied by hydrogen atoms, such compounds of formula (I) are occupied by other groups than hydrogen atoms. Thus, the compound of formula (VI) is different from the compounds of formula (I) according to the present invention throughout the structure.

Therefore, the soybean is inane formula (I) according to the present invention differ from the compounds described in the International patent application WO01/81345 from the point of view of the Deputy-related pyridine skeleton, although both compounds include pyridine-2-carboxamide as the main structure. Thus, the compounds of formula (I) are completely different from the compounds of formula (VII).

The purpose of the invention to provide a therapeutic agent and/or prophylactic agent against diabetes, which can communicate with glucokinase for increasing the activity of glucokinase, and also as a remedy against obesity, which activates glucokinase to stimulate centre of saturation.

As stated above, it is preferable that the compounds according to the invention have better curative effect than existing antidiabetic agents, and provide opportunity to achieve the manifestation of new medicinal effects, which do not have existing antidiabetic agents.

The authors of the present invention, therefore, sought a new anti-diabetic drug that has the best new medicinal effect than existing antidiabetic agents, based on the mechanism of action different from that of existing drugs. As a result, they have found that compounds corresponding to the formula (I)have activating g is urokinase action. Therefore, put in the invention of the goal was achieved.

Disclosure of inventions

Thus, the invention relates to the following:

(1) Compound of formula (I):

[where

X1means N, S or O, or a divalent saturated hydrocarbon group with 1-6 carbon atoms (when the number of carbon atoms of the divalent saturated hydrocarbon group is 2 or more, one of the carbon atoms therein may be replaced by a nitrogen atom, an oxygen atom or a sulfur atom);

R1means 6-10-membered aryl group, a 5-10 membered heteroaryl group, cycloalkyl group having 3-7 carbon atoms or a lower alkyl group (where R1may be substituted by 1 or 2 groups selected from the group consisting of amino, lower alkyl group (the hydrogen atom of the lower alkyl group may be substituted by a group containing a hydroxyl group, a lower alkoxygroup, halogen atom, karbamoilnuyu group, mono - or di(lower alkyl)karbamoilnuyu group, carboxyl group, alkoxycarbonyl group, alkanoyloxy group, amino group, mono - or dialkylamino), low alkoxygroup (the hydrogen atom of methylene or methyl group in the lower alkoxygroup may be substituted by a hydroxyl group, a halogen atom, carbamoyl group is Oh, mono - or di(lower alkyl)carbamoyl group, a carboxyl group, alkoxycarbonyl group, alkanoyloxy group, amino group, mono - or di(lower alkyl)amino group), carbamoyl group, lower alkylcarboxylic group, di(lower alkyl)carbamoyl group, carbamoylating, carbamoyloximes, carboxyl group, ceanography, sulfamoyl group, triptorelin group, halogen atom, hydroxyl group, formyl group, (C2-C6)-alkanoyloxy group, N-(C2-C6-alkanolamines, (C1-C6-allylthiourea, N-(C1-C6)-alkylsulfanyl group, N,N-di(C1-C6)-alkyl)sulfamoyl group, (C1-C6)-alkylsulfanyl group, (C1-C6)-alkylsulfonyl group, N-(C1-C6-alkylsulfonamides, (C1-C6)-alkoxycarbonyl group, N-(C1-C6-alkylamino, N,N-di((C1-C6)-alkyl)amino, 6-10-membered aryl group, and 5-10-membered heteroaryl group);

D is O or S;

R2and R3are the same or different and each means a hydrogen atom, a lower alkyl group, lower alkoxygroup or halogen atom;

formula (II):

means a 5-7 membered heteroaryl group, or 6-1-membered aryl group, which can be in the loop 1 or 2 groups selected from the group consisting of lower alkyl groups, lower alkoxygroup, hydroxyl group, hydroxyalkyl group (the hydrogen atom of the hydroxy-part hydroxyalkyl group, then, may be substituted by a lower alkyl group and halogen atom;

formula (III):

means a monocyclic or bicyclic heteroaryl group in which a carbon atom that is associated with the amide nitrogen atom within the formula (I), forms a C=N together with the nitrogen atom of the cycle (where the heteroaryl group in the case of the cycle may have 1 or 2 substituent selected from the group consisting of lower alkyl groups, lower alkoxygroup, halogen atom, triptorelin group, hydroxyalkyl group (the hydrogen atom of the hydroxy-part hydroxyalkyl group, then, may be substituted by a lower alkyl group), aminoalkyl group (the amino group may be substituted by lower alkyl group), alkanoyloxy group, carboxyl group, alkoxycarbonyl group and cyanopropyl)]

or its pharmaceutically acceptable salt.

(2) Connection on p. (1), where D means S.

(3) the Connection under item (1) or (2), where both R2and R3mean hydrogen atoms.

(4) the Compound according to any one of paragraphs. (1)to(3), where the cycle And means phenyl group, ittia alilou group, imidazolidinyl group, oxazolidinyl group, thiadiazolyl group, thienyl group, triazolyl group, tetrazolyl group, pyridyloxy group, pyrimidinyl group, follow group, thiazolidine group, isoxazolyl group or pyrazolidine group, which may contain in cycle 1 or 2 groups selected from the group consisting of lower alkyl groups, lower alkoxygroup, hydroxy-group, hydroxyalkyl group (the hydrogen atom of the hydroxy-part hydroxyalkyl group, then, may be substituted by a lower alkyl group and halogen atom.

(5) the Compound according to any one of paragraphs. (1)to(4), where X1means a group selected from the group consisting of nitrogen atom, sulfur atom, oxygen atom, -CH2-, -N-CH2-, -S-CH2-, -O-CH2-, -CH2-N-, -CH2-O - and-CH2S.

(6) the Compound according to any one of paragraphs. (1)to(5), where the cycle means a 5 - or 6-membered heteroaryl group which contains at least one nitrogen atom in the structural element C=N, is included in the cycle, as heteroatoms, or 9 - or 10-membered heteroaryl group, which is formed by condensation of the preceding heteroaryl group with phenyl or peredelnoj group.

(7) the Compound according to any one of paragraphs. (1)to(6), where R1means 6-10-membered aryl group, a 5-10 membered heteroaryl group, or cycloalkyl gr is polyurethane foam having 3-7 carbon atoms.

(8) the Compound according to any one of paragraphs. (1)to(6), where R1means 6-10-membered aryl group or a 5-10-membered heteroaryl group.

(9) the Compound according to any one of paragraphs. (1)to(6), where R1means 6-10-membered aryl group.

(10) the Compound according to any one of paragraphs. (1)to(6), where R1means 5-10-membered heteroaryl group.

(11) the Connection under item (9) or (10)where the Deputy in the loop And means a hydrogen atom, a lower alkyl group, lower alkoxygroup, a hydroxyl group or a hydroxy(lower alkyl)-group (the hydrogen atom of the hydroxy-part of the hydroxy(lower alkyl)-group, then, may be substituted by a lower alkyl group).

(12) the Compound according to any one of paragraphs. (9)-(11), where the cycle means thiazolidine group, imidazolidinyl group, isothiazolinone group, thiadiazolyl group, triazolyl group, oxazolidinyl group, isoxazolyl group, personilnya group, pyridyloxy group, pyridazinyl group, pyrazolidine group, pyrimidinyl group, peridocially group or benzothiazolyl group.

(13) the Compound according to any one of paragraphs. (1)to(10), where the substituent in the cycle means a hydrogen atom, a lower alkyl group, halogen atom, hydroxyalkyl group, aminoalkyl group or alkanoyloxy group.

(14) the Compound according to any one of paragraphs. (9)-(12)where the Deputy in R1means a hydrogen atom, hydroxyalkyl is inuu group, lower alkyl group, lower alkoxygroup, karbamoilnuyu group, alkylcarboxylic group, dialkylamino group, cyano, triptorelin group, halogen atom, (C2-C6)-alkanoyloxy group, N-(C2-C6)-alkanolamine, (C1-C6)-alkylsulfonyl group, (C1-C6)-alkylamino or aminoalkyl group.

(15) the Compound according to any one of paragraphs. (1)to(14), where the compound corresponding to the formula (I):

(where the symbols have the same meanings as mentioned above), is:

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-yl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(1-Mei-2-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(1-methyl-1H-tetrazol-5-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(cyclohexylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(thiazol-2-ylsulphonyl)-6-(4H-[,2,4]triazole-3-yl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(2-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-phenylsulfonyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-torpedolike)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(3-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(2,4-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-cyanobenzylidene)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyridine-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-acetylphenylalanine)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(thiophene-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-and sulfanyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(4-methylphenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-chlorophenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(3H-[1,2,4]triazole-4-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methylsulfonylbenzoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-hydroxymethylimidazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methoxymethyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-triftormetilfullerenov)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methylcarbamoylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-yl who sulfanyl)-N-(5-dimethylaminomethylene-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methylsulfinylphenyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-hydroxycyclohexyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridazin-3-yl)-2-pyridinecarboxamide;

3-(pyrazin-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-[4-(1-hydroxyethylaminomethyl)]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(2-methylthiazole-4-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(2-methylthiazole-4-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ilself who yl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(1-methyl-1H-tetrazol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-phenoxy-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(2-chlorophenethylamine)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3,6-bis(pyridine-2-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3,6-bis(4-perpenicular)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3,6-bis(thiazole-2-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3,6-bis(5-methyl[1,3,4]thiadiazole-2-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,3,4]thiadiazole-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylcarbonate-2-yl)-2-feast of dicarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrimidine-4-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridin-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-ethoxycarbonylmethyl-2-yl)-2-pyridinecarboxamide;

3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-phenoxymethyl-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-phenylsulfonyl-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-phenylmethyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-performer)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminocarbonylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminomethylphenol)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-4-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl trocsitalace)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-hydroxyethylthio-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-hydroxy-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methoxycarbonylmethyl-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(pyrimidine-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-hydroxymethyluracil-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(1-methylpyrrolidine-3-yloxy)phenylsulfanyl]-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(1-hydroxy-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-diethylaminoethylcellulose)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-pyrrolidinylcarbonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-Piri is interlocked;

3-(6-dimethylaminoethoxide-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyrazole-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-carbamoyltransferase)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(5-bromo-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethylaminomethyl)]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethylaminomethyl)]-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ILS who lpanel)-N-([1,2,5]thiadiazole-3-yl)-2-pyridinecarboxamide;

3-(2,3-dihydrobenzofuran-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methoxy[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-cyclopropyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(2-herperidin-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(2-methoxypyridine-5-ylsulphonyl)-6-(2H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-diethylcarbamazine)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-cyclopropylamino-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(pyrazole-4-ylsulphonyl)-N-(thiazol-2-is)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminocarbonylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(5-herperidin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(2,3-dihydrobenzofuran-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]triazine-3-yl)-2-pyridinecarboxamide;

3-(4-carboxyphenylazo)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide;

3-(imidazo[1,2-a]pyridine-6-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(2-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[4,5-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(5-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4,4-diftormetilirovaniya)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(feast of the Zin-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-intenlational)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-hydroxyethylidene-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(2-methylimidazo[1,2-a]pyridine-6-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-hydroxymethyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethyl)phenylsulfanyl]-6-(4-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-hydroxy-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(1-methyl-1H-indazol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(3-methyl[1,2,4]triazolo[4,3-a]pyridine-7-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(1-hydroxy-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-hydroxymethyluracil-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-[4-(1H-imidazol-1-yl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4,5-dimethylthiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4,5-dimethyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-[4-(1-methoxyethyl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-hydroxymethylimidazole-2-yl)-2-pyridinecarboxylic the ID;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-cryptomaterial-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-cryptomaterial-2-yl)-2-pyridinecarboxamide;

3-(3-fluoro-4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(1,1-dimethyl-1-hydroxymethyl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(3,4-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(3,5-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]triazolopyrimidine-2-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-oxo-1,6-dihydropyridines-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4-methyl-4H-[1,2,4]-triazole-3-and sulfanyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide.

(16) the Compound which is 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(17) a Compound which is 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(18) a Compound which is 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(19) a Compound which is 3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(20) a Compound which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(21) a Compound which is 3-(hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(22) a Compound which is 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(23) Connect the out, which is 3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(24) a Compound which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(25) a Compound which is 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(26) a Compound which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(27) a Compound which is 3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(28) a Compound which is 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(29) a Compound which is 3-[4-(2-hydroxyethylaminomethyl)]-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-incidencebase or its pharmaceutically acceptable salt.

(30) a Compound which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(31) a Compound which is 3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(32) a Compound which is 3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(33) the Compound which is 3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(34) a Compound which is 3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

(35) the Pharmaceutical composition used for treatment, prevention and/or delay the occurrence of diabetes type II, comprising the following components(1)-(3):

(1) a compound corresponding to the formula (I);

(2) one or more compounds selected from the group consisting of the following components (a)to(g):

another activator glucose the basics;

(b) biguanide;

(C) a PPAR agonist;

(d) insulin;

(e) somatostatin;

(f) inhibitor α-glucosidase and

(g) stimulators of insulin secretion;

and

(3) a pharmaceutically acceptable carrier.

(36) Activates glucokinase agent, which comprises as an effective component the compound according to any one of paragraphs. (1)-(34).

(37) therapeutic and/or prophylactic agent against diabetes, which comprises as an effective component the compound according to any one of paragraphs. (1)-(34).

(38) therapeutic and/or prophylactic agent against obesity, which comprises as an effective component the compound according to any one of paragraphs. (1)-(34).

The best option of carrying out the invention

Listed below are the meanings of the terms used in the present description, for more detailed explanations of the compounds according to the invention.

The term "aryl group" includes aryl groups of cyclic hydrocarbons with 6-14 carbon atoms, such as phenyl group, naftalina group, biphenylene group, antenna group and the like.

The term "lower alkyl group" is preferably meant a linear or branched alkyl group with 1-6 carbon atoms, including, for example, methyl group, ethyl group, through the group, isopropyl group, boutelou GRU is PU, isobutylene group, sec-boutelou group, tert-boutelou group, pentelow group, isoamylene group, neopentylene group, isopentyl group, 1,1-dimethyl-through group, 1-methylbutyl group, 2-methylbutyl group, 1,2-dimethylpropylene group, hexoloy group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1,2,2-trimethylpropyl group, 1-ethyl-2-methylpropyloxy group, and the like.

The term "cycloalkyl group" mean monosilicic saturated hydrocarbon group having 3-7 carbon atoms, including, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group and the like.

The term "lower alkoxygroup" means a group where the hydrogen atom of the hydroxy-group is substituted by the above lower alkyl group, including, for example, a methoxy group, ethoxypropan, propoxylate, isopropoxy, butoxypropyl, sec-butoxypropyl, tert-butoxypropyl, pentyloxy, isopentylamine, hexyloxy, isog is Xylexpo and the like.

The term "alkylsulfonyl group" means a group where the hydrogen atom sulfamoyl group monogamist the above alkyl group, preferably including, for example, methylsulfonyl group, ethylsulfonyl group, isopropylamino group, and the like.

The term "dialkylaminoalkyl group" means a group where the hydrogen atoms of the group NH2alkylsulfonyl group disonesty the same or different above-mentioned alkyl group, including, for example, dimethylsulphamoyl group, diethylcarbamoyl group, methylaminoethanol group and the like.

The term "heteroaryl group" means a 4-7-membered monocyclic heteroaryl group that contains 1-3 heteroatoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, a heteroaryl group, or, alternatively, the bicyclic heteroaryl group, which are formed by condensation of the monocyclic heteroaryl group with the benzene ring or the pyridine cycle, including, for example, follow group, thienyl group, pyrrolidino group, imidazolidinyl group, pyrazolidine group, thiazolidine group, thiadiazolyl group, isothiazolinone group, oxazolidinyl group, isoxazolyl group, pyridyloxy GRU is PU, pyramidalnou group, pyridazinyl group, pyrazolidine group, personilnya group, pinolillo group, izohinolinove group, chinazolinei group, hyalinella group, khinoksalinona group, indolinyl group, benzimidazolyl group, imidazopyridine group, benzofuranyl group, naphthylidine group, 1,2-benzisoxazole group, benzoxazolyl group, benzothiazolyl group, oxazolidinyl group, peridocially group, isothiazolinone group, benzothiazoline group and the like.

The term "halogen atom" includes, for example, fluorine atom, chlorine atom, bromine atom and iodine atom.

The term "lower alkylcarboxylic group" mean karbamoilnuyu group, monosubstituted the above-mentioned lower alkyl group, including, for example, methylcarbamoyl group, ethylcarbitol group, profilirovannuju group, isopropylcarbamate group, butylcarbamoyl group, sec-butylcarbamoyl group, tert-butylcarbamoyl group and the like.

The term "di(lower alkyl)carnemolla group" mean carbamoyl group disubstituted by identical or different above-mentioned alkyl group, including, for example, dimethylcarbamoyl group, diethylcarbamoyl group, ethylmethylamino group is, dipropylamino group, methylpropionamidine group, diisopropylamino group and the like.

The term "lower alkylamino" means an amino group, monosubstituted the above-mentioned lower alkyl group, including, for example, methylaminopropyl, ethylamino, propylamino, isopropylamino, butylamino, sec-butylamino or tert-butylamino.

The term "di(lower alkyl)amino group" means an amino group, a disubstituted by identical or different above-mentioned lower alkyl group, including, for example, dimethylaminopropyl, diethylaminopropyl, dipropylamino, methylpropylamine or diisopropylamino.

The term "alcoolica group" means a carbonyl group to which is connected the above-mentioned lower alkyl group, including, for example, methylcarbamyl group, ethylcarbitol group, propelleronline group, isopropylcarbodiimide group and the like.

The term "alkanolamine" means a group where the above alcoolica group is linked to the amino group, including, for example, medicalbilling, ethylcarboxyl-amino group, isopropylcarbodiimide and the like.

The term "allylthiourea" means a group where the above-mentioned n is SSA alkyl group is linked to the sulfur atom, including, for example, methylthiourea, ethylthiourea, PropertyGroup, isopropylthio and the like.

The term "alkylsulfonyl group" means a group where the above-mentioned lower alkyl group is associated with sulfanilic group, including, for example, methylsulfinyl group, ethylsulfinyl group, isopropylphenyl group and the like.

The term "alkylsulfonyl group" means a group where the above-mentioned alkyl group is associated with sulfonyloxy group, including, for example, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylphenyl group and the like.

The term "alkylsulfonamides" means a group where the hydrogen atom of the amino group monogamist above alkylsulfonyl group, including, for example, methylsulfonylamino, ethylsulfonylimidazo, propylsulfonyl or isopropylbenzylamine.

The term "alkoxycarbonyl group" means a group where the hydrogen atom of the carboxyl group substituted by the above alkyl group, including, for example, methoxycarbonyl group, ethoxycarbonyl group, propylenecarbonate group, isopropoxycarbonyl group and the like.

The term "dvuhvalenten what I saturated hydrocarbon group with 1-6 carbon atoms" means a linear or branched divalent saturated hydrocarbon group with 1-6 carbon atoms, in particular, including, for example, methylene group, ethylene group, propylene group, isopropylene group, butylene group and the like.

For further explanation of specific examples of compounds of formula (I) according to the present invention, the corresponding symbols used in the formula (I), can be explained by the following examples.

Cycle And represented by the formula (II):

[where the respective symbols have the same meanings as above]

means a 5-7 membered heteroaryl group, or 6-10-membered aryl group which may have in a loop And 1 or 2 groups selected from the group consisting of lower alkyl groups, lower alkoxygroup, hydroxyl group, hydroxyalkyl group (the hydrogen atom of the hydroxy-part hydroxyalkyl group, then, may be substituted by a lower alkyl group and halogen atom.

"A 5-7 Membered heteroaryl group, or 6-10-membered aryl group"represented by cycle And is preferably a 5-6-membered heteroaryl group containing at least one nitrogen atom in the cycle.

Cycle And specifically includes, for example, phenyl group, isothiazolinone group, imidazolidinyl group, oxazolidinyl group, thiadiazolyl group, thienyl group, triazolyl group, those who retailnow group, pyridyloxy group, pyrimidinyl group, follow group, thiazolidine group, isoxazolyl group or pyrazolidine group, and preferred is thiazolidine group, imidazolidinyl group, thiazolidine group and Peregrina group, and more preferred, thiazolidine group.

Below explains Deputy associated with the cycle of A.

Cycle And in the formula (I) may have a Deputy or deputies in the loop.

Deputy cycle And includes lower alkyl, alkoxygroup, halogen atom, hydroxy-group and hydroxyalkyl group (the hydrogen atom of the hydroxy-group, then, may be substituted alkyl group). Among these substituents, preferred lower alkyl group, lower alkoxygroup, the hydroxy-group and hydroxyalkyl group, and more preferred is a lower alkyl group.

Deputy in the cycle And, more specifically, includes, for example, methyl group, ethyl group, ISO-propyl group, a methoxy group, ethoxypropan, the hydroxy-group, hydroxymethylene group, hydroxyethylene group, methoxymethyl group, fluorine atom and chlorine atom, preferably a methyl group and ethyl group, and more preferred is methyl group.

Thus, as the preferred cycle And, in General, the preferred groups represented the following formula (VIII):

Group represented by the formula (IX):

are more preferred.

D denotes an oxygen atom or a sulfur atom, of which preferred is a sulfur atom.

The cycle can be explained as follows.

Under the cycle represented by the formula (III):

mean monocyclic or bicyclic heteroaryl group, which is such a relative position as shown in the following formula (X):

in which the structural element C=N cycle is linked to the nitrogen atom of amide groups according to the above-mentioned formula (I).

"Monocyclic or bicyclic heteroaryl group", represented by the cycle has the same value as the above-mentioned "heteroaryl group".

The cycle includes, for example, thiazolidine group, imidazolidinyl group, isothiazolinone group, thiadiazolyl group, triazolyl group, oxazolidinyl group, isoxazolyl group, personilnya group, pyridyloxy group, pyridazinyl group, pyrazolidine group, pyrimidinyl group, peridocially group and benzothiazolyl group. Of these groups preferred thiazolidine group, thiadiazolyl group, isoxazolidine the group, piratininga group, peridocially group and Peregrina group, and more preferred are thiazolidine group, peridocially group and isoxazolidine group.

The cycle can be in the loop 1 or 2 substituent, preferably 1 Deputy selected from the group consisting of lower alkyl groups, lower alkoxygroup, halogen atom, triptorelin group, a hydroxy-group, hydroxyalkyl group (the hydrogen atom of the hydroxy-part of the hydroxyalkyl group may be substituted by a lower alkyl group), aminoalkyl group, alkanoyloxy group, carboxyl group, alkoxycarbonyl group and ceanography.

Of them, as Deputy in the cycle, the preferred lower alkyl group, lower alkoxygroup, halogen atom, hydroxyalkyl group (the hydrogen atom of the hydroxyl part of the hydroxyalkyl group may be substituted by a lower alkyl group), aminoalkyl group and alcoolica group; and more preferred are the lower alkyl group, hydroxyalkyl group (the hydrogen atom of the hydroxy-part of the hydroxyalkyl group may be substituted by a lower alkyl group) and alcoolica group.

Deputy cycle In specifically includes, for example, methyl group, ethyl group, through the group, isopropyl group, boutelou group, me is oxygraph, ethoxypropan, propoxylate, isopropoxy, butoxypropyl, chlorine atom, fluorine atom, bromine atom, hydroxymethylene group, hydroxyethylene group, methoxymethyl group, ethoxyethylene group, methoxyamino group, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, aminomethyl group, aminoethyl group, aminopropyl group, methylcarbamyl group, ethylcarbitol group, propelleronline group, and the like. Of them preferred a methyl group, an ethyl group, a chlorine atom, a fluorine atom, hydroxymethylene group, hydroxyethylene group, methoxymethyl group, ethoxyethylene group, methoxycarbonyl group, ethoxycarbonyl group, aminomethyl group, aminoaniline group, methylcarbamyl group and acylcarnitine group; and more preferred are a methyl group, hydroxymethylene group, methoxymethyl group and methylcarbamyl group.

Therefore, as a cycle, in General, preferred, for example, thiazole-2-ilen group, 4-methylthiazole-2-ilen group, 4-hydroxymethylimidazole-2-ilen group, 4-methoxycarbonylmethyl-2-ilen group, 4-methoxymethanol-2-ilen group, 4-aminomethylphenol-2-ilen group, 4-cenotesa-2-ilen group, 4-cortisol-2-ilen group, imidazol-2-ilen GRU is PA, 4-Mei-2-ilen group, 4-methoxycarbonylamino-2-ilen group, isothiazol-3-ilen group, 4-hydroxymethylimidazole-3-ilen group, a [1,3,4]-thiadiazole-2-ilen group, 5-methylcarbamyl[1,3,4]thiadiazole-2-ilen group, [1,2,4]thiadiazole-5-ilen group, 3-methyl[1,2,4]thiadiazole-5-ilen group, [1,2,4]triazole-2-ilen group, 5-hydroxymethyl[1,2,4]triazole-3-strong group, pyrazin-2-ilen group, pyridine-2-ilen group, 4-methylpyridin-2-ilen group, 4-ethoxymethyleneamino-2-ilen group, 4-methylcarbamoylmethyl-2-ilen group, 5-hydroxymethylimidazole-2-ilen group, 5-methyl[1,3,4]thiadiazole-2-ilen group, 5-fluoro[1,3,4]thiadiazole-2-ilen group, 5-methyl[1,2,4]triazole-2-ilen group, 5-methylcarbamyl[1,2,4]triazole-3-ilen group, isoxazol-3-ilen group, 4-methoxymethylethoxy-2-ilen group, 5-methylisoxazol-3-ilen group, 5-hydroxymethylimidazole-3-ilen group, 5-methoxymethylethoxy-3-ilen group, 5-methylcarbonate-3-ilen group, 5-chlorzoxazone-3-ilen group, 5-aminomethylation-3-ilen group, 4-methyl-1H-pyrazole-3-ilen group, 1-methylpyrazole-3-ilen group, 6-methylpyridazin-3-ilen group, thiazol-4-ilen group, 2-methylthiazole-4-ilen group, isoxazol-3-ilen group, peridocially group and the like.

X1means a nitrogen atom, a sulfur atom or an oxygen atom, or a divalent saturated coal is a hydrogen group with 1-6 carbon atoms.

Under the "divalent saturated hydrocarbon group with 1-6 carbon atoms" means alkylenes group with 1-6 carbon atoms as specified above, including, for example, methylene group, a propylene group, isopropylene group, butylene group and the like. If the number of carbon atoms of the divalent saturated hydrocarbon group is 2 to 6, optionally a carbon atom in the divalent saturated hydrocarbon group may be replaced by a nitrogen atom, a sulfur atom or an oxygen atom.

X1includes, more specifically, for example, nitrogen atom, oxygen atom, sulfur atom, -CH2-, -N-CH2-, -S-CH2-, -O-CH2-, -CH2-N-, -CH2-S -, and-CH2-O-, and the like. Of them preferred nitrogen atom, a sulfur atom, an oxygen atom, -N-CH2- and-CH2-, and more preferred is a sulfur atom.

R2and R3are the same or different and each means a hydrogen atom, a lower alkyl group, alkoxygroup or halogen atom.

"Lower alkyl group"denoted by the radicals R2and R3are the same or different, each preferably means methyl or ethyl group; more preferably, both of the radical R2and R3means methyl group.

"The lower alkoxygroup, designated for Alami R 2and R3are the same or different, each preferably means methoxy - or ethoxypropan; more preferably, both of the radical R2and R3means a methoxy group.

The "halogen atom", denoted by the radicals R2and R3preferably is a fluorine atom, a chlorine atom or a bromine atom, of which more preferred is a fluorine atom or a chlorine atom.

As for R2and R3both R2and R3preferably are hydrogen atoms.

R1means 6-10-membered aryl group, a 5-10 membered heteroaryl group, cycloalkyl group having 3-7 carbon atoms or a lower alkyl group.

"6-10-membered aryl group, denoted by R1means aryl hydrocarbon group cycle with 6-10 carbon atoms or a 9 - or 10-membered bicyclic aryl group formed by condensation of benzene cycle with a 5 - or 6-membered aliphatic heterocycle (aliphatic heterocycle may be substituted by actigraphy), including in this case 1 or 2 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

6-10-Membered aryl group, a hydrocarbon cycle, more specifically, includes, for example, phenyl group, naftalina group, biphenylene group and the like, of which predpochtitel the Noi is a phenyl group.

9 - or 10-Membered bicyclic aryl group, more specifically, includes, for example, ethylenedioxythiophene group, methylenedioxyphenyl group, tetrahydropyranyloxy group, tetrahydroisoquinoline group, dihydroindolone group, 2,3-dihydrobenzofuranyl group, 1,3-dihydrotes-fornillo group, oxyindole group or isoindolyl group and the like, of which the preferred is ethylenedioxythiophene group or tetrahydroisoquinoline group.

Under "5-10-membered heteroaryl group, denoted by R1assume 5-7-membered monocyclic heteroaryl group or a 9 - or 10-membered bicyclic heteroaryl group, which in this case contains 1-3 heteroatoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom.

5-7-Membered monocyclic heteroaryl group, more specifically, includes, for example, isoxazolyl group, isothiazolinone group, imidazolidinyl group, oxazolidinyl group, thiazolidine group, thiadiazolyl group, thienyl group, triazolyl group, tetrazolyl group, pyridyloxy group, personilnya group, pyrimidinyl group, pyridazinyl group, pyrazolidine group, pyrrolidino group, pyranyloxy group, follow group, foratenolol group, imide is solidarily group and the like.

9 - or 10-membered bicyclic heteroaryl group, more specifically, includes, for example, izohinolinove group, isoindolyl group, indolenine group, pinolillo group, peridocially group, benzoimidazolyl group, benzoxazolyl group, benzothiazolyl group, benzotriazolyl group, benzofuranyl group, imidazolidinyl group, triazapentadiene group and the like.

As for the 5-10-membered heteroaryl group, preferably a 5-7 membered monocyclic heteroaryl group, more specifically, the preferred Peregrina group, imidazolidinyl group, thiazolidine group or thienyl group.

"Cycloalkyl group having 3-7 carbon atoms", denoted by R1includes the same groups as those mentioned above, and particularly preferred is cyclopentenone group or tsiklogeksilnogo group.

"Lower alkyl group", denoted by R1includes the same groups as mentioned above; particularly preferred through the group and bucilina group.

As for R1preferred 6-10-membered aryl group, a 5-10 membered heteroaryl group, a 3-7-membered cycloalkyl group, and more preferred, 6-10-membered aryl group, a 5-10 membered heteroaryl group.

Specific examples include phenyl, y is the SCP, naftalina group, biphenylene group, isoxazolyl group, isothiazolinone group, imidazolidinyl group, oxazolidinyl group, thiazolidine group, thiadiazolyl group, thienyl group, triazolyl group, tetrazolyl group, pyridyloxy group, personilnya group, pyrimidinyl group, pyridazinyl group, pyrazolidine group, pyrrolidino group, pyranyloxy group, follow group, foratenolol group, imidazolidinyl group, izohinolinove group, isoindolyl group, indolenine group, ethylenedioxythiophene group, methylenedioxyphenyl group, pinolillo group, peridocially group, dihydroindolone group, tetrahydropyranyloxy group, tetrahydroisoquinoline group, benzoimidazolyl group, benzoxazolyl group, benzothiazolyl group, benzotriazolyl group, benzofuranyl group, cyclopropyl group, cyclobutyl group, cyclopentyloxy group, tsiklogeksilnogo group, cycloheptyl group, methyl group, ethyl group, through the group, isopropyl group, boutelou group, pentelow group, and the like. Of them, preferred phenyl group, naftalina group, Peregrina group, imidazolidinyl group, thiazolidine group, thienyl group, cyclopentenone group and collage the strong group; and more preferred are a phenyl group, Peregrina group, imidazolidinyl group, thiazolidine group and thienyl group, of which particularly preferred phenyl group or Peregrina group.

The following context is illustrated by the Deputy is contained in the radical R1.

The Deputy is contained in the radical R1includes a hydrogen atom, amino group, hydroxyl group, hydroxyalkyl group (the hydrogen atom of the hydroxyl group may be substituted by a lower alkyl group), a lower alkyl group (the hydrogen atom of the lower alkyl group may be substituted by a hydroxyl group, alkoxygroup, amino group, alkylamino, dialkylamino, a halogen atom, carbamoyl group, mono - or dialkylanilines group, a carboxyl group, alkoxycarbonyl group or alkanoyloxy group), a lower alkoxygroup (the hydrogen atom of the methylene group or a methyl group contained in the lowest alkoxygroup may be substituted by a hydroxyl group, a halogen atom, carbamoyl group, mono- or di(lower alkyl)carbamoyl group, a carboxyl group, alkoxycarbonyl group or alkanoyloxy group), karbamoilnuyu group, alkylcarboxylic group, dialkylamino group, carbamoyloximes, carbamoylation the group, the cyano, sulfamoyl group, triptorelin group, halogen atom, formyl, (C2-C6)-alkanoyloxy group, N-(C2-C6)-alkanolamine, (C1-C6)-allylthiourea, N-(C1-C6)-alkylsulfanyl group, N,N-di-(C1-C6)-alkylsulfanyl group, (C1-C6)-alkylsulfanyl group, (C1-C6)-alkylsulfonyl group, N-(C1-C6)-alkylsulfonamides, (C1-C6)-alkoxycarbonyl group, (C1-C6)-alkylamino and N,N-(C1-C6)-dialkylamino.

R1may contain hydroxyalkyl group as a substituent. Preferred hydroxyalkyl group includes, for example, hydroxymethylene group, hydroxyethylene group, hydroxypropyl group, hydroxyisopropyl group, hydroxybutyl group, hydroxypethidine group, and the like, and more preferred are hydroxymethylene group, hydroxyethylene group, hydroxiproline group or hydroxyisopropyl group.

The hydrogen atom of the hydroxyl group may be substituted by a lower alkyl group with 1-6 carbon atoms. Substituted hydroxyalkyl group includes, for example, methoxymethyl group, 1-methoxyamino group, ethoxymethyl group, metox the ethyl group, propylhexedrine group and the like. Which one is preferable methoxymethyl group or ethoxyethylene group, and more preferred is methoxymethyl group.

R1may contain lower alkyl group as a substituent. The specified lower alkyl group include the same groups as mentioned above; of these, preferred methyl group, ethyl group, through the group, bucilina group, isopropyl group and the like, and more preferred is methyl group or ethyl group.

When R1contains lower alkyl group as a substituent, a hydrogen atom of the lower alkyl group may be substituted by a hydroxyl group, a lower alkoxygroup, amino group, monoalkylamines or dialkylamines. The lower alkyl group includes, for example, hydroxymethylene group, hydroxyethylene group, methoxymethyl group, ethoxymethyl group, methoxyamino group, aminomethyl group, aminoethyl group, aminopropyl group, methylaminomethyl group, ethylaminomethyl group, dimethylaminomethyl group, ethylmethylamino group, aminomethyl group, 2-aminoethyl group, 1-aminoethyl group, 3-aminopropyl group, 2-amino-1-methylamino group, 2-aminopropylene the group, 4-aminobutyl group, 2-amino-1-methylpropyl group, 2-aminobutyl group, 5-aminopentyl group, 3-amino-1,2-dimethylpropylene group, 6-aminohexyl group and the like. Which one is preferable aminomethyl group, 2-aminoaniline group, 1-aminoaniline group, 3-aminopropyl group, 3-amino-1-mtilatila group and 2-aminopropyl group, and more preferred is 2-aminoaniline group or 3-aminopropylene group.

R1may contain lower alkoxygroup (where one of the hydrogen atoms of the lower alkoxygroup may be substituted by a hydroxy-group or amino group) as Deputy.

Alkoxygroup includes the same groups as mentioned above; of these, preferred methoxy group, ethoxypropan, propoxylate, isopropoxy and the like, and more preferred is a methoxy group or ethoxypropan.

When the hydrogen atom of alkoxygroup substituted hydroxyl group, it includes, for example, 2-hydroxy-ethoxypropan, 3-hydroxypropoxy, 4-hydroxyethoxy group, 2-hydroxy-1-methylethoxy, 2-hydroxypropoxy, 3-hydroxy-2-methylpropoxy, 3-hydroxybutyrate, and the like; of these, preferred 2-hydroxyethoxy, 3-hydroxypropoxy and 2-hydroxy-1-methylethoxy, and more prefer Inoi is 2-hydroxyethoxy.

When the hydrogen atom of alkoxygroup substituted amino group, the amino group, then, may be substituted by 1 or 2 lower alkyl groups. When the amino group substituted 2 lower alkyl groups, the alkyl groups may be the same or different; such substituted alkoxygroup includes, preferably, acylaminoalkyl or dialkylaminoalkyl, and, more preferably, dialkylaminoalkyl.

More specifically, for example, you can call aminoethoxy, methylaminoacetaldehyde, dimethylaminoethoxy, dimethylaminopropoxy, and the like. Of them preferred methylaminomethyl or dimethylaminoethoxide, and more preferred is dimethylaminoethoxide.

R1may contain lower alkylcarboxylic group as a substituent. Lower alkylcarboxylic group includes the same groups as those mentioned above, preferably, the lower alkylcarboxylic group with 1-5 carbon atoms, more preferably, lower alkylcarboxylic group with 1-3 carbon atoms. Preferred lower alkylcarboxylic group, specifically, includes methylcarbamoyl group, ethylcarbitol group, profilirovannuju group and the like, and more preferred is methylcarbamoyl group.

R1may win a di(lower alkyl)karbamoilnuyu group as a substituent. Lower alkylcarboxylic group includes the same groups as those mentioned above, and, for example, dimethylcarbamoyl group, diethylcarbamoyl group, ethylmethylamino group and the like, and more preferred is dimethylcarbamoyl group.

R1may contain a halogen atom as a substituent. The halogen atom include the same halogen atoms as mentioned above, for example, fluorine atom, chlorine atom, bromine atom, and the like, and preferred is a fluorine atom or a chlorine atom.

R1may contain (C2-C6)-alkanoyloxy group as a substituent. (C2-C6)-Alcoolica group includes the same groups as those mentioned above, more specifically, for example, methylcarbamyl group, ethylcarbitol group, propelleronline group or isopropylcarbodiimide group, and more preferred is methylcarbamyl group or acylcarnitine group.

R1may contain N-(C2-C6)-alkanolamine as Deputy. Preferred N-(C2-C6-alkanolamines, specifically, includes, preferably, for example, ethylcarbodiimide, propylnitrosamine, isopropylcarbodiimide, and the like, and more preferred is methylcobalamine the group or ethylcarbodiimide.

R1may contain (C1-C6)-allylthiourea as Deputy. Allylthiourea includes the same groups as those listed above. Preferred allylthiourea, specifically, includes, preferably, for example, methylthiourea, ethylthiourea, PropertyGroup, isopropylthio, and the like, and more preferable is methylthiourea or ethylthiourea.

R1may contain alkylsulfonyl group as a substituent. Alkylsulfonyl group includes the same groups as those listed above. Preferred alkylsulfonyl group includes, preferably, for example, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, and the like, and more preferred is methylsulfonyl group or ethylsulfonyl group.

R1may contain dialkylaminoalkyl group as a substituent. Dialkylaminoalkyl group includes the same groups as those listed above. Preferred dialkylaminoalkyl group, specifically, includes, for example, dimethylsulphamoyl group, diethylcarbamoyl group, and the like, and more preferred is dimethylsulphamoyl group.

R1may contain alkylsulfonyl group as replaces the La. Alkylsulfonyl group includes the same groups as those listed above. Preferred alkylsulfonyl group, specifically, includes, for example, methylsulfinyl group, ethylsulfinyl group, propylsulfonyl group, isopropylphenyl group, and the like, and more preferred is methylsulfinyl group or ethylsulfinyl group.

R1may contain alkylsulfonyl group as a substituent. Alkylsulfonyl group includes the same groups as those listed above. Preferred alkylsulfonyl group, specifically, includes, for example, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylphenyl group, and the like, and more preferred is methylsulfonyl group or ethylsulfonyl group.

R1may contain alkylsulfonamides as Deputy. Alkylsulfonamides includes the same groups as those listed above. Preferred alkylsulfonamides, specifically, includes, for example, methylsulfonylamino, ethylsulfonylimidazo, propylsulfonyl, isopropylbenzylamine, and the like, and more preferable is methylsulfonylamino or ethylsulfonyl the A.

R1may contain alkoxycarbonyl group as a substituent. Alkoxycarbonyl group includes the same groups as those listed above. Preferred alkoxycarbonyl group, specifically, includes, for example, methoxycarbonyl group, ethoxycarbonyl group, isopropoxycarbonyl group, propoxycarbonyl group, and the like, and more preferred is methoxycarbonyl group or ethoxycarbonyl group.

R1may contain alkylamino as Deputy. Alkylamino includes the same groups as those listed above. Preferred alkylamines, specifically, includes, for example, methylaminopropyl, ethylamino, and the like, and more preferable is methylaminopropyl.

R1may contain N,N-di((C1-C6)-alkyl)amino group as a substituent. Preferred N,N-di((C1-C6)-alkyl)amino group includes, for example, dimethylaminopropyl, diethylaminopropyl, ethylmethylamino, and the like, and more preferable is dimethylaminopropyl.

R1can contain 5 - or 6-membered cyclic amino group as a substituent. 5 - or 6-membered cyclic amino group include the same groups as the above as the "cyclic is aminogruppy". Preferred "Deputy contained in R1"that includes, for example, pyrrolidinyl group, piperazinilnom group, morpholinyl group, and the like, and more preferred is piperidinyl group or morpholinyl group.

In relation to substituents at R1preferred is a hydrogen atom, a lower alkyl group, lower alkoxygroup, carnemolla group, alkylcarboxylic group, cyano, triptorelin group, halogen atom, (C2-C6)-alcoolica group, N-(C2-C6-alkanolamine, (C1-C6)-alkylsulfonyl group, (C1-C6-alkylamino or aminoalkyl group, and more preferred is a lower alkyl group, lower alkoxygroup, alkylcarboxylic group, halogen atom, (C1-C6)-alkylsulfonyl group or aminoalkyl group.

Consequently, the relatively-X1-R1more specifically, the preferred groups are phenylsulfanyl group, 4-hydroxyethylpyrrolidine group, 3-hydroxymethanesulfinic group, 2-hydroxymethanesulfinic group, 4-methylphenylsulfonyl group, 3-methylphenylsulfonyl group, 2-methylphenylsulfonyl group, 4-isopropylbenzenesulfonyl group, 4-methoxy who animalfunny group, 4-ethoxymethylenemalonic group, 3-methoxyphenylalanine group, 2-ethoxybenzonitrile group, 4-ethoxyphenylurea group, 4-hydroxymethanesulfinic group, 4-gidroksietilirovaniya group, 4-carbamoyltransferase group, 4-methylcarbamoylmethyl group, 4-dimethylcyclohexylamine group, 4-isopropylcyclopentadienyl group, 4-cyanobenzylidene group, 4-triftormetilfullerenov group, 4-fortunaltely group, 3-chlorophenylsulfonyl group, 2-fortunaltely group, 4-methylcarbamoylmethyl group, 4-etilbromizovalerta group, 3-methylcarbamoylmethyl group, 3-etilkarbitola group, 4-methylcarbamoylmethyl group, 4-etilkarbitola group, 4-isopropylbenzenesulfonyl group, 4-methylsulfinylphenyl group, 3-arilsulfonilglitsiny group, 4-methylsulfinylphenyl group, 4-isopropylbenzenesulfonyl group, 4-methylaminoacetaldehyde group, 3-ethylaminoethanol group, 2-methylaminoacetaldehyde group, 4-aminomethanesulfonic group, 3-aminomethylpyrrolidine group, 4-aminoethylaminomethyl the th group, 4-dimethylaminoethylmethacrylate group, a thiazol-2-ylsulphonyl group, 4-hydroxymethylimidazole-2-ilen group, 5-hydroxymethylimidazole-2-ylsulphonyl group, 4-hydroxyethylthio-2-ylsulphonyl group, 4-methylthiazole-2-ylsulphonyl group, 5-methylthiazole-2-ylsulphonyl group, 4-utiltity-2-ylsulphonyl group, 4-methoxythiazole-2-ylsulphonyl group, 4-toxicity-2-ylsulphonyl group, 4-carbamoylmethyl-2-ylsulphonyl group, 5-carbamoylmethyl-2-ylsulphonyl group, 4-methylcarbamoylmethyl-2-ylsulphonyl group, 4-ethylcarbamate-2-ylsulphonyl group, 4-isopropylthiazole-2-ylsulphonyl group, 4-cenotesa-2-ylsulphonyl group, 4-chlorothiazole-2-ylsulphonyl group, 4-cortisol-2-ylsulphonyl group, 4-methylcarbonate-2-ylsulphonyl group, 4-ethylcarbonate-2-ylsulphonyl group, 4-ethylcarbodiimide-2-ylsulphonyl group, 4-methylcarbamoylmethyl-2-ylsulphonyl group, 4-methylsulfonylmethyl-2-ylsulphonyl group, 4-ethylsulfonyl-2-ylsulphonyl group, 3-methylsulfonylmethyl-2-ylsulphonyl group, 4-isopropylthiazole-2-ylsulphonyl group, 4-methylaminomethyl-2-ylsulphonyl group, 3-methylaminomethyl-2-ylsulphonyl group, 4-ethylaminomethyl-2-ylsulphonyl group, 4-aminomethylation the l-2-ylsulphonyl group, 4-aminotriazole-2-ylsulphonyl group, pyridine-2-ylsulphonyl group, pyridine-3-ylsulphonyl group, pyridine-4-ylsulphonyl group, 6-hydroxymethyluracil-3-ylsulphonyl group, 4-hydroxymethylpropane-5-ylsulphonyl group, 4-hydroxymethylpropane-6-ylsulphonyl group, 3-hydroxymethylpropane-6-ylsulphonyl group, 4-methylpyridin-5-ylsulphonyl group, 4-methylpyridin-6-ylsulphonyl group, 6-methylpyridin-3-ylsulphonyl group, 6-methoxypyridine-3-ylsulphonyl group, 6-ethoxypyridine-3-ylsulphonyl group, 2-carbamoylation-4-ylsulphonyl group, 6-carbamoylation-3-ylsulphonyl group, 6-methylcarbamoylmethyl-3-ylsulphonyl group, 2-methylcarbamoylmethyl-4-ylsulphonyl group, 2-cyano-4-ylsulphonyl group, 6-cyano-3-ylsulphonyl group, 2-triptorelin-4-ylsulphonyl group, 6-triptorelin-3-ylsulphonyl group, 2-chloropyridin-4-ylsulphonyl group, 6-chloropyridin-3-ylsulphonyl group 2-herperidin-4-ylsulphonyl group, 6-herperidin-3-ylsulphonyl group, 2-methylcarbonate-4-ylsulphonyl group, 6-methylcarbonate-3-ylsulphonyl group, 2-ethylcarbodiimide-4-ylsulphonyl group, 6-ethylcarbodiimide-3-ylsulphonyl group, 2-methylsulfinylphenyl-4-ylsulphonyl gr is the PAP 6-methylsulfonylmethyl-3-ylsulphonyl group, 2-ethylsulfonyl-4-ylsulphonyl group, 6-isopropylacetanilide-3-ylsulphonyl group, 2-methylcarbamoylmethyl-4-ylsulphonyl group, 6-methylcarbamoylmethyl-3-ylsulphonyl group, 2-methylaminomethyl-4-ylsulphonyl group, 6-methylaminomethyl-3-ylsulphonyl group, 2-ethylaminomethyl-4-ylsulphonyl group, 6-ethylaminomethyl-3-ylsulphonyl group, 2-aminomethylpyridine-4-ylsulphonyl group, 6-aminomethylpyridine-3-ylsulphonyl group 4-gidroksidifenilaminom, 3-hydroxymethylamino, 2-hydroxymethylamino, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 4-ethylenediaminetetra, 4-isopropylbenzylamine, 4-methoxybenzylamine, 3-methoxybenzylamine, 2-ethoxyphenylurea, 4-ethoxyphenylurea, 4-hydroxymethylamino, 4-carbamoylating, 4-methylcarbamoylmethyl, 4-isopropylcarbodiimide, 4-cyanoaniline, 4-triftormetilfullerenov, 4-pertanyaannya, 3-chlorpheniramine, 2-pertanyaannya, 4-methylcarbaniloyloxy, 4-ethylcarbodiimide, 3-methylcarbaniloyloxy, 3-ethylcarbodiimide, 4-methylcarbaniloyloxy is, 4-etilbromizovalerta, 4-isopropylbenzylamine, 4-methylsulfonylamino, 3-arilsulfonilglitsinov, 4-isopropylbenzylamine, 4-methylenedianiline, 3-ethylenediaminetetra, 4-aminomethylenemalonate, 3-aminomethylenemalonate, 4-aminoethylethanolamine, 3-aminoethylethanolamine, 4-methylthiazole-2-luminograph, 5-methylthiazole-2-luminograph, 4-utiltity-2-luminograph, 5-utiltity-2-luminograph, 4-toxicity-2-luminograph, 5-methoxythiazole-2-luminograph, 4-carbamoylmethyl-2-luminograph, 5-carbamoylmethyl-2-luminograph, 4-methylcarbamoylmethyl-2-luminograph, 4-ethylcarbamate-2-luminograph, 4-methylthiazole-2-luminograph, 4-cenotesa-2-luminograph, 4-chlorothiazole-2-luminograph, 4-cortisol-2-luminograph, 4-ethylcarbamate-2-luminograph, 4-isopropylthiazole-2-luminograph, 4-methylcarbonate-2-luminograph, 4-ethylcarbonate-2-luminograph, 4-ethylcarbodiimide-2-luminograph, 4-methylcarbamoylmethyl-2-luminograph, 4-methylsulfonylmethyl-2-luminograph, 4-ethylsulfonyl-2-luminograph, 3-methylsulfonylmethyl-2-luminograph, 4-isopropylthiazole-2-luminograph, 4-methylaminomethyl-2-luminograph, 3-methylaminomethyl-2-luminograph, 4-ethylaminomethyl-2-Il, who kinogruppa, 4-aminomethylphenol-2-luminograph, 4-aminotriazole-2-luminograph, 3-aminomethylphenol-2-luminograph, pyridine-4-luminograph, 6-hydroxymethyluracil-3-luminograph, 3-hydroxymethylpropane-4-luminograph, 4-hydroxymethylpropane-2-luminograph, 5-hydroxymethyluracil-2-luminograph, 3-methylpyridin-4-ylsulphonyl group, 4-methylpyridin-2-luminograph, 6-methylpyridin-3-luminograph, 6-methoxypyridine-3-luminograph, 2-carbamoylation-4-luminograph, 6-carbamoylation-3-luminograph, 6-methylcarbamoylmethyl-3-luminograph, 2-methylcarbamoylmethyl-4-luminograph, 2-cyano-4-luminograph, 6-cyano-3-luminograph, 2-triptorelin-4-luminograph, 6-triptorelin-3-luminograph, 2-chloropyridin-4-luminograph, 6-chloropyridin-3-luminograph, 2-herperidin-4-luminograph, 6-herperidin-3-luminograph, 2-methylcarbonate-4-luminograph, 6-methylcarbonate-3-luminograph, 2-ethylcarbodiimide-4-luminograph, 6-ethylcarbodiimide-3-luminograph, 2-methylsulfinylphenyl-4-luminograph, 6-methylsulfonylmethyl-3-luminograph, 2-ethylsulfonyl-4-luminograph, 6-isopropylacetanilide-3-luminograph, 2-methylcarbamoylmethyl-4-luminograph, 6-methylcarbamoylmethyl-3-luminograph, 2-methylaminomethyl-4-luminograph, 6-methylaminopropyl-raminagrobis, 2-ethylaminomethyl-4-luminograph, 6-ethylaminomethyl-3-luminograph, 2-aminomethylpyridine-4-luminograph, 6-aminomethylpyridine-3-luminograph, 4-hydroxymethylbenzene, 4-hydroxyethylbenzene, 3-hydroxymethylbenzene, 3-hydroxyethylmethacrylate, 4-methylphenoxy, 3-ethylenoxide, 4-methoxyphenoxy, 3-methoxyphenoxy, 4-ethoxyphenoxy, 4-carbamoylphenoxy, 3-carbamoylphenoxy, 4-methylcarbamoylmethyl, 3-isopropylcarbonate, 4-cyanoprokaryota, 3-cyanoprokaryota, 4-triftormetilfosfinov, 3-triftormetilfosfinov, 4-chlorphenoxy, 3-chlorphenoxy, 4-perfekcyjna, 3-perfekcyjna, 4-methylcarbonylbuthoxy, 3-methylcarbonylbuthoxy, 4-ethylcarboxylate, 4-methylcarbaniloyloxy, 3-methylcarbaniloyloxy, 4-methylsulfinylphenyl, 3-methylsulfinylphenyl, 4-arilsulfonilglitsinov, 3-arilsulfonilglitsinov, 4-metilaminofenazon, 3-metilaminofenazon, 4-ethyleneoxide, 3-ethyleneoxide, 4-aminomethylenemalonate, 3-aminomethylenemalonate, 4-aminoethylethanolamine, 3-aminoethylethanolamine, 4-gidroksidifenilaminom, 3-hydroxymethylnicotinamide, 2-hydroxymethylnicotinamide, 4-methylphe the ylmethylamino, 3-methylphenylethylamine, 2-methylphenylethylamine, 4-ethylphenethylamine, 4-isopropylbenzylamine, 4-methoxyphenylethylamine, 3-methoxyphenylethylamine, 2-ethoxytrimethylsilane, 4-ethoxymethyleneamino, 4-hydroxymethylnicotinamide, 4-carbamoylating, 4-methylcarbamoylmethyl, 4-isopropylcyclopentadienyl, 4-cyanophenylacetic, 4-triftormetilfullerenov, 4-performancerating, 3-chlorophenylalanine, 2-chlorophenylalanine, 2-performancerating, 4-methylcarbamoylmethyl, 4-ethylcarbodiimide, 3-methylcarbamoylmethyl, 3-ethylcarbodiimide, 4-methylcarbamoylmethyl, 4-ethicalvolunteering.org, 4-isopropylcyclopentadienyl, 4-methylsulfonylmethane, 3-arilsulfonilglitsinov, 4-isopropyltriphenylphosphonium, 4-methylaminoanthraquinone, 3-acylaminopenicillins, 4-aminomethylenemalonate, 3-aminomethylpyrrolidine, 4-aminoethylethanolamine, 3-aminoethylethanolamine, 4-methylthiazole-2-ylmethylamino, 5-methylthiazole-2-ylmethylamino, 4-this is thiazol-2-ylmethylamino, 5-utiltity-2-ylmethylamino, 4-toxicity-2-ylmethylamino, 5-methoxythiazole-2-ylmethylamino, 4-carbamoylmethyl-2-ylmethylamino, 5-carbamoylmethyl-2-ylmethylamino, 4-methylcarbamoylmethyl-2-ylmethylamino, 4-ethylcarbamate-2-ylmethylamino, 4-methylthiazole-2-ylmethylamino, 4-cenotesa-2-ylmethylamino, 4-chlorothiazole-2-ylmethylamino, 4-cortisol-2-ylmethylamino, 4-methylcarbamoylmethyl-2-ylmethylamino, 4-ethylcarbamate-2-ylmethylamino, 4-isopropylthiazole-2-ylmethylamino, 4-methylcarbonate-2-ylmethylamino, 4-ethylcarbonate-2-ylmethylamino, 4-ethylcarbodiimide-2-ylmethylamino, 4-methylcarbamoylmethyl-2-ylmethylamino, 4-methylsulfonylmethyl-2-ylmethylamino, 4-ethylsulfonyl-2-ylmethylamino, 3-methylsulfonylmethyl-2-ylmethylamino, 4-isopropylthiazole-2-ylmethylamino, 4-methylaminomethyl-2-ylmethylamino, 3-methylaminomethyl-2-ylmethylamino, 4-ethylaminomethyl-2-ylmethylamino, 4-aminomethylphenol-2-ylmethylamino, 4-aminotriazole-2-ylmethylamino, 3-aminomethylphenol-2-ylmethylamino, pyridine-4-ylmethylamino, 6-hydroxymethyluracil-3-ylmethylamino, 3-hydroxymethylpropane-4-ylmethylamino, 4-hydroxymethylpropane-2-ilma is luminograph, 5-hydroxymethyluracil-2-ylmethylamino, 3-methylpyridin-4-ylsulphonyl group, 4-methylpyridin-2-ylmethylamino, 6-methylpyridin-3-ylmethylamino, 6-methoxypyridine-3-ylmethylamino, 2-carbamoylation-4-ylmethylamino, 6-carbamoylation-3-ylmethylamino, 6-methylcarbamoylmethyl-3-ylmethylamino, 2-methylcarbamoylmethyl-4-ylmethylamino, 2-cyano-4-ylmethylamino, 6-cyano-3-ylmethylamino, 2-triptorelin-4-ylmethylamino, 6-triptorelin-3-ylmethylamino, 2-chloropyridin-4-ylmethylamino, 6-chloropyridin-3-ylmethylamino, 2-herperidin-4-ylmethylamino, 6-herperidin-3-ylmethylamino, 2-methylcarbonate-4-ylmethylamino, 6-methylcarbonate-3-ylmethylamino, 2-ethylcarbodiimide-4-ylmethylamino, 6-ethylcarbodiimide-3-ylmethylamino, 2-methylsulfinylphenyl-4-ylmethylamino, 6-methylsulfonylmethyl-3-ylmethylamino, 2-ethylsulfonyl-4-ylmethylamino, 6-isopropylacetanilide-3-ylmethylamino 2-methylcarbamoylmethyl-4-ylmethylamino, 6-methylcarbamoylmethyl-3-ylmethylamino, 2-methylaminomethyl-4-ylmethylamino, 6-methylaminomethyl-3-luminograph, 2-ethylaminomethyl-4-luminograph, 6-ethylaminomethyl-3-luminograph, 2-aminomethyl the DIN-4-luminograph, 6-aminomethylpyridine-3-ylmethylamino, 3-hydroxyethylpyrrolidine group, 2-hydroxyethylpyrrolidine group, 4-methylphenylethyl group, 3-methylphenylethyl group, 2-methylphenylethyl group, 4-isopropylbenzylamine group, 4-methoxyphenylacetylene group, 3-methoxyphenylethylamine group, 2-ethoxyphenylurea group, 4-ethoxyphenylurea group, 4-hydroxyethylpyrrolidine group, 4-carbamoylmethyl group, 4-methylcarbamoylmethyl group, 4-isopropylcyclopentadienyl group, 4-cyanopyrrolidine group, 4-triftormetilfullerenov group, 4-performatively group, 3-chlorpheniramine group, 2-performatrin group, 4-methylcarbamoylmethyl group, 4-ethylcarbodiimide group, 3-methylcarbamoylmethyl group, 3-ethylcarbodiimide group, 4-methylcarbamoylmethyl group, 4-ethylcarbodiimide group, 4-isopropylcyclopentadienyl group, 4-methylsulfonylmethyl group, 3-arilsulfonilglitsiny group, 4-isopropylcyclopentadienyl group, 4-methylaminophenol group, 3-ethylenediaminetetra group, 2-methylaminophenol group, 4-aminomethylpyrrolidine group, 3-aminomethylpyrrolidine group, 4-aminoethylethanolamine group, a thiazol-2-ylmethyl the Naya group, 4-hydroxymethylimidazole-2-ilen group, 5-hydroxymethylimidazole-2-ylmethylene group, 4-hydroxyethylthio-2-ylmethylene group, 4-methylthiazole-2-ylmethylene group, 5-methylthiazole-2-ylmethylene group, 4-utiltity-2-ylmethylene group, 4-methoxythiazole-2-ylmethylene group, 4-toxicity-2-ylmethylene group, 4-carbamoylmethyl-2-ylmethylene group, 5-carbamoylmethyl-2-ylmethylene group, 4-methylcarbamoylmethyl-2-ylmethylene group 4-ethylcarbamate-2-ylmethylene group, 4-isopropylthiazole-2-ylmethylene group, 4-cenotesa-2-ylmethylene group, 4-chlorothiazole-2-ylmethylene group, 4-cortisol-2-ylmethylene group, 4-methylcarbonate-2-ylmethylene group, 4-ethylcarbonate-2-ylmethylene group, 4-ethylcarbodiimide-2-ylmethylene group, 4-methylcarbamoylmethyl-2-ylmethylene group, 4-methylsulfonylmethyl-2-ylmethylene group, 4-ethylsulfonyl-2-ylmethylene group, 3-methylsulfonylmethan-2-ylmethylene group, 4-isopropylthiazole-2-ylmethylene group, 4-methylaminomethyl-2-ylmethylene group, 3-methylaminomethyl-2-ylmethylene group, 4-ethylaminomethyl-2-ylmethylene group, 4-aminomethylphenol-2-ylmethylene group, 4-aminotriazole-2-ylmethylene group, pyridine-4-ylmethylene group, 6-hydroxymethyluracil-3-ylmethylene group, 3-hydroxymethylpropane-4-ylmethylene group, 4-hydroxymethyl is iridin-2-ylmethylene group, 3-methylpyridin-4-ylsulphonyl group, 4-methylpyridin-2-ylmethylene group, 6-methylpyridin-3-ylmethylene group, 6-methoxypyridine-3-ylmethylene group, 2-carbamoylation-4-ylmethylene group, 6-carbamoylation-3-ylmethylene group, 6-methylcarbamoylmethyl-3-ylmethylene group, 2-methylcarbamoylmethyl-4-ylmethylene group, 2-cyano-4-ylmethylene group, 6-cyano-3-ylmethylene group, 2-triptorelin-4-ylmethylene group 6-triptorelin-3-ylmethylene group, 2-chloropyridin-4-ylmethylene group, 6-chloropyridin-3-ylmethylene group, 2-herperidin-4-ylmethylene group, 6-herperidin-3-ylmethylene group, 2-methylcarbonate-4-ylmethylene group, 6-methylcarbonate-3-ylmethylene group, 2-ethylcarbodiimide-4-ylmethylene group, 6-ethylcarbodiimide-3-ylmethylene group, 2-methylsulfinylphenyl-4-ylmethylene group, 6-methylsulfonylmethyl-3-ylmethylene group, 2-ethylsulfonyl-4-ylmethylene group, 6-isopropylacetanilide-3-ylmethylene group, 2-methylcarbamoylmethyl-4-ylmethylene group, 6-methylcarbamoylmethyl-3-ylmethylene group, 2-methylaminomethyl-4-ylmethylene group, 6-methylaminomethyl-3-luminograph, 2-ethylaminomethyl-4-luminograph, 2-ethylaminomethyl-5-luminograph, 2-aminomethylpyridine-4-luminograph, 6-aminomethylpyridine-3-ylmethylene group is and. Of these preferred groups are phenylsulfanyl group, 4-hydroxyethylpyrrolidine group, 4-methylphenylsulfonyl group, 3-methylphenylsulfonyl group, 4-methoxyphenylalanine group, 3-methoxyphenylalanine group, 4-ethoxyphenylurea group, 4-hydroxymethanesulfinic group, 4-hydroxyethanesulfonic group, 4-carbamoyltransferase group, 4-methylcarbamoylmethyl group, 4-dimethylcyclohexylamine group, 4-cyanobenzylidene group, 4-triftormetilfullerenov group, 4-fortunaltely group, 3-chlorophenylsulfonyl group, 2-fortunaltely group, 4-methylcarbamoylmethyl group, 4-etilkarbitola group, 4-methylcarbamoylmethyl group, 4-methylsulfinylphenyl group, 4-methylaminoacetaldehyde group, 4-aminomethanesulfonic group, 4-aminoethylethanolamine group, 4-dimethylaminoethylmethacrylate group, a thiazol-2-ylsulphonyl group, 4-methylthiazole-2-ylsulphonyl group, 5-methylthiazole-2-ylsulphonyl group, pyridine-4-ylsulphonyl group, pyridine-3-ylsulphonyl group, pyridine-2-ylsulphonyl group, 6-hydroxymethyluracil-3-ylsulphonyl group, 6-methylpyridin-3-ILS is levanella group, 6-methoxypyridine-3-ylsulphonyl group, 6-carbamoylation-3-ylsulphonyl group, 6-methylcarbamoylmethyl-3-ylsulphonyl group, 2-cyano-4-ylsulphonyl group, 6-cyano-3-ylsulphonyl group, 6-triptorelin-3-ylsulphonyl group, 2-chloropyridin-4-ylsulphonyl group, 6-chloropyridin-3-ylsulphonyl group, 2-herperidin-4-ylsulphonyl group, 6-herperidin-3-ylsulphonyl group, 6-methylcarbonate-3-ylsulphonyl group 6-ethylcarbodiimide-3-ylsulphonyl group, 6-methylsulfonylmethyl-3-ylsulphonyl group, 6-methylcarbamoylmethyl-3-ylsulphonyl group, 6-methylaminomethyl-3-ylsulphonyl group, 6-ethylaminomethyl-3-ylsulphonyl group, 6-aminomethylpyridine-3-ylsulphonyl group, 4-methylpentylamino, 4-methoxybenzylamine, 4-pertanyaannya, 4-methylthiazole-2-luminograph, 5-methylthiazole-2-luminograph, pyridine-4-luminograph, 2-methylpyridin-5-luminograph, 4-methylphenoxy, 4-methoxyphenoxy, 4-perfekcyjna, 4-Methylpheniltiomethyl group, 3-Methylpheniltiomethyl group, 2-Methylpheniltiomethyl group, 4-tortenelmietlen group, 2-chlorophenylalanine, 2-tortenelmietlen group, 4-methylthiazole-2-luminometry group, 5-methylthiazole-2-luminometry group, the feast of the DIN-4-luminometry group, 6-methylpyridin-3-luminometry group, 2-methylpyridin-5-luminometry group, 4-methylphenylethyl group, 4-methoxyphenylacetylene group and 4-performatively group; more preferred groups are phenylsulfanyl group, 4-hydroxyethylpyrrolidine group, 4-methylphenylsulfonyl group, 3-methylphenylsulfonyl group, 4-methoxyphenylalanine group, 3-methoxyphenylalanine group, 4-ethoxyphenylurea group, 4-hydroxymethanesulfinic group, gidroksietilirovaniya group, 4-carbamoyltransferase group, 4-methylcarbamoylmethyl group, 4-dimethylcyclohexylamine group, 4-cyanobenzylidene group, 4-triftormetilfullerenov group, 4-fortunaltely group, 3-chlorophenylsulfonyl group, 2-fortunaltely group, 4-methylcarbamoylmethyl group, 4-methylsulfinylphenyl group, 4-dimethylaminoethylmethacrylate group, pyridine-4-ylsulphonyl group, pyridine-3-ylsulphonyl group, 6-methoxypyridine-3-ylsulphonyl group, 6-methylpyridin-3-ylsulphonyl group and 6-triptorelin-3-ylsulphonyl group; and even more preferred groups are phenylsulfanyl group, 4-hydroxyethylaminophenol the group, 4-methylphenylsulfonyl group, 4-methoxyphenylalanine group, 4-ethoxytrimethylsilane group, 4-methylcarbamoylmethyl group, 4-dimethylcyclohexylamine group, 4-cyanobenzylidene group, 4-triftormetilfullerenov group, 4-fortunaltely group, 2-fortunaltely group, 4-methylcarbamoylmethyl group, 4-methylsulfinylphenyl group, 4-dimethylaminoethylmethacrylate group, pyridine-4-ylsulphonyl group, pyridine-3-ylsulphonyl group, 6-methoxy-4-ylsulphonyl group, 6-methoxypyridine-3-ylsulphonyl group and 6-methylpyridin-3-ylsulphonyl group.

As indicated above, the compounds according to the invention corresponding to the formula (I):

(where the symbols have the same meanings as above)

more specifically include, for example,

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-yl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(1-Mei-2-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-forfei sulfanyl)-6-(1-methyl-1H-tetrazol-5-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(cyclohexylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(thiazol-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-yl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(2-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-phenylsulfonyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-torpedolike)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(3-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(2,4-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-cyanobenzylidene)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyridine-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-label inititiate-2-yl)-2-pyridinecarboxamide;

3-(4-acetylphenylalanine)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(thiophene-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(4-methylphenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-chlorophenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(3H-[1,2,4]triazole-4-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methylsulfonylbenzoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-hydroxymethylimidazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methoxymethyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-triftormetilfullerenov)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(TIA the ol-2-yl)-2-pyridinecarboxamide;

3-(4-methylcarbamoylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-dimethylaminomethylene-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methylsulfinylphenyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-hydroxycyclohexyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridazin-3-yl)-2-pyridinecarboxamide;

3-(pyrazin-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-[4-(1-hydroxyethylaminomethyl)]-6-(4H-[1,2,4]triazole-3-ILS who lpanel)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(2-methylthiazole-4-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(2-methylthiazole-4-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(1-methyl-1H-tetrazol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-phenoxy-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(2-chlorophenethylamine)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3,6-bis(pyridine-2-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3,6-bis(4-perpenicular)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3,6-bis(thiazole-2-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3,6-bis(5-methyl[1,3,4]thiadiazole-2-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(doing Sasol-3-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,3,4]thiadiazole-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylcarbonate-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrimidine-4-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridin-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-ethoxycarbonylmethyl-2-yl)-2-pyridinecarboxamide;

3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-phenoxymethyl-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-phenylsulfonyl-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-phenylmethyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-performer)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimetilan nautillienellidae)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminomethylphenol)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-4-yl)-2-pyridinecarboxamide;

3-(4-dimethylallyltranstransferase)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-hydroxyethylthio-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-hydroxy-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methoxycarbonylmethyl-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(pyrimidine-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-hydroxymethyluracil-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(1-methylpyrrolidine-3-yloxy)phenylsulfanyl]-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridin Roxane;

3-(1-hydroxy-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-diethylaminoethylcellulose)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-pyrrolidinylcarbonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-dimethylaminoethoxide-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyrazole-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2 pyridinecarboxamide;

3-(4-carbamoyltransferase)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(5-bromo-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethylaminomethyl)]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethylaminomethyl)]-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,5]thiadiazole-3-yl)-2-pyridinecarboxamide;

3-(2,3-dihydrobenzofuran-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methoxy[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-cyclopropyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(2-herperidin-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(2-methoxypyridine-5-ylsulphonyl)-6-(2H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-diethylcarbamazine-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-cyclopropylamino-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(pyrazole-4-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminocarbonylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(5-herperidin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(2,3-dihydrobenzofuran-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]triazine-3-yl)-2-pyridinecarboxamide;

3-(4-carboxyphenylazo)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide;

3-(imidazo[1,2-a]pyridine-6-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(2-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinyl is the oksamid;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[4,5-b]pyridine-2-yl)-2-pyridinecarboxamide;

3-(5-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4,4-diftormetilirovaniya)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-intenlational)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-hydroxyethylidene-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(2-methylimidazo[1,2-a]pyridine-6-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-hydroxymethyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethyl)phenylsulfanyl]-6-(4-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(5-hydroxy-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(1-methyl-1H-indazol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(3-methyl[1,2,4]Tria is olo[4,3-a]pyridine-7-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(1-hydroxy-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-hydroxymethyluracil-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-[4-(1H-imidazol-1-yl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4,5-dimethylthiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4,5-dimethyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxime thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(1-methoxyethyl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-hydroxymethylimidazole-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-cryptomaterial-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-cryptomaterial-2-yl)-2-pyridinecarboxamide;

3-(3-fluoro-4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-[4-(1,1-dimethyl-1-hydroxymethyl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(3,4-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(3,5-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]triazolopyrimidine-2-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-oxo-1,6-dihydropyridines-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(1-methyl-1H-[12]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide. Of these preferred compounds are 3-(4-perpenicular)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(pyridine-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-chlorophenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(3H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxide ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,3,4]thiadiazole-2-yl)-2-pyridinecarboxamide;

3-(4-methylsulfonylbenzoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-hydroxymethylimidazole-2-yl)-2-pyridinecarboxamide;

3-(4-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-N,N-dimethylaminoethylacrylate)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-alsultany the)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-2-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethyl)phenylsulfanyl]-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ilal the Anil)-N-(pyridin-2-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide; or 3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide. More preferred examples include 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-N,N-dimethylaminoethylacrylate)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide;

3-(4-meth is kmimetypefinder)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-2-yl)-2-pyridinecarboxamide;

3-[4-(2-hydroxyethylaminomethyl)]-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide;

3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide;

3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide; and

3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide.

Derivatives of 2-pyridinecarboxamide according to the present invention can also be in the form of pharmaceutically acceptable salts, including additive salt and acid additive salts of the bases.

In some cases, the compounds according to the present invention are in the form of stereoisomers or tautomers, such as optical isomers, diastereomers and geometric isomers, depending on the position of the substituents. All of these isomers, of course, are within the scope of the present invention. In addition, the scope of the present invention also includes mixtures of these isomers in any proportion.

Compounds according to the present invention possess activity against activation of glucokinase and therefore they are suitable as a therapeutic and/or prophylactic agents against diabetes, as well as against diabetic complications.

Under diabetic complication mean disease caused by the development of diabetes, and include, for example the EP, diabetic nephropathy, diabetic retinopathy, diabetic neurosis, diabetic arteriosclerosis and so on.

Compounds according to the present invention is applicable as in the case of insulin-dependent diabetes mellitus (IDDM)and non-insulin dependent diabetes mellitus (NIDDM).

Believe that insulin-dependent diabetes mellitus (IDDM) is due to the increase of insulin resistance caused by obesity, in addition to genetic predisposition in reducing insulin secretion and insulin resistance, primarily in skeletal muscle in adults. Insulin-dependent diabetes mellitus was proposed to be divided into type I and type II, depending on the predisposition.

Suppose that the compounds according to the present invention is effective not only in the case of insulin-dependent diabetes type I, but also in diabetes type II, in which used still antidiabetic drugs are unable to sufficiently reduce the level of sugar in the blood.

In the case of diabetes mellitus type II, the blood sugar level after eating significantly maintained at a high level for a long period of time compared with that of healthy people. Compounds according to the present invention is suitable against this type II diabetes.

Below is illustrated the method of obtaining the compounds according to the present invention.

The compounds of formula (I) according to the present invention can be easily obtained in accordance with the well-known reactionary way or in itself can be known. The compounds of formula (I) according to the invention can be obtained by the conventional method, carried out in the liquid phase, or a newly developed solid-phase method, such as a combined synthetic method or the parallel method of synthesis. Preferably, they can be obtained, for example, according to the following methods.

(where the symbols have the same meanings as above).

Stage 1

At this stage, derived dichloropyridazine acid or its reactive derivative is introduced into the reaction aminoguanidinium (2)to give compound (3). The reaction can be carried out by using the reaction leading to the formation of amide previously described method (for example, Basic Principle and Experiments in Peptide Syntheses, Nobuo Izumiya, etc., Maruzen Co., Ltd., 1983; Comprehensive Organic Synthesis, 6, Pergamon Press, 1991), a corresponding method, or a combination of them and the standard ways. That is, the reaction is carried out in the presence of a condensing means known to the person skilled in the art, or such act is trained, as a way to activation of ester, the method using a mixed acid anhydride, a method using a carboxylic acid or a way with carbodiimide, which can be used by the person skilled in the art. This agent leading to the formation of amide includes, for example, thionyl chloride, oxalicacid, N,N-dicyclohexylcarbodiimide, 1-methyl-2-bromo-pyridiniumyl, N,N'-carbonyldiimidazole, diphenylphosphoryl, diphenylphosphoryl, N,N'-disuccinimidyl, N,N'-disuccinimidyl, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, ethylchloride, isobutylparaben or benzotriazol-1-yloxytris(dimethylamino)fosfodiesterasa. Of these agents are preferred, for example, thionyl chloride, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N,N-dicyclohexylcarbodiimide or benzotriazol-1-yloxytris(dimethylamino)fosfodiesterasa. In the case of reactions leading to the formation of amide, a base and an auxiliary agent for condensation can be used together with leading to the formation of amide agent.

Used the base includes, for example, tertiary aliphatic amines, such as trimethylamine, triethylamine, N,N-diisopropylethylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, N,N-dimethylaniline, 1,8-diazabicyclo[5,4,0]-undec-7-ene (DBU) or 1,5-asobi is yclo[4,3,0]non-5-ene (DBN); and aromatic amines such as pyridine, 4-dimethylaminopyridine, picoline, lutidine, quinoline or isoquinoline. Of them preferred tertiary aliphatic amines, especially triethylamine or N,N-diisopropylethylamine.

Used auxiliary agent for the condensation include, for example, N-hydroxybenzotriazole, N-hydroxysuccinic-imide, N-hydroxy-5-norbornene-2,3-dicarboxamide or 3-hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazol. Which one is preferable, for example, N-hydroxybenzotriazole, and the like.

The compound (2) may be used usually in an amount of 0.1-10 equivalents, preferably 0.5 to 3 equivalents, per 1 equivalent of the carboxylic acid derivative (1) or its reactive derivative, however, this number depends on the type of compound and solvent and other reaction conditions.

Leading to the formation of amide agent may be used in quantities of 1-10 equivalents, preferably 1-3 equivalents, per 1 equivalent of the carboxylic acid derivative (1) or its reactive derivative, however, this number depends on the type of compound and solvent and other reaction conditions.

Auxiliary agent for condensation may be used usually in an amount of 1-10 equivalents, preferably 1-3 equivalents, per 1 equivalent of the carboxylic acid derivative (1) or R is actionresponse derivative, however, this number depends on the type of compound and solvent and other reaction conditions.

The base can be used usually in an amount of 1-10 equivalents, preferably 1-5 equivalents, however, this number depends on the type of compound and solvent and other reaction conditions.

There are no particular restrictions on the solvent for the reaction, is used at this stage if it does not adversely affect the reaction; such a solvent includes, for example, an inert solvent, in particular dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, ethyl acetate, methyl acetate, acetonitrile, benzene, xylene, toluene, 1,4-dioxane, tetrahydrofuran, dimethoxyethane or their mixture. Whereas the maintenance of an appropriate reaction temperature, preferred is dichloromethane, chloroform, 1,2-dichloroethane, acetonitrile or N,N-dimethylformamide.

The reaction temperature at this stage can usually be a temperature from -78°C to the boiling temperature under reflux of the solvent, preferably from 0°With 30°C.

The reaction time at this stage can usually be from 0.5 hours to 96 hours, preferably from 3 hours to 24 hours.

Base, leading to the formation of amide agent and auxiliary agent for condensation used this with the adiya's, can be used individually or in combination of 2 or more types.

When the compound (3)obtained at this stage, contains a protective group in the substituent in the cycle, the protective group, if necessary, can be removed. The removal of the protective group can be carried out as described previously (Protective Groups in Organic Synthesis, T.W. Green, 2nd edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard methods.

Thus obtained compound (3) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, crystallization, solvent extraction, the resultant deposition rates, chromatography, and so forth. Alternatively, the compound (3) can be used at a later stage without purification.

Stage 2

At this stage, obtained in stage 1 connection (3) is injected into the reaction with compound (4), corresponding to the formula R1X1H (X1means an oxygen atom, a nitrogen atom or a sulfur atom; R1has the same meanings as above), or a compound of the formula (II):

receiving a connection (5), (6) or (I-1).

The compound (4)used in this reaction, is a derivative of phenol, derived thiol or amine derivative. Derived phenol includes such, in which the hydroxyl group is linked to the aryl group, and such, in which the hydroxyl group is linked to a 5-7-membered heteroaryl group.

At this stage, when used as a compound (4)can be obtained compound (5).

By reaction with a compound corresponding to the formula (5) (where the symbols have the same meanings as mentioned above), the compound of the formula (II-1) is a derivative of phenol or thiol derivative, in which the group-DH (where D denotes an oxygen atom or a sulfur atom) is linked to the cycle And the compounds of formula (II) (where the derivative of the phenol has the same meaning as above).

At this stage, when used as a compound of the formula (II)can be obtained compound (6) or (I-1).

At this stage, the compound (4) or (II) may be used usually in an amount of 0.2 to 10 equivalents, preferably 1-3 equivalents, per 1 equivalent of compound (3).

The compound (I-1) is included in the compounds of formula (I) according to the invention.

The base is used at this stage include, for example, tertiary aliphatic amines, such as trimethylamine, triethylamine, N,N-diisopropylethylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, N,N-dimethylaniline, 1,8-diazabicyclo[5,4,0]-undec-7-ene (DBU) or 1,5-azabicyclo[4,3,0]non-5-ene (DBN); aromatic amines such as pyridine, 4-dimethylaminopyridine, picoline, lutidine, quinoline or isoquinoline; alkali metals, that is s as potassium, sodium or lithium; hydrides of alkali metals, such as sodium hydride or potassium hydride; ORGANOMETALLIC compounds such as utility; alkali metal alcoholate, such as tert-butyl potassium, sodium ethylate or sodium methylate; hydroxides of alkali metals such as potassium hydroxide or sodium hydroxide; carbonates of alkali metals such as potassium carbonate, sodium carbonate or cesium carbonate. One of them is particularly preferred tertiary aliphatic amines, hydrides of alkali metals, carbonates of alkali metals or alkali metal alcoholate, and especially triethylamine or N,N-diisopropylethylamine, sodium hydride or potassium carbonate, or alkali metal alcoholate, such as tert-butyl potassium, sodium ethylate or sodium methylate.

The base is used at this stage, can be generally used in amounts of 0.2 to 10 equivalents, preferably 1-5 equivalents, per 1 equivalent of compound (3), however, this number depends on the type of compound and solvent used.

There are no special restrictions on solvent used for the reaction, if it does not adversely affect the reaction; such a solvent includes, for example, inert organic solvents. Specifically, it includes, for example, dichloromethane, chloroform, 1,2-dichloroethane, trichloroethane, N,N-DIMET formamid, N,N-dimethylacetamide, N-organic, acetone, ethanol, isopropanol, tert-butanol, tert-amyl alcohol, ethyl acetate, methyl acetate, acetonitrile, benzene, xylene, toluene, 1,4-dioxane, tetrahydrofuran, dimethoxyethane or their mixture. Of them, preferred are N,N-dimethylformamide, N,N-dimethylacetamide, N-organic, acetonitrile, isopropanol and tert-amyl alcohol, and more preferred N,N-dimethylformamide, acetonitrile or isopropanol.

The reaction time is usually from 0.2 hour to 100 hours, preferably from 1 hour to 40 hours.

The reaction temperature is usually from -20°C to the boiling temperature under reflux solvent used, preferably from 0°C to the boiling temperature under reflux of the solvent.

At this stage, the reaction can be performed as described previously (Organic Letters, 4, No. 20, 3517-3520 (2002)), a corresponding method, or a combination of them and the standard ways. If necessary, the reaction medium can be added to the catalyst and the additive.

As for the catalyst used at this stage, there may be used any type of catalyst for accelerating the reaction, including, for example, copper chloride, copper bromide, copper iodide, copper oxide, copper acetate, and the like, and more preferred is copper iodide.

As for the additives used at this stage, it can be used any type of additive that accelerates the reaction, including, for example, ethylene glycol, dimethoxyethane, and the like, and more preferred is ethylene glycol.

Thus obtained compound (5) or (6) may be isolated and purified in the usual way, for example, by concentration, vacuum distillation, the resultant deposition rates, solvent extraction, crystallization, chromatography and so on. Alternatively, the compound (5) or (6) can be used at a later stage without purification.

The compound (I-1) according to the present invention can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, the resultant deposition rates, solvent extraction, crystallization, chromatography and so on.

(where the symbols have the same meanings as above)

Stage 3-1

At this stage, the compound (5)obtained in stage 2, is introduced into reaction with a derivative of phenol or thiazole, including cycle And formula (II):

(where the symbols have the same meanings as mentioned above) in the presence of a base, obtaining the compound (I-2) according to the invention.

At this stage, the reaction can be carried out in the same manner as in stage 2, provided the use is of the same solvent for the reaction, the reaction time and the reaction temperature and the same number of equivalents of the parent compounds.

Thus obtained compound (I-2) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (I-2) can be used at a later stage without purification.

Stage 3-2

At this stage, the compound (6)obtained in stage 2, is introduced into reaction with the compound (4), corresponding to the formula R1X1H (where the symbols have the same meanings as above)to give compound (I-3).

At this stage, the reaction can be carried out in the same manner as in stage 2, using the same solvent for the reaction, the reaction time and the reaction temperature and the same number of equivalents of the parent compounds and bases.

Thus obtained compound (I-3) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, crystallization, solvent extraction, the resultant deposition rates, chromatography, and so forth. Alternatively, the compound (I-3) can be used at a later stage without purification.

The compound (I-4) according to the invention can also be perceived by the s according to the following method:

(where W stands for a protective group for carboxyl, and other symbols have the same meanings as above).

Stage 4

At this stage, a carboxyl group derived dichloropyridine-2-carboxylic acid (1) to introduce a protective group, receiving the connection (11). The compound (11) can be obtained in a known manner or by appropriate method. There are no special restrictions with regard to the protective group W for the carboxyl group in the compound (11), if it is used as a protective group for carboxyl group at stages 5 and 6 and can be easily removed at the stage 7. Such protective group includes, for example, linear or branched lower alkyl groups such as methyl group, ethyl group and tert-bucilina group; halogenated lower alkyl groups such as 2-iodates and 2,2,2-trichloroethyl; lower alkeneamine groups such as allyl group, 2-protanilla group and 2-methyl-2-protanilla group; and kalkilya groups such as benzyl group and RPS-group.

Introduction and removal of the protective group W in the case of a carboxyl group can be carried out in the way described earlier (Protective Groups in Organic Synthesis, T.W. Green, 2nd edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard methods.

Thus obtained the the group of (11) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, the resultant deposition rates, crystallization, chromatography, and so forth. Alternatively, the compound (11) can be used at a later stage without purification.

Stage 5

At this stage, the compound (11)obtained in stage 4, is introduced into reaction with compound (12), corresponding to the formula R1X1H (where the symbols have the same meanings as above)to give compound (13).

At this stage, the reaction can be carried out in the same manner as in the case of stage 2, using the same solvent for the reaction, the reaction time and the reaction temperature and the same number of equivalents of the parent compounds and bases.

Thus obtained compound (13) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (13) can be used at a later stage without purification.

Stage 6

At this stage, the compound (13)obtained in stage 5, is introduced into reaction with a derivative of phenol or thiazole, corresponding to the formula (II):

(where the symbols have the same meanings as specified in the above), receiving a connection (15).

Compound (15) are obtained by introducing into a reaction derivative of phenol or a derivative of the thiol. In the case of the reaction of a derivative of phenol has the same values as above.

At this stage, the reaction can be carried out in the same manner as in stage 2, using the same reaction time, reaction temperature and solvent for the reaction and the same number of equivalents of the parent compounds and the same number of grounds.

Thus obtained compound (15) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, the resultant deposition rates, solvent extraction, crystallization, chromatography, and so forth. Alternatively, the compound (15) can be used at a later stage without purification.

Stage 7

At this stage, from the compound (15)obtained in stage 6, remove the protective group W for carboxyl, receiving the connection (16).

The removal of the protective group W in the case of a carboxyl group at this stage can be carried out as described previously (Protective Groups in Organic Synthesis, T.W. Green, 2-e edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard methods.

Thus obtained compound (16) can be isolated and purified in the usual way, for example, by the oxygen is compete, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, compound (16) can be used at a later stage without purification.

Stage 8

At this stage, carboxylic acid derivative (16), obtained in stage 7, is introduced into reaction with the compound (2)to give compound (I-4) according to the invention.

The reaction used in this stage is the so-called leading to amide formation reaction, which can be carried out in the same manner as in stage 1, using the same reaction temperature and reaction time, reaction temperature and the same number of equivalents of the parent compounds and the same amount of the condensing agent and an auxiliary agent.

Thus obtained compound (I-4) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (I-4) can be used at a later stage without purification.

The compound (I-5) according to the present invention can also be obtained according to the following method:

(where W1means a protective group for a thiol; X2means delete the controls group; and other symbols have the same meanings as above).

Stage 9

At this stage, from compound (19) remove the protective group for a thiol, receiving a connection (20).

The removal of the protective group in the case Tilney group at this stage can be carried out as described previously (Protective Groups in Organic Synthesis, T.W. Green, 2-e edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard methods.

As for the protective group W1for thiol, can be used in any type of group, if this group can be easily removed at this stage by getting the SH group. Such protective group W1the thiol includes, for example, acyl groups such as acetyl group or benzoline group, or substituted kalkilya groups, such as triticina group or 4-methoxyaniline group.

Thus obtained compound (20) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, compound (20) can be used at a later stage without purification.

Stage 10

At this stage, the compound (20)obtained in stage 9, is introduced into reaction with the compound (21) in the presence of a base, receiving the connection (22).

As for soy is inane (21), used at this stage, there may be used any type of connection, if X2in the compound (21) is removed by the group, leading to the compounds (22). As X2use, for example, halogen atom such as fluorine atom, chlorine atom, bromine atom or iodine atom or a sulfonate or phosphonate, and preferred is a fluorine atom, chlorine atom, iodine atom or triftorbyenzola, and more preferred is a fluorine atom, a chlorine atom or iodine atom.

At this stage, the reaction can be carried out in the same manner as in stage 2, using the same reaction time, number of initial connections and grounds.

Thus obtained compound (22) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, crystallization, solvent extraction, the resultant deposition rates, chromatography, and so forth. Alternatively, the compound (22) can be used at a later stage without purification.

Stage 11

At this stage, the compound (22)obtained in stage 10, is introduced into reaction with compound (8) in the presence of a base, obtaining the compound (I-5).

At this stage, the reaction can be carried out in the same manner as in stage 2, using the same reaction time, reaction temperature and solvent of Gleneagle and the same number of source connections and grounds.

Thus obtained compound (I-5) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, crystallization, solvent extraction, the resultant deposition rates, chromatography, and so forth.

Of the compounds according to the invention, when X1-R1in the formula (I) means-CH2-O-R1or-CH2-S-R1the compound (I-6) according to the present invention can be obtained in the following way.

(where the symbols have the same meanings as above).

Stage 12

At this stage, a derivative of cyano (25) is injected into the reaction with m-chloroperoxybenzoic acid (mCPBA)to give compound (26). The oxidation reaction at this stage can be carried out as described previously (Tetrahedron, 42, No. 5, 1475-1485), a corresponding method, or a combination of them and the standard ways. mCPBA can be used usually in amounts of 0.5 to 1 equivalent, preferably 1-3 equivalents, per 1 equivalent of compound (25).

The reaction can be carried out in a period of time from 10 minutes to 24 hours, preferably from 30 minutes to 12 hours at a temperature of from -20°C to the boiling point of the solvent, preferably from 0°C to the boiling point of the solvent.

As for the solvent for the reaction may be is used any type of solvents, if it has no adverse effect on the reaction, including, for example, chloroform, dichloromethane, 1,2-dichloroethane, and the like.

Thus obtained compound (26) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (26) can be used at a later stage without purification.

Stage 13

At this stage, the compound (26)obtained in stage (12), is introduced into reaction with POCl3receiving the connection (27).

Used in this reaction POCl3can be used usually in amounts of 0.5 to 100 equivalents, preferably 1 to 20 equivalents, per 1 equivalent of compound (26).

The reaction can be carried out usually at a temperature of from -20°C to the boiling point of the solvent, preferably from 20°C to the boiling point of the solvent. The reaction time is usually from 0.5 hour up to 50 hours, preferably from 1 hour to 24 hours.

As solvent for the reaction can be used any type of solvent, if it has no adverse effect on the reaction, preferably includes, for example, dichloromethane, chloroform, dichloroethane, acetonitrile, N,N-dimethylformamide, and the like that is. Thus obtained compound (27) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, the resultant deposition rates, crystallization, chromatography, and so forth. Alternatively, the compound (27) can be used at a later stage without purification.

Stage 14

At this stage, the compound (27)obtained in stage 13, is introduced into reaction with compound (12)obtained in stage 5, in the presence of a base, receiving the connection (28).

At this stage, the reaction can be carried out in the same manner as in stage 5, when using the same reaction temperature, reaction time and the same amount of starting compound (12) and the base.

Thus obtained compound (28) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, compound (28) can be used at a later stage without purification.

Stage 15

At this stage, the compound (28)obtained in stage 14, is introduced into reaction with the compound (14), obtaining the compound (29).

The reaction at this stage can be carried out in the same manner as in stage 2, using the same reaction temperature, time reacts is and solvent for the reaction and the same number of source connections and grounds.

Thus obtained compound (29) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (29) can be used at a later stage without purification.

Stage 16

At this stage, the compound (29), obtained in stage 15, hydrolyzing to obtain carboxylic acid (30). Hydrolysis at this stage is carried out using an alkali. As for the alkali, there can be used any type of alkali with which the cyano compound (29) is transformed into carboxyl group; this includes alkali, preferably aqueous solution of sodium hydroxide, potassium hydroxide, barium hydroxide, lithium hydroxide, and the like, and more preferred is an aqueous solution of sodium hydroxide or potassium hydroxide.

The alkali may be used usually in amounts of 1-100 equivalents, preferably 1-30 equivalents, per 1 equivalent of compound (29), however, this number depends on the connection type and the used solvent and other reaction conditions.

The reaction can be carried out usually at a temperature of from 0°C to the boiling point of the solvent, preferably from 50°to 100°C.

The reaction time is from 0.5 hours to 0 hours, preferably 1-24 hours.

Used at this stage, the solvent includes, preferably, methanol, ethanol, isopropanol, dioxane, dimethoxyethane, ethylene glycol, and the like, and more preferred is isopropanol or dioxane.

Thus obtained compound (30) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, compound (30) can be used at a later stage without purification.

Stage 17

At this stage, carboxylic acid (30), obtained in stage 16, is introduced into reaction with the compound (2)to give compound (31). The reaction at this stage can be carried out in the same manner as in stage 1, 8, or the like, using leading to the formation of amide linkages reaction as described previously (Basic Principle and Experiments in Peptide Syntheses, Nobuo Izumiya, etc., Maruzen Co., Ltd., 1983; Comprehensive Organic Synthesis, 6, Pergamon Press, 1991), a corresponding method, or a combination of them and the standard methods.

The amount of compound (2), which should be used, and conditions, such as solvent for the reaction and the reaction temperature may be the same as in the case leading to the formation of amide linkages reaction in stage 1, 8, or similar treatment is om.

Thus obtained compound (31) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth.

The compound (I-7), i.e. the compounds of formula (I)according to the present invention, in which-X1-R1means-CH2-Cm-R1can be obtained in the following way (in this case, Cm means a divalent saturated hydrocarbon group with 2-5 carbon atoms, where one of the carbon atoms may be replaced by a nitrogen atom, an oxygen atom or a sulfur atom; R1has the same meanings as above).

(where the symbols have the same meanings as above)

Stage 18

At this stage, introducing a protective group for the carboxyl group of compound (32)to give compound (33).

The introduction of protective groups for carboxyl can be carried out, for example, in the same way as described in the case of stage 4, the previously described method (Protective Groups in Organic Synthesis, T.W. Green, 2-e edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard methods.

Thus obtained compound (33) can be isolated and purified in the usual way, for example by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (33) can be used at a later stage without purification.

Stage 19

At this stage, the compound (33), obtained in stage 1, is introduced into reaction with m-chloroperoxybenzoic acid (mCPBA)to give compound (34). The amount of mCPBA, which should be used at this stage, and conditions such as reaction temperature and the solvent for the reaction, can be the same as described in the case of stage 12. Thus obtained compound (34) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, compound (34) can be used at a later stage without purification.

Stage 20

At this stage, the compound (34)obtained in stage (19), is introduced into reaction with POCl3receiving connection (35).

The number of POCl3that should be used per 1 equivalent of compound (34) at this stage, and conditions such as reaction temperature and reaction time may be the same as described in the case of stage 13. Thus obtained compound (35) can be isolated and purified in the usual way, for example, potamanthidae, vacuum distillation, solvent extraction, the resultant deposition rates, crystallization, chromatography, and so forth. Alternatively, compound (35) can be used at a later stage without purification.

Stage 21

At this stage, from the compound (35)obtained in stage 20, remove the protective group for carboxyl, receiving a connection (36).

The removal of the protective group W in the case of a carboxyl group at this stage can be carried out in the same way as described in the case of stage 7, in accordance with the previously described method (Protective Groups in Organic Synthesis, T.W. Green, 2-e edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard ways. Thus obtained compound (36) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, compound (36) can be used at a later stage without purification.

Stage 22

At this stage, the compound (36)obtained in stage 21, is introduced into reaction with the compound (2)to give compound (37). The reaction at this stage can be carried out in the same way as described in the case of reactions leading to the formation of amide linkages, at stage 1, 8, or the like. The thus obtained Conn the imposition of (37) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth. Alternatively, the compound (37) can be used at a later stage without purification.

Stage 23

At this stage, the compound (37)obtained in stage 22, is introduced into reaction with the compound (14) in the presence of a base, receiving the connection (38). The reaction at this stage can be carried out in the same way as described in the case of stage 2. Thus obtained compound (38) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, the resultant deposition rates, crystallization, chromatography, and so forth. Alternatively, compound (38) can be used at a later stage without purification.

Stage 24

At this stage, the connection (38)obtained in stage (23), is introduced into reaction with NaBH4receiving connection (39). The reaction at this stage can be carried out as described previously (Comprehensive Organic Synthesis), a corresponding method, or a combination of them and the standard ways. The number of NaBH4that should be used is usually 0.2 to 30 equivalents, predpochtiteljno, 1-10 equivalents, per 1 equivalent of compound (38), however, it depends on the type of connection (38) and used Rast is orites and other reaction conditions.

The reaction can be carried out usually at a temperature of from -78°C to the boiling point of the solvent, preferably -10°C to 40°C.

The reaction time is usually 0.1 to 24 hours, preferably 0.2 to 5 hours.

With regard to use at this stage of the solvent, there can be used any type of solvent, if it has no adverse effect on the reaction, e.g., preferably methanol, ethanol, isopropanol, tetrahydrofuran, and the like, and more preferred is methanol or ethanol. Thus obtained compound (39) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, the resultant deposition rates, crystallization, chromatography, and so forth. Alternatively, compound (39) can be used at a later stage without purification.

Stage 25

At this stage, the compound (39)obtained in stage (24)is injected into the reaction of HSi(C2H5)3receiving the compound (I-7). Conducted at this stage of recovery can be carried out as described previously (J.O.C., 53, No. 22, 5301-5304 (1988)), a corresponding method, or a combination of them and the standard methods.

The number of HSi(C2H5)3that should be used is usually 0.5 to 10 equivalents, preferably 1-10 equivalents, per 1 equivalent of compound (39), however, it depends on the type of connection (39) and the used solvent and other reaction conditions.

The reaction can be carried out usually within 0.2 to 30 hours, preferably 0.5 to 10 hours.

The reaction temperature is from -10°C to the boiling point of the solvent, preferably from 0°C to the boiling point of the solvent.

With regard to use at this stage of the solvent, there can be used any type of solvent, if it has no adverse effect on the reaction, for example, including, preferably, triperoxonane acid. Thus obtained compound (I-7) can be isolated and purified in the usual way, for example, by concentration, vacuum distillation, solvent extraction, crystallization, resultant deposition rates, chromatography, and so forth.

At this stage, when R2or R3means lower CNS group, the hydrogen atom of the alkyl part of alkoxygroup may be substituted by a hydroxyl group or amino group, and in this case, if necessary, introducing or removing protective for hydroxyl group or aminosidine group can be carried out by any means described in the case of stages 1-25.

Introduction or removal of the protective group can be carried is tvline previously described method (Protective Groups in Organic Synthesis) the corresponding method, or a combination of them and the standard methods.

In addition, when the cycle A, R1or the cycle contains one or more substituents, it may be possible to conduct the reaction at each stage by the introduction or removal of the protective group or groups, in accordance with the necessity, in the case of each Deputy.

The reaction for the introduction or removal of the protective group can be carried out as described previously (Protective Groups in Organic Synthesis, T.W. Green, 2-e edition, John Wiley and Sons, 1991), a corresponding method, or a combination of them and the standard methods.

Derivatives of pyridine-2-carboxamide, obtained according to the invention, are sometimes in the form of pharmaceutically acceptable salts, which can be obtained in a standard way using the compounds of formulas (I-1), (I-2), (I-3), (I-4), (I-5), (I-6) and (I-7)related to compounds of formula (I) according to the present invention.

In particular, when the compounds of formulas (I-1), (I-2), (I-3), (I-4), (I-5), (I-6) and (I-7) contain a basic group or a group derived from amino or peredelnoj group, in the molecule, by treatment with acid, they can be converted into the corresponding pharmaceutically acceptable salt.

Additive salts of the acids include, for example, salts halogenation acids, such as hydrochloride, hydroptere, hydrobromide and hydroid is d; inorganic salts such as nitrate, perchlorate, sulfate, phosphate and carbonate; lower alkyl sulphonates, such as methanesulfonate, triftorbyenzola and econsultant; arylsulfonate, such as bansilalpet and p-toluensulfonate; organic acid salts such as fumarate, succinate, citrate, tartrate, oxalate and maleate; and additive salts of amino acids such as glutamate and aspartate. When the compounds according to the present invention contain an acidic group or an acidic group in its substituents, for example, carboxyl group, by treatment with base, they can be converted into the corresponding pharmaceutically acceptable salt. Additive salts of the bases include, for example, alkali metal salts such as sodium salt and potassium salt; salts of alkaline earth metals such as calcium salts or magnesium salts; and salts of organic bases, such as ammonium salt, guanidine, triethylamine and dicyclohexylamine. In addition, the compounds according to the present invention can be optionally form of hydrate or solvate of the free compounds or salts.

The compounds of formula (I) can be used to produce medicines for the prevention or preventive or therapeutic treatment in case of diabetes mellitus type 2, or disease or status is I, associated with him, by combining the compounds of formula (I) with the media.

Prophylactic or therapeutic dose of a compound of formula (I)can, of course, vary depending on the nature treatable condition, select a specific connection and the way of its introduction.

It can also vary in accordance with age, weight and response of the individual patient. Usually, the daily dose ranges from about 0.001 mg to about 100 mg per kg of body weight, preferably, from about 0.01 mg to about 50 mg / kg and, more preferably, from about 0.1 mg to 10 mg per kg, in single or divided doses. In some cases, it may be necessary to use dosages outside these limits.

An example of a suitable oral dose is a dose from about 0.01 mg to approximately 2.0 g, administered orally in the form of a single or divided doses, two to four times per day. Preferably, the dose ranges from about 1.0 mg to about 200 mg per day, administered once or twice per day. More preferably, the dose is about 10-100 mg, administered once daily.

When carry out intravenous or oral administration, the typical dose ranges from about 0.001 mg to about 100 mg (preferably from 0.01 mg to about 10 mg) of the compounds of formula (I) n the kg of body weight per day, and, more preferably, from about 0.1 mg to about 10 mg of the compounds of formula (I) per kg of body weight per day.

As indicated above, the pharmaceutical composition includes the compound of formula (I) and a pharmaceutically acceptable carrier. The term "composition" refers to a product comprising the active ingredient and the inert ingredient (active and inert ingredients), pharmaceutically acceptable excipients that make up the carrier, as well as the product that is obtained, directly or indirectly, as a result of combining, kompleksoobrazovanija or aggregation of any two or more ingredients, or as a result of dissociation of one or more of the ingredients, or from other types of reactions or interactions between the ingredients.

Preferably, the composition includes a compound of formula (I) in an amount that is effective to treat, prevent or delay the appearance of diabetes type 2 in combination with a pharmaceutically acceptable carrier.

Can be used any suitable route of administration for providing a mammal, especially human, an effective dose of a compound according to the present invention. Can be used, for example, oral, rectal, local, intravenous, ocular, pulmonary, nasal route of administration, and the like. Examples of Lekarstvo the x forms include tablets, tablets, dispersions, suspensions, solutions, capsules, creams, ointments, aerosols, and the like, preferably oral tablets.

When receiving oral input compositions may be used any of the usual pharmaceutical media, such as, for example, water, glycols, oils, alcohols, flavoring, preservatives, dyes and the like in the case of oral injected fluids, which can serve as suspensions, elixirs and solutions; or carriers may include starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, dezintegriruetsja agents, and the like; oral introduce solids can include powders, capsules and tablets, preferably oral input of hard drugs.

Because of the ease of their administration tablets and capsules represent the most preferred single oral dosage form. If desired, the tablets can be provided with a coating by standard aqueous or non-aqueous methods of application.

In addition to the common dosage forms listed above, the compounds of formula (I) can also be entered by using the means for controlled release and/or delivery of drugs, such as described in U.S. patent 3845770, 3916899, 356809, 3598123, 3630200 and 4008719.

The pharmaceutical compositions according to the present invention suitable for oral administration may be, for example, in the form of capsules, starch wafers or tablets, each of which contains a defined amount of the active ingredient, as a powder or granules, or suspensions in an aqueous liquid, non-aqueous liquid, emulsion, oil-in-water or liquid emulsion, water-in-oil". Such compositions can be obtained by any method known in pharmacy, but all methods include the stage of mixing the active ingredient with a carrier that includes one or more necessary ingredients.

The compositions are generally obtained through homogeneous and thoroughly mixing the active ingredient with liquid carriers or finely ground solid carriers or both types of media and then, if necessary, provide the product with the appropriate form. For example, a tablet may be obtained by extrusion or molding, optionally, together with one or more auxiliary ingredients. Molded tablets may be made by molding in a suitable machine the active ingredient in free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active substance or dispersal the rum.

Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. Preferably, each tablet contains from about 1 mg to about 1 g of the active ingredient and each wafer or capsule contains from about 1 mg to 500 mg of active ingredient.

Below are examples of dosage forms for the compounds of formula (I):

Table 1

Suspension for injection (intramuscularly)
mg/ml
The compound of formula (I)10
The methylcellulose5,0
Tween 800,5
Benzyl alcohol : 9,0
Benzylaniline1,0
Water for injection add up to the total number of 1.0 ml

Table 2

Tablet
mg tablet
The compound of formula (I)25
The methylcellulose415
Tween 8014,0
Benzyl alcohol : 43,5
Magnesium stearate2,5
Total: 500 mg

Table 3

Capsule
mg/capsule
The compound of formula (I)25
The lactose powder573,5
Magnesium stearate2,5
Total: 600 mg

Table 4

Aerosol
On the 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 used in the treatment/prevention/slowing the appearance of diabetes type 2, and also at diseases and conditions associated with diabetes mellitus type 2. Other drugs may be administered by and in the quantity that is usually used for them, simultaneously or sequentially with the unity of formula (I).

When the compound of formula (I) is used simultaneously with one or more other drugs, a preferred composition containing other drugs in addition to the compound of formula (I). Thus, pharmaceutical compositions according to the present invention include compositions that also contain one or more other active ingredients in addition to the compound of formula (I). Examples of other active ingredients that may be combined with the compound of the formula (I), administered either separately or in the same pharmaceutical compositions, include, but are not exhaustive follows:

(a) biguanide (such as buformin, Metformin, phenformin);

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

(C) insulin;

(d) somatostatin;

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

(f) stimulants of insulin secretion (for example, acetohexamide, carbutamide, hlorpropamid, glibornuride, gliclazide, glimepiride, glipizide, gliquidone, glisoxepide, gliburid, glyhexamide, pipename, fenbutatin, tolazamide, tolbutamide, tolciclate, nateglinide, Repaglinide).

The mass ratio of the compounds of formula (I) to the second active ingredient may vary within wide limits and depends on the effective dose of each ingredient So that for example, when the compound of formula (I) combine with a PPAR agonist, a mass ratio of the compounds of formula (I) PPAR agonist typically ranges from about 1000:1 to about 1:1000, preferably, from about 200:1 to about 1:200. Combinations of the compounds of formula (I) with other active ingredients usually are in the above ranges, however, in each case must be used effective dose of each active ingredient.

Below demonstrates ability to activate glucokinase compounds of formula (I) according to the present invention and the method of its determination.

Excellent in relation to the activation of glucokinase ability of the compounds of formula (I) can be determined as described previously (Diabetes, 45, 1671-1677 (1996)) or the corresponding method.

Glucokinase activity can be installed without the direct determination of glucose-6-phosphate by measuring the amount of thionicotinamide-adenine-dinucleotide (thio-NADH)generated at the time of receipt of phosphogluconolactonase of glucose-6-phosphate with the help of reporter enzyme glucose-6-phosphate dehydrogenase (G6PDH). Therefore, it may be determined by the degree glucokinase activity.

Used in the analysis of recombinant GK (glucokinase) human liver, expressed in the form of a slit crack is on the FLAG in E. coli was purified on ANTIFLAG M2 AFFINITY GEL (Sigma).

The analysis was carried out at a temperature of 30°96-hole tablet. On the tablet were distributed 69 μl of each buffer for analysis (25 mm HEPES-buffer: pH 7.2; 2 mm MgCl2, 1 mm ATP, 0.5 mm TNAD, 1 mm dithiothreitol), to which was added 1 μl of a solution of the compound in dimethyl sulfoxide or dimethyl sulfoxide as a control. Then there was distributing 20 ál of pre-chilled ice mixture of enzymes (FLAG-GK, 20 Ed./ml G6PDH), to which was added 10 μl of 25 mm glucose as substrate to initiate the reaction (final glucose concentration=2.5 mm).

After start of the reaction every 30 seconds for 10 minutes was determined by absorption at 405 nm for the evaluation of compounds based on the initial increase within 5 minutes. FLAG-GK was added to increase absorption after 5 minutes was reduced to a value of from 0.05 to 0.1 in the presence of 1% DMSO.

Estimated value of the optical density (OD) of the respective compounds were determined at the respective concentrations, and the magnitude of the OD of dimethyl sulfoxide used as a control was taken as 100%. From the OD values at corresponding concentrations expected Emax (%) and ES (µmol) and used as indicators of the ability of compounds in relation to the activation of glucokinase. According to the above analysis of the definition is whether the ability of the compounds according to the present invention to activate glucokinase. The results are presented in table 5.

Table 5
Connection # Emax (%)EC50 (µm)
Example obtain 19970,05
Example of getting 710670,06
Example 308180,12

As can be seen from table 5, the compounds according to the present invention have sufficient to activate glucokinase ability, when Emax and IS used as indicators.

Below the present invention is illustrated more specifically by using preparative examples and examples of the preparation, and the present invention is in no way limited in the scope of its protection.

Example compositions 1

The connection according to the example of obtaining 1 (10 parts), 15 parts of pure magnesium oxide and 75 parts of lactose is homogeneous mixed to obtain a powder diluted composition in the form of powder or fine powder with a particle size of not larger than 350 μm. The diluted powder composition is administered in capsule container for receiving the encapsulated drugs.

Example composition 2

The connection according to the example of obtaining 1 (45 parts), 15 frequent the th starch, 16 parts of lactose, 21 parts of crystalline cellulose, 3 parts of polyvinyl alcohol and 30 parts of distilled water is homogeneous mix, disintegrate, granularit, dried and sieved to obtain a granulated product with a diameter of granules from 1410 to 177 μm.

An example of the composition 3

After obtaining a granulated preparation method described in example getting 2 to 96 parts of granulirovannogo drug add 3 parts of calcium stearate, and then subjected to direct pressing, obtaining tablets with a diameter of 10 mm

An example of the composition 4

To 90 parts of a granular preparation obtained by the method described in example getting 2 add 10 parts of crystalline cellulose and 3 parts of calcium stearate, and then subjected to direct pressing with obtaining tablets with a diameter of 8 mm To add a mixed suspension of gelatin syrup and precipitated calcium carbonate, getting a tablet with a coating of sugar.

In the case of thin-layer chromatography according to the examples, using silica gel 60F245(Merck) plates and in the case of a detection method using a UV detector. As silica gel for column using WakogelTMC-300 (Wako Pure Chemical), whereas as silica gel for the column with reversed phase using LC-SorbTMSP-B-ODS (Chemco) or YMC-GelTMODS-AQ 120-S50 (Yamamura Depending Kenyusho).

Listed below are the values of the abbreviations in the following examples:

i-Bu: isobutylene group

n-Bu: n-bucilina group

t-Bu: tert-bucilina group

Me: methyl group

Et: ethyl group

Ph: phenyl group

i-Pr: isopropyl group

n-Pr: n-sawn group

CDCl3fully deuterated chloroform

CD3OD: fully deuterated methanol

DMSO-d6fully deuterated dimethylsulfoxide

Listed below are the values of the abbreviations for the spectrum of nuclear magnetic resonance:

s: singlet;

d: doublet;

dd: doublet of doublets;

t: triplet;

m: multiplet;

br: extended;

q: Quartet;

J: the interaction constant;

Hz: Hertz.

Example obtain 1

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-yl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

To a solution (400 ml) 14.1 g (73,0 mmol) 3,b-dichloro-2-pyridineboronic acid in chloroform successively added 9.00 g (89,9 mmol) aminothiazole, 12,1 g (of 89.7 mmol) of N-hydroxybenzotriazole and 19.0 g (99,2 mmol) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, followed by stirring at room temperature for 24 hours. Then the reaction solution is concentrated and to the residue is added ethyl acetate, then washed with 0,2n. aqueous solution horologer is Yes, water and aqueous saturated sodium hydrogen carbonate solution. After drying and concentrating, the resulting residue is crystallized from a mixed solvent consisting of hexane and ethyl acetate (5:1)to give 12.8 g (yield: 64%) of 3,6-dichloro-N-(thiazol-2-yl)-2-pyridinecarboxamide in a solid white color.

To a solution (10 ml) 1.27 g (with 4.64 mmol) obtained dichloroethylene in N,N-dimethylformamide added to 1.25 g (9,04 mmol) of potassium carbonate and 605 μl (4,87 mmol) of 4-methoxythiophene, then stirred at room temperature for 24 hours. To the reaction solution was added water, and then extracted with ethyl acetate and washed with aqueous saturated solution of sodium chloride. After drying and concentrating, the resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=4:1 to 1:1)to give 1.70 g (yield: 97%) of 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide in a solid white color.

To a solution (10 ml) 705 mg (of 1.87 mmol) obtained 6-chlorinated in N,N-dimethylformamide added 350 mg (2,53 mmol) of potassium carbonate and 285 mg (2.82 mmol) of 3-mercapto-1,2,4-triazole, and then refluxed for 35 hours. To the reaction solution, water is added and after extraction three times with chloroform, the organic layer is dried and concentrated in vacuo. the received residue purified column chromatography on silica gel (chloroform:methanol=100:1) and crystallization from a mixed solvent, consisting of hexane and ethyl acetate (1:1)to give 410 mg (yield: 50%) specified in the connection header in the form of a solid white color.

1H-NMR (CDCl3) δ: a 3.87 (3H, s), 6,07-7,07 (4H, m), 7,22 (1H, d, J=8.7 Hz), was 7.45 (1H, d, J=3.6 Hz), 7,49 (2H, d, J=9.0 Hz), 8,35 (1H, s).

MS (ESI) mass spectrometry with ionization electron spray) m/e: 443 [M+H]+.

Compounds according to examples of the preparation 2-51 get in the way described in the above example, obtaining 1. Analytical data for these compounds are presented below.

Example of getting 2

Obtaining 3-(4-perpenicular)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The compound according to example getting 2 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, the application of the General method with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 4-portifino and 3-mercapto-4-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.42 (3H, s), 3,74 (3H, s), 6,62 (1H, s), 7,00 (1H, d, J=9.0 Hz), 7,10 (1H, d, J=9.0 Hz), 7,17 (2H, m), 7,53 (2H, m), 8,40 (1H, s)

MS (ESI) m/e: 459 [M+H]+.

Example for the preparation of 3

Obtaining 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-yl)-2-pyridinecarboxamide

The connection according to the example of getting 3 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 4-portifino and 3-mercapto-1,2,4-triazole.

1N-NMR (CDCl3) δ: is 2.40 (3H, s), is 6.61 (1H, s), 7,01 (1H, d, J=9.3 Hz), 7,17-of 7.25 (3H, m), 7,58 (2H, m), 8,35 (1H, s)

MS (ESI) m/e: 445 [M+H]+.

Example 4

Obtaining 3-(4-perpenicular)-6-(1-Mei-2-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The compound according to example 4 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 4-portifino and 3-mercapto-4-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.41 (3H, s), of 3.73 (3H, s), 6,60 (1H, s), 6,77 (1H, d, J=8.7 Hz), 6,92 (1H, d, J=8.7 Hz), 7,10-7,22 (4H, m), 7,52 (2H, m)

MS (ESI) m/e: 458 [M+H]+.

Example of getting 5

Obtaining 3-(4-perpenicular)-6-(1-methyl-1H-tetrazol-5-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 5 can be obtained by the method described in example floor is placed 1, the corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 4-portifino and 5-mercapto-1-methylthiazole.

1H-NMR (CDCl3) δ: 2,43 (3H, s), of 4.12 (3H, s), of 6.65 (1H, s), 7,12 (1H, d, J=9.0 Hz), 7,21 (2H, m), 7,45 (1H, d, J=9.0 Hz), 7,58 (2H, m)

MS (ESI) m/e: 460 [M+H]+.

An example of obtaining 6

Obtaining 3-(cyclohexylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 6 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, cyclohexanol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 1,20-1,75 (6N, m)of 1.84 (2H, m)to 2.06 (2H, m), a 2.36 (3H, s)of 3.25 (1H, m), 6,56 (1H, s), the 7.43 (1H, d, J=8.7 Hz), to 7.64 (1H, d, J=8.7 Hz), with 8.33 (1H, s)

MS (ESI) m/e: 433 [M+H]+.

Example of getting 7

Obtaining 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 7 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of what Finance 3, 6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,01 (1H, d, J=8.7 Hz), to 7.09 (1H, d, J=3.6 Hz), 7,19 (2H, m), 7,25 (1H, d, J=8.7 Hz), to 7.50 (1H, d, J=3.6 Hz), to 7.50 (2H, m), 8,35 (1H, s)

MS (ESI) m/e: 431 [M+H]+.

Example obtain 8

Obtaining 3-(thiazol-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-yl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 8 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 2-mercaptothiazole and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) 5: 2,40 (3H, s), 6,60 (1H, m), 7,30 and 7.36 (2H, m), to 7.59 (1H, d, J=3.6 Hz), 8,02 (1H, d, J=3.6 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 434 [M+H]+.

Example of getting 9

Obtaining 3-(2-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 9 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 2-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3 ) δ: 7,01? 7.04 baby mortality (2H, m), 7,2-7,28 (3H, m), 7,46 (1H, d, J=3.6 Hz), 7,51-to 7.64 (2H, m), at 8.36 (1H, s)

MS (ESI) m/e: 431 [M+H]+.

Example 10

Obtaining 3-phenylsulfonyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example 10 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,02-to 7.09 (2H, m), 7,24 (1H, d, J=8.7 Hz), 7,47-7,53 (4H, m), EUR 7.57-7,63 (2H, m), scored 8.38 (1H, s)

MS (ESI) m/e: 413 [M+H]+.

Example of getting 11

Obtaining 3-(4-torpedolike)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 11 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-terfenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ:? 7.04 baby mortality (1H, d, J=3.6 Hz), 7,05-7,13 (4H, m), 7,24 (1H, d, J=8.7 Hz), 7,46-7,51 (2H, m), 8,32 (1H, s)

MS (ESI) m/e: 415 [M+H]+.

Example 12

Obtaining 3-(4-methoxyphenyl tilsley)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example 12 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-methoxybenzylamine and 3-mercapto-4-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,76 (3H, s), with 3.79 (3H, s), 4,11 (2H, s), at 6.84 (2H, d, J=8,8 Hz), 7,01 (1H, d, J=3.2 Hz), 7,30 (1H, d, J=8,8 Hz), 7,32 (2H, d, J=8,8 Hz), 7, 51 (1H, d, J=3.2 Hz), the 7.65 (1H, d, J=8,8 Hz), 8,44 (1H, s)

MS (ESI) m/e: 471 [M+H]+.

Example of getting 13

Obtaining 3-(3-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 13 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 3-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,02 (1H, d, J=3.6 Hz), 7,05 (1H, d, J=8,4 Hz), 7,18 (1H, TD, J=8,4 Hz, 3.2 Hz), 7,24 (1H, d, J=8,4 Hz), 7,29 (1H, DDD, J=8,4 Hz, 2.8 Hz, 2.8 Hz), was 7.36 (1H, d, J=7,6 Hz), 7,42-of 7.48 (2H, m), 8,35 (1H, C)

MC (ESI) m/e: 431 [M+H]+.

Example of getting 14

Obtaining 3-(2,4-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide the

The connection according to the example of getting 14 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 2,4-Divertimento and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 6,98-7,05 (4H, m), 7,28 (1H, d, J=8,8 Hz), 7,46 (1H, d, J=3.6 Hz), 7,58-to 7.64 (1H, m), at 8.36 (1H, s)

MC (ESI) m/e: 449 [M+H]+.

Example get 15

Obtaining 3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 15 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, using 3, 6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-portifino and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.58 (3H, s), 6,97 (1H, d, J=8,4 Hz),? 7.04 baby mortality (1H, d, J=3.6 Hz), 7,15-of 7.23 (3H, m), of 7.48 (1H, d, J=3.6 Hz), 7,54-7,58 (2H, m)

MS (ESI) m/e: 445 [M+H]+.

Example 16

Obtaining 3-(4-cyanobenzylidene)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example 16 can be obtained by the method described in example obtaining 1 that is relevant to the existing method, or a combination of them and the standard ways, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-cyanothiophene and 3-mercapto-1, 2, 4-triazole.

1H-NMR (CDCl3) δ: 7,06 (1H, d, J=3.6 Hz), 7,11 (1H, d, J=8,8 Hz), 7,30 (1H, d, J=8,8 Hz), 7,49 (1H, d, J=3.6 Hz), the 7.65 (2H, d, J=8,8 Hz), 7,73 (2H, d, J=8,8 Hz), 8,40 (1H, s)

MC (ESI) m/e 438 [M+H]+.

Example of getting 17

Obtaining 3-(pyridine-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 17 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 7.09 (1H, d, J=3.6 Hz), 7,28-to 7.35 (2H, m), the 7.43 (2H, d, J=6.0 Hz), 7,51 (1H, d, J=3.6 Hz), 8,39 (1H, s), to 8.62 (2H, d, J=6, 0 Hz)

MC (ESI) m/e: 414 [M+H]+.

Example of getting 18

Obtaining 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 18 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazolo[5,4-b]Piri is in, 4-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,00 (1H, d, J=8,8 Hz), 7,16-7,20 (2H, m), 7,25 (1H, d, J=8,8 Hz), 7,37-7,41 (1H, m), 7,55-7,58 (2H, m), 8,02 (1H, d, J=8,4 Hz), 8,42 (1H, s), 8,51 (1H, d, J=4.4 Hz)

MS (ESI) m/e: 482 [M+H]+.

Example of getting 19

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 19 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methoxymethanol, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.43 (3H, s), 3,86 (3H, s), 4,51 (2H, s), 6,92 (1H, s), 6, 96-7,02 (3H, m), 7,22 (1H, d, J=8.7 Hz), 7,49 (2H, d, J=8.7 Hz), 8,35 (1H, s)

MC (ESI) m/e: 487 [M+H]+.

Example of getting 20

Obtaining 3-(4-acetylphenylalanine)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 20 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-acetylthiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.65 (3H, s), 7,05 (1H, d, J=3.6 Hz), 7,10 (1H, d, J=8,4 Hz), 7,25 (1H, d, J=8,4 Hz), 7,47 (1H, d, J=3.6 Hz), the 7.65 (2H, d, J=8.6 Hz), 8,01 (2H, d, J=8.6 Hz), at 8.36 (1H, s)

MC (ESI) m/e: 455 [M+H]+.

Example of getting 21

Obtaining 3-(thiophene-2-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 21 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 2-mercaptothiazoline and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,01 (1H, d, J=3.2 Hz), 7,06 (1H, d, J=8,8 Hz), 7,16 (1H, DD, J=3,6, 5,2 Hz), 7,26 (1H, d, J=8,8 Hz), 7,35 (1H, DD, J=1,2, 3,6 Hz), the 7.43 (1H, d, J=3.2 Hz), 7,60 (1H, DD, J=1,2, 5,2 Hz), 8,35 (1H, C)

MS (ESI) m/e: 419 [M+H]+.

Example of getting 22

Obtaining 3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 22 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-methoxybutyrophenone and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) #x003B4; : of 3.46 (3H, s), 4,50 (2H, s), 7,00 (1H, d, J=3.2 Hz), 7,02 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=8,8 Hz), 7,42 (1H, d, J=3.2 Hz), the 7.43 (2H, d, J=8.0 Hz), 7,54 (2H, d, J=8.0 Hz), with 8.33 (1H, s)

MC (ESI) m/e: 457 [M+H]+.

An example of retrieving 23

Obtaining 3-(4-perpenicular)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 23 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazolo[5,4-b]pyridine, 4-portifino and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.54 (3H, s), of 6.96 (1H, d, J=8,8 Hz), 7,11-7,16 (2H, m), 7,17 (1H, d, J=8,8 Hz), 7,37 (1H, DD, J=4,8, 8.0 Hz), 7,50-rate of 7.54 (2H, m), of 8.00 (1H, d, J=8.0 Hz), to 8.45 (1H, d, J=4,8 Hz)

MC (ESI) m/e: 496 [M+H]+.

Example of getting 24

Obtaining 3-(4-methylphenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 24 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methoxymethanol, 4-methylthiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl 3) δ: to 2.42 (3H, s), 3.43 points (3H, s), 4,51 (2H, s)6,91 (1H, s), 7,00 (1H, d, J=8,8 Hz), 7,19 (1H, d, J=8,8 Hz), 7,26 (2H, d, J=8,4 Hz), 7,44 (2H, d, J=8,4 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 471 [M+H]+.

Example get 25

Obtaining 3-(4-chlorophenylsulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 25 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methoxymethanol, 4-chlorothiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.43 (3H, s), 4,50 (2H, s)6,91 (1H, s), 6,97 (1H, d, J=8,8 Hz), 7,20 (1H, d, J=8,8 Hz), 7,42 (2H, d, J=8,4 Hz), 7,49 (2H, D, J=8,4 Hz), with 8.33 (1H, s)

MC (ESI) m/e: 491 [M+H]+.

Example of getting 26

Obtaining 3-(4-perpenicular)-6-(3H-[1,2,4]triazole-4-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 26 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methoxymethanol, 4-portifino and 4-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 6.66 (1H, d, J=8,8 Hz), 6,72 (1H,d, J=8,8 Hz)6,86 (1H, d, J=4.0 Hz), 6.89 in-6,94 (2H, m), 7,25 (1H, d, J=4.0 Hz), 7,27-7,30 (2H, m), 7,72 (1H, s)

MC (ESI) m/e: 431 [M+H]+.

Example of getting 27

Obtaining 3-(4-methylsulfonylbenzoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 27 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-methylsulfonylmethane and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.12 (3H, s), 7,05 (1H, d, J=3, 6 Hz), 7,11 (1H, d, J=8,8 Hz), 7,28 (1H, d, J=8,8 Hz), of 7.48 (1H, d, J=3.6 Hz), 7,74 (2H, d, J=8.0 Hz), 8,00 (2H, d, J=8.0 Hz) 8,39 (1H, s)

MS (ESI) m/e: 491 [M+H]+.

Example of getting 28

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-hydroxymethylimidazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 28 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-hydroxymethylimidazole, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,86 (3H, s), 4,78 (2H, s), of 6.99 (2H, d, J=8,8 Hz), 7,02 (1H, is, J=8,8 Hz), 7,18 (1H, d, J=8,8 Hz), 7,35 (1H, s), 7,46 (2H, d, J=8,8 Hz), 8,39 (1H, s)

MC (ESI) m/e: 473 [M+H]+.

An example of obtaining 29

Obtaining 3-(4-perpenicular)-6-(5-methoxymethyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 29 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-portifino and 3-mercapto-5-methoxymethyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,50 (3H, s), was 4.76 (2H, s), 6,98 (1H, d, J=8,8 Hz), 7,03 (1H, d, J=3.2 Hz), 7,14-7,22 (3H, m), of 7.48 (1H, d, J=3.2 Hz), 7,54-EUR 7.57 (2H, m)

MS (ESI) m/e): 475 [M+H]+.

Example 30

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example 30 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (DMSO-d6) δ: of 2.51 (3H, s), 7,17 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=8,8 Hz), 7,35 (1H, d, J=3.6 Hz), was 7.36 (1H, d, J=8,8 Hz), EUR 7.57 (1H, d, J=3.6 Hz) 7,83 (1H, DD, J=2,4, 8,8 Hz), 8,53 (1H, d, J=2.4 Hz), 8,72 (1H, s)

MS (ESI) m/e): 428 [M+H]+.

An example of retrieving 31

Obtaining 3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 31 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-dimethylcarbamodithioato and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 3.02 (3H, s) a 3.15 (3H, s),? 7.04 baby mortality (1H, d, J=3.6 Hz), 7,06 (1H, d, J=8,8 Hz), 7.23 percent (1H, d, J=8,8 Hz), 7,49 (1H, d, J=3.6 Hz), to 7.50 (2H, d, J=8,4 Hz), to 7.61 (2H, d, J=8,4 Hz), 8,39 (1H, s)

MC (ESI) m/e: 484 [M+H]+.

Example of getting 32

Obtaining 3-(4-triftormetilfullerenov)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 32 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, using 3, 6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-triptoreline and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ:? 7.04 baby mortality (1H, d, J=3.6 Hz), 7,06 (1H, d, J=8,8 Hz), 7,26 (1H, d, J=8,8 Hz), 7,47 (1H, d, J=3.6 Hz), 7,66-7,74 (4H, m), scored 8.38 (1H s)

MS (ESI) m/e: 481 [M+H]+.

An example of obtaining 33

Obtaining 3-(4-methylcarbamoylmethyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 33 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-methylcarbamoylmethyl and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,00 (3H, d, J=4,8 Hz), 7,02 (1H, d, J=8,8 Hz), 7,05 (1H, d, J=3.6 Hz), 7,20 (1H, d, J=8,8 Hz), 7,47 (1H, d, J=3.6 Hz), to 7.59 (2H, d, J=8,4 Hz), 7,81 (2H, d, J=8,4 Hz), 8,32 (1H, s)

MC (ESI) m/e: 470 [M+H]+.

An example of retrieving 34

Obtaining 3-(hydroxyethylaminomethyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 34 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-hydroxyethylaminophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.97 (2H, m), 4,13 (2H, m), 7,00-7,11 (4H, m), 7.23 percent (1H, d, J=9.0 Hz), 7, 46-7, 54 (3H, m), at 8.36 (1H, s)

MC (ESI) m/e: 473 [M+H]+.

Example polucheniya

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-dimethylaminomethylene-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 35 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-5-dimethylaminomethylphenol, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,32 (6N, (C), 3,70 (2H, s), 3,85 (3H, s), 6,97 (2H, d, J=8,8 Hz), 7,00 (1H, d, J=8.5 Hz), 7,19 (1H, d, J=8.5 Hz), 7,26 (1H, s), 7,46 (2H, d, J=8,8 Hz), 8,31 (1H, s)

MS (ESI) m/e: 500 [M+H]+.

Example of getting 36

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 36 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-dimethylaminomethylphenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,40 (6N, C)2,82 (2H, t, J=5.6 Hz), of 4.13 (2H, t, J=5.6 Hz), 6, 95-7,05 (4H, m), 7,21 (1H, d, J=8.7 Hz), 7,42-7,50 (MN, m), at 8.36 (1H, s), MC (ESI) m/e: 500 [M+H]+.

An example of retrieving 37

Obtaining 3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 37 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-hydroxyethylidene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.93 (2H, m), 3,90 (2H, m),? 7.04 baby mortality-7,10 (2H, m), 7.23 percent (1H, d, J=9.0 Hz), was 7.36 (2H, d, J=7, 8 Hz), of 7.48-7,56(3H, m), a 8.34 (1H, s)

MS (ESI) m/e: 457 [M+H]+.

An example of retrieving 38

Obtaining 3-(4-methylsulfinylphenyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 38 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-methylsulfonylmethane and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.97 (3H, s), 6,98 (1H, d, J=3.6 Hz), 7,21-of 7.25 (3H, m), 7,30 is 7.50 (4H, m), of 8.28 (1H, s)

MS (ESI) m/e: 505 [M+H]+.

An example of retrieving 39

Obtaining 3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(isoxazol the-3-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 39 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-aminoanisole, 4-dimethylcarbamodithioato and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: a 3.01 (3H, s)and 3.15 (3H, s), of 6.99 (1H, d, J=8,8 Hz), 7,19 (1H, d, J=8,8 Hz), 7,25 (1H, d, J=l,6 Hz), of 7.48 (2H, d, J=8.1 Hz), 7,56 (2H, d, J=8.1 Hz), 8,31 (1H, d, J=1.6 Hz), to 8.41 (1H, s)

MC (ESI) m/e: 468 [M+H]+.

Example of getting 40

Obtaining 3-(4-hydroxycyclohexyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example getting 40 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-mercaptoethanol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 1,30-1,60 (4H, m), 1,90-of 2.15 (4H, m), 3,10-up 3.22 (1H, m), 3,60-3,70 (1H, m), of 6.99 (1H, d, J=3, 6 Hz), 7,40 (1H, d, J=8,8 Hz), the 7.43 (1H, d, J=3.6 Hz), to 7.61 (1H, d, J=8,8 Hz), 8,32 (1H, s)

MS (ESI) m/e 435 [M+H]+.

An example of retrieving 41

Obtaining 3-(4-perpenicular)-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridazin-3-yl)-2-pyridinecarboxamide

Connect the tion according to the example of obtaining 41 can be obtained by way described in the example of a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-aminopyridine, 4-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 6.96 (1H, d, J=9,2 Hz), 7,12-7,16 (2H, m), 7,19 (1H, d, J=9,2 Hz), 7,50-of 7.55 (3H, m), to 8.41 (1H, s), 8,65 (1H, d, J=9,2 Hz), cent to 8.85 (1H, d, J=4,8 Hz)

MS (ESI) m/e): 426 [M+H]+.

An example of retrieving 42

Obtaining 3-(pyridine-2-intenlational)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 42 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 2-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,02 (1H, d, J=3.6 Hz), 7,39 (1H, d, J=8,8 Hz), was 7.45 (1H, d, J=3.6 Hz), to 7.68 (1H, d, J=8,8 Hz), scored 8.38 (1H, s), 8,44-8,46 (2H, m), to 8.70 (1H, d, J=1,6 Hz)

MC (ESI) m/e: 415 [M+H]+.

An example of retrieving 43

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 43 can be obtained by the method described in example a 1, a corresponding method, or what ombinarea and their standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminopyrazine, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.64 (3H, s), of 6.96 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=8,8 Hz), 7,28 (1H, d, J=8,l Hz), to 7.77 (1H, DD, J=8,1, 2.2 Hz), 8,29 (1H, DD, J=2,6, 1.5 Hz), 8,35 (1H, d, J=2.6 Hz), to 8.41 (1H, s), 8,61 (1H, d, J=2.2 Hz), 9,68 (1H, d, J=1.5 Hz)

MS (ESI) m/e): 423 [M+H]+.

An example of retrieving 44

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 44 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,39 (3H, s), 2.63 in (3H, s), to 6.58 (1H, s), of 6.99 (1H, d, J=8,8 Hz), 7,20-7,30 (2H, m), 7,74 (1H, d, J=8.0 Hz), 8,32 (1H, s), to 8.62 (1H, s)

MS (ESI) m/e): 442 [M+H]+.

An example of retrieving 45

Obtain 3-[4-(1-hydroxyethylaminomethyl)]-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 45 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard is x ways, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-(1-hydroxyethyl)-thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 1.52 (3H, d, J=6.4 Hz), equal to 4.97 (1H, q, J=6.4 Hz), 7,03 (1H, d, J=8,4 Hz), 7,06 (1H, d, J=3.6 Hz), 7,18 (1H, d, J=8,4 Hz), 7,47 (2H, d, J=8.0 Hz), of 7.48 (1H, d, J=3.6 Hz), 7,52 (2H, d, J=8.0 Hz,), a 8.34 (1H, s)

MC (ESI) m/e: 457 [M+H]+.

An example of retrieving 46

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(2-methylthiazole-4-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 46 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,63 (3H, s), of 2.72 (3H, s), of 6.96 (1H, d, J=8,4 Hz), 7,19 (1H, d, J=8.1 Hz), 7,27 (1H, d, J=8,4 Hz), 7,68 (1H, s), 7,76 (1H, DD, J=a 8.4 and 2.2 Hz), compared to 8.26 (1H, s), 8,59 (1H, d, J=2.2 Hz)

MS (ESI) m/e): 442 [M+H]+.

An example of retrieving 47

Obtaining 3-(4-dimethylcarbamoyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(2-methylthiazole-4-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 47 can be obtained by the method described in example a 1, a corresponding method, or a Combi is the situation and their standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methylthiazole, 4-dimethylcarbamodithioato and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,69 (3H, s)of 3.00 (3H, s), 3,14 (3H, s), to 6.95 (1H, d, J=8,8 Hz), 7,11 (1H, d, J=8,8 Hz), was 7.45 (2H, d, J=8.1 Hz), 7,56 (2H, d, J=8.1 Hz), to 7.64 (1H, s), 8,29 (1H, s)

MC (ESI) m/e: 498 [M+H]+.

Example obtain 48

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 48 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methoxymethanol, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,62 (3H, s), 3,44 (3H, s), 4,51 (2H, s)6,91 (1H, s), 6,93 (1H, d, J=8,4 Hz), 7,19 (1H, d, J=8,4 Hz), 7,26 (1H, d, J=8.0 Hz), to 7.77 (1H, DD, J=8.0 Hz, 2.4 Hz), 8,35 (1H, s), 8,61 (1H, d, J=2, 4 Hz)

MC (ESI) m/e: 472 [M+H]+.

An example of retrieving 49

Obtaining 3-(1-methyl-1H-tetrazol-5-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 49 can be obtained by the method described in example a 1, a corresponding method, or combination what s and their standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 5-mercapto-1-methyl-1,2,4-triazole and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,11 (3H, s), 7,11 (1H, d, J=3.2 Hz), 7,32 (1H, d, J=8,8 Hz), was 7.36 (1H, d, J=8,8 Hz), 7,52 (1H, d, J=3.2 Hz), 8,42 (1H, s)

MS (ESI) m/e: 419 [M+H]+.

Example of getting 50

Obtaining 3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 50 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-aminoanisole, 4-hydroxyethylidene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,91 (2H, t, J=4.6 Hz), of 4.05 (2H, t, J=4.6 Hz), 6,91 (1H, d, J=8,8 Hz), 6,92 (2H, d, J=8,4 Hz), 7,11 (1H, d, J=8,8 Hz), 7,22 (1H, d, J=l,5 Hz), 7,39 (2H, d, J=8,4 Hz), of 8.25 (1H, d, J=l,5 Hz), 8,29 (1H, s)

MC (ESI) m/e: 457 [M+H]+.

An example of retrieving 51

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 51 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard ways, with COI is whether the 3,6-dichloro-2-pyridineboronic acid, 3-aminoanisole, 4-dimethylaminoethylacrylate and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,43 (6N, (C), 2,85 (2H, t, J=5.5 Hz), of 4.12 (2H, t, J=5.5 Hz), make 6.90 (2H, d, J=8,8 Hz), 6,93 (1H, d, J=8,8 Hz), to 7.15 (1H, d, J=8,8 Hz), 7,24 (1H, s), 7,38 (2H, d, J=8,8 Hz), 8,30 (1H, s), scored 8.38 (1H, s)

MS (ESI) m/e: 484 [M+H]+.

An example of retrieving 52

Obtaining 3-(4-perpenicular)-6-phenoxy-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

To a solution (3 ml) 84 mg (0.2 92 mmol) of 3,6-dichloro-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide in N,N-dimethylformamide added phenol (135 mg, 1,43 mmol) and 540 mg (of 1.66 mol) of cesium carbonate, followed by stirring at a temperature of 120°C for 24 hours. To the reaction solution was added 1N. an aqueous solution of sodium hydroxide, then extracted with ethyl acetate. The organic layer is washed with water and saturated aqueous saline solution, dried and concentrated in vacuo. The resulting residue is purified by thin-layer chromatography on silica gel (hexane:ethyl acetate=4:1)to give 61 mg (yield: 61%) of 3-chloro-6-phenoxy-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide in a solid white color.

To a solution (2 ml) of the obtained 3-chlorinated in N,N-dimethylformamide added potassium carbonate (80 mg, 0,579 mmol) and 20 μl (0,188 mmol) of 4-portifino, followed by stirring at a temperature of 100°C for 16 hours. To p is a promotional solution was added water, followed by extraction with ethyl acetate and washing with saturated aqueous salt solution. After drying and concentrating, the resulting residue is purified by thin-layer chromatography on silica gel (hexane:ethyl acetate=4:1)to give 11 mg (yield: 32%) indicated in the title compound in the form of a solid white color.

1H-NMR (CDCl3) δ: is 2.37 (3H, s), to 6.58 (1H, s), make 6.90 (1H, d, J=9.0 Hz), 7,10-7.23 percent (6N, m), 7,46 (1H, d, J=7,8, and 7.8 Hz), a 7.62 (2H, m)

MC (ESI) m/e 438 [M+H]+.

The connection according to the example of getting 53 receive by way of example, receiving 52. Analytical data for this compound are given below.

Example of getting 53

Obtaining 3-(2-chlorophenethylamine)-6-amino-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 53 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide, 2-chlorobenzylamino and 3-mercapto-4-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.41 (3H, s), of 3.73 (3H, s)4,55 (2H, d, J=6.0 Hz), to 6.58 (1H, s), 6,92 (1H, d, J=9.3 Hz), 7,20 was 7.45 (5H, m), 8,32 (1H, s), 8,72 (1H, m)

MS (ESI) m/e: 472, 474 [M+H]+.

An example of retrieving 54

Obtain 3,6-bis(pyridine-2-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

To a solution (2 ml) 3,6-dig the PRS-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide, obtained by the method described in the example of obtaining 1, N,N-dimethylformamide, add 2-mercaptopyridine (24 mg, 0,205 mmol) and 68 g (0,492 mmol) of potassium carbonate, followed by stirring at a temperature of 100°C for 15 hours. To the reaction solution was added water, and then extracted with ethyl acetate and washed with saturated aqueous salt solution. After drying and concentrating, the resulting residue is purified by thin-layer chromatography on silica gel (chloroform:methanol=20:1)to give 15 mg (yield: 23%) specified in the connection header in a solid yellow color.

1H-HMP (CDCl3) δ: 2,39 (3H, s), to 6.58 (1H, s), 7,20-7,30 (2H, m), 7,40 (1H, d, J=8.6 Hz), 7,46 (1H, userd, J=8.1 Hz), 7,52 to 7.75 (4H, m), 8,55-8,65 (2H, m)

MS (ESI) m/e): 438 [M+H]+.

Compounds according to examples of the preparation 55-57 can be received by way of example, obtaining 54. Analytical data for these compounds are given below.

Example of getting 55

Obtain 3,6-bis(4-perpenicular)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 55 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide and 4-portifino.

1 3) δ: to 2.41 (3H, s), 6,59 (1H, s), 6,77 (1H, d, J=9.0 Hz), to 6.88 (1H, d, J=9.0 Hz), 7,09-7,20 (4H, m), 7,49-of 7.60 (4H, m)

MC (ESI) m/e: 472 [M+H]+.

An example of receiving 56

Obtain 3,6-bis(thiazole-2-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of receiving 56 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide and 2-mercaptothiazole.

1H-NMR (CDCl3) δ: 7,06 (1H, d, J=3.6 Hz), 7,27 (1H, d, J=8,8 Hz), 7,37 (1H, d, J=8,8 Hz), 7,54 (1H, d, J=3, 6 Hz), to 7.59 (1H, d, J=3.6 Hz), to 7.61 (1H, d, J=3.6 Hz), 7,98 (1H, d, J=3.6 Hz), 8,02 (1H, d, J=3,6 Hz)

MS (ESI) m/e): 436 [M+H]+.

An example of retrieving 57

Obtain 3,6-bis(5-methyl[1,3,4]thiadiazole-2-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 57 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide and 2-mercapto-5-methyl-1,3,4-thiazole.

1H-NMR (CDCl3) δ: of 2.86 (3H, s), 2.91 in (3H, s), 7,07 (1H, d, J=3.6 Hz), 7,44 (1H, d, J=8,8 Hz), 7,52 (1H, d, J=3.6 Hz), to 7.64 (1H, d, J=8,8 Hz)

MS (ESI) m/e): 466 [M+H]+.

An example of retrieving 58

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-methylthiazole-2-yl)-2-pyridinecarboxamide

Concentrated sulfuric acid (0,441 ml of 8.27 mmol) is added dropwise to a suspension of (35 ml) 3,86 g (32,2 mmol) of magnesium sulfate in dichloromethane and, after addition, the mixture is stirred at room temperature for 2 0 minutes. Then, at room temperature, to the reaction solution was added 750 mg (3,91 mmol) of 3,6-dichloro-2-pyridineboronic acid solution (10 ml) of 3.84 ml (40,2 mmol) tert-butyl alcohol in dichloromethane, and then intensively stirred at room temperature for 15 hours. While cooling with ice, to the reaction solution are added dropwise an aqueous solution (40 ml) 3.0 g of sodium carbonate and then stirred until the formation of homogeneous solution. The reaction solution is extracted with chloroform and the organic layer was washed with a saturated aqueous saline solution, dried and concentrated in vacuo. The resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=97:3), receiving 644 mg (yield: 66%) of tert-butyl-3,6-dichloro-2-pyridinecarboxylic in a solid white color.

To a solution (70 ml) 1.70 g (6,86 mmol) of ester obtained in N,N-dimethylformamide add 4-methoxythiophene (0,927 ml of 7.55 mmol) and 1.14 g (compared to 8.26 mmol) carbonatebuy at room temperature, followed by stirring for 1 hour. To the reaction solution was added chloroform, then washed with saturated aqueous sodium hydrogen carbonate and a saturated aqueous saline solution, dried and concentrated in vacuo. The resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=9:1)getting 743 mg (yield: 31%) of tert-butyl 6-chloro-3-(4-methoxybenzenesulfonyl)-2-pyridinecarboxylic in the form of a colorless oily substance.

To a solution (30 ml) 451 mg (1.28 mmol) of the obtained chlorinated compounds in N,N-dimethylformamide at room temperature, add 3-mercapto-1,2,4-triazole (258 mg, 2.55 mmol) and 353 mg (2.56 mmol) of potassium carbonate and the reaction solution is stirred at a temperature of 130°C for 10 hours. To the reaction solution was added chloroform, then washed with saturated aqueous sodium hydrogen carbonate and a saturated aqueous saline solution, dried and concentrated in vacuo. The resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=2:1)to give 264 mg (yield: 49%) of tert-butyl 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-2-pyridinecarboxylic in the form of a colorless oily substance.

To a solution (5.0 ml) 264 mg (0,633 mmol) of ester obtained in dichloromethane at room temperature add triperoxonane acid (2.0 ml) and the reaction solution per mesilat at room temperature for 1.5 hours. The reaction solution was concentrated in vacuo, getting 228 mg of 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-2-pyridineboronic acid as a pale yellow solid.

To a solution (1.0 ml) 5.9 mg (16 μmol) obtained carboxylic acid in dichloromethane at room temperature successively added 5-methylaminoethanol (3.2 mg, 29 μmol), 3.8 mg (27 μmol) of N-hydroxybenzotriazole and 5.4 mg (28 μmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and the reaction solution was stirred at room temperature for 3 hours. To the reaction solution was added saturated aqueous sodium hydrogen carbonate solution, then extracted with chloroform. The organic layer was washed with a saturated aqueous saline solution, dried and concentrated in vacuo. The resulting residue is purified column chromatography on silica gel (chloroform:methanol=95:5)to give 2.0 mg (yield: 15%) specified in the title compounds as a pale yellow solid.

1H-NMR (CDCl3) δ: 2,43 (3H, c), 3,86 (3H, s), 6,98 (2H, d, J=8,4 Hz), of 6.99 (1H, d, J=8,4 Hz), to 7.09 (1H, s), 7,19 (1H, d, J=8,4 Hz), 7,47 (2H, d, J=8,4 Hz), 8,32 (1H, s)

MS (ESI) m/e: 457 [M+H]+.

Compounds according to examples of the preparation 59-65 receive by way of example, receiving 58. Analytical data for these compounds are given below.

Example retrieve 59

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(isoxazol-3-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 59 can be obtained by the method described in example receiving 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 3-aminoisoquinoline.

1H-NMR (CDCl3) δ: 3,86 (3H, s), 6,98 (2H, d, J=8,4 Hz), of 6.99 (1H, d, J=8,4 Hz), 7,19 (1H, d, J=8,4 Hz), 7,30 (1H, s), 7,47 (2H, d, J=8,4 Hz), 8,31 (1H, s), to 8.41 (1H, s)

MS (ESI) m/e: 427 [M+H]+.

Example of getting 60

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,3,4]thiadiazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 60 can be obtained by the method described in example receiving 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 2-amino-1,3,4-thiadiazole.

1H-NMR (CDCl3) δ: 3,86 (3H, s), of 6.99 (2H, d, J=8.5 Hz), 7,03 (1H, d, J=8,4 Hz), 7.23 percent (1H, d, J=8,4 Hz), 7,47 (2H, d, J=8.5 Hz), to 8.45 (1H, s), cent to 8.85 (1H, s)

MC (ESI) m/e: 444 [M+H]+.

An example of retrieving 61

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ilal the Anil)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 61 can be obtained by the method described in example receiving 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 5-amino-1, 2,4-thiadiazole.

1H-NMR (CDCl3) δ: a 3.87 (3H, s)to 7.00 (2H, d, J=8,4 Hz), 7,01 (1H, d, J=8,4 Hz), 7,20 (1H, d, J=8,4 Hz), of 7.48 (2H, d, J=8.5 Hz), 7,80 (1H, s), at 8.36 (1H, s)

MS (ESI) m/e: 444 [M+H]+.

An example of retrieving 62

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylcarbonate-2-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 62 can be obtained by the method described in example receiving 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 4-acetyl-2-aminothiazole.

1H-NMR (CDCl3) δ: 2,63 (3H, s), 3,86 (3H, s), 6,98 (1H, d, J=8,8 Hz), 7,01 (2H, d, J=8,8 Hz), 7,22 (1H, d, J=8,8 Hz), 7,46 (2H, d, J=8,8 Hz), 7,86 (1H, s), with 8.33 (1H, s)

MS (ESI) m/e: 485 [M+H]+.

An example of retrieving 63

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyrimidine-4-yl)-2-pyridinecarboxamide

The connection according to the example of obtaining 63 may be p the Express way, described in the example of obtaining 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 4-aminopyrimidine.

1H-NMR (CDCl3) δ: 3,86 (3H, s), 6,98 (2H, d, J=8,8 Hz), 7,02 (1H, d, J=8,4 Hz), 7,22 (1H, d, J=8,4 Hz), 7,46 (2H, d, J=8,8 Hz), scored 8.38 (1H, DD, J=5,9, and 0.8 Hz), to 8.41 (1H, s), 8,65 (1H, d, J=5,9 Hz), 8,93 (1H, d, J=0.8 Hz)

MC (ESI) m/e 438 [M+H]+.

Example of getting 64

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridin-2-yl)-2-pyridinecarboxamide

The connection according to the example of a 64 may be obtained by the method described in example receiving 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 2-aminopyridine.

1H-NMR (CDCl3) δ: of 3.85 (3H, s), 6,97 (2H, d, J=8,8 Hz), of 6.99 (1H, d, J=8,8 Hz), 7,05 (1H, DD, J=8,5, and 4.5 Hz), 7,18 (1H, d, J=8,8 Hz), 7,46 (2H, d, J=8,8 Hz), 7,73 (1H, DDD, J=8,5, to 8.5, 1.5 Hz), 8,29 (1H, DD, J=4,5 and 1.5 Hz), 8,31 (1H, s), to 8.41 (1H, d, J=8,5 Hz)

MS (ESI) m/e: 437 [M+H]+.

Example getting 65

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-ethoxycarbonylmethyl-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 6 can be obtained by way described in the example of obtaining 58, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridinecarboxamide, 4-methoxythiophene, 3-mercapto-1,2,4-triazole and 2-amino-5-ethoxycarbonylmethyl.

1H-NMR (CDCl3) 6: 1,37 (3H, t, J=7.0 Hz), 3,86 (3H, s), 4,34 (2H, q, J=7.0 Hz), 6,98 (2H, d, J=8,8 Hz), 7,00 (1H, d, J=8.5 Hz), 7,20 (1H, d, J=8.5 Hz), 7,46 (2H, d, J=8,8 Hz), 8,11 (1H, s), at 8.36 (1H, s)

MS (ESI) m/e: 515 [M+H]+.

An example of retrieving 66

Obtaining 3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

To 152 mg (0,390 mmol) 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide obtained by the method described in example a 1, add anisole (and 0.40 ml, 0,390 mmol) and 5 ml triperoxonane acid and the reaction solution is stirred at a temperature of 60°C for 5 hours and then stirred overnight at room temperature. The reaction solution was concentrated in vacuo to obtain 3-thiol-derivative in the form of an orange oily substance.

To a solution (3 ml) obtained above 3-thiol-derived 2-propanol add 62 μl (1.10 mmol) of ethylene glycol, 141 mg (1,02 mmol) of potassium carbonate, 114 mg (0,560 mmol) 3-iodopyridine and 5.3 mg (0,030 mmol) of copper iodide, and the reaction solution stirred at temp is the temperature of 80° With during the night. The reaction solution is filtered through celite and the filtrate partitioned between chloroform and water. The organic layer is washed with water, dried and concentrated in vacuo. The resulting residue is purified by thin-layer chromatography on silica gel (hexane:ethyl acetate=1:1)to give 28 mg (yield: 21%) 6-chlorinated in the form of a solid pale yellow color.

Then to the solution (1 ml) 25 mg (0.22 mmol) of potassium tert-butylate in N,N-dimethylformamide added 22 mg (0.22 mmol) of 3-mercapto-1,2,4-triazole is added dropwise a solution (3 ml) 28 mg (0,080 mmol) obtained above 6-chlorinated in N,N-dimethylformamide and, after addition, the reaction solution is stirred at a temperature of 120°C for 2 hours. To the reaction solution was added water, and then extracted with chloroform. The organic layer is washed with water, dried and concentrated in vacuo. The resulting residue is purified by thin-layer chromatography on silica gel (chloroform:methanol=9:1)to give 12 mg (yield: 37%) indicated in the title compound in the form of a solid pale yellow color.

1N-ANR (CDCl3) δ: of 6.96 (1H, d, J=8,8 Hz), 7,05 (1H, d, J=3.6 Hz), 7,22 (1H, d, J=8,8 Hz), 7,40-the 7.43 (1H, m), 7,47 (1H, d, J=3.6 Hz), 7,87-of 7.90 (1H, m), 8,32 (1H, s), 8,64-8,66 (1H, m), 8,70-8,71 (1H, m)

MS (ESI) m/e): 414 [M+H]+.

Compounds according to examples of the preparation 67 and 68 receive by way of example according to the teachings 66. Analytical data for these compounds are given below.

An example of retrieving 67

Obtaining 3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example getting 67 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide, 6-methoxy-3-iodopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,00 (3H, s), 6.87 in (1H, d, J=8.7 Hz), 7,00-7,11 (2H, m), 7,26 (1H, d, J=8,4 Hz), 7,46 (1H, d, J=3.3 Hz), to 7.77 (1H, DD, J=2,4, and 8.7 Hz), 8,35 (1H, d, J=2.4 Hz), scored 8.38 (1H, s)

MC (ESI) m/e: 444 [M+H]+.

Example of getting 68

Obtaining 3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 68 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-N-(4-methoxybenzenesulfonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example obtain 1), 3-iodopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl 3) δ: 3,49 (3H, s), 4,56 (2H, s)6,94 (1H, s), 6,97 (1H, d, J=8,8 Hz), 7,27 (1H, d, J=8,8 Hz), the 7.43 (1H, DD, J=7,6 Hz, 3.3 Hz), to 7.93 (1H, d, J=7,6 Hz), scored 8.38 (1H, s)8,71 (1H, d, J=4,8 Hz), 8,77 (1H with)

MS (ESI) m/e: 458 [M+H]+.

Example of getting 69

Obtaining 3-phenoxymethyl-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

To a solution (50 ml) 3.50 g (14.0 mmol) of 2-cyano-3-tert-butyldimethylsilyloxy in chloroform add 3-chlormadinone acid (6,30 g, 21,0 mmol), followed by boiling under reflux overnight. To the reaction solution was added saturated aqueous sodium hydrogen carbonate solution, then extracted with chloroform and the organic layer washed with water, saturated aqueous sodium hydrogen carbonate and a saturated aqueous saline solution, then dried and concentrated. The resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=2:1)to give 1.50 g (yield: 41%) of N-oxide in a solid white color.

A solution (10 ml) 1.50 g (5,70 mmol) obtained N-oxide in phosphorus oxychloride is stirred at a temperature of 80°C for 1 hour. The reaction solution was concentrated in vacuo, to the residue is added saturated aqueous sodium hydrogen carbonate solution, then extracted with chloroform and the organic layer washed nassen the m aqueous solution of sodium bicarbonate and saturated aqueous salt solution. After drying and concentrating, the resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=2:1)to give 625 mg (yield: 58%) of 2-chloro-5-chloromethyl-6-cyanopyridine in the form of a solid white color.

To a solution (5 ml) to 50 mg (0.27 mmol) of 2-chloro-5-chloromethyl-6-cyanopyridine in acetonitrile add phenol (30 mg, 0.32 mmol) and 44 mg (0.32 mmol) of sodium bicarbonate, followed by stirring at room temperature for 8 hours and 30 minutes. To the reaction solution was added water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous saline solution, dried and concentrated in vacuo and the resulting residue purified thin-layer column chromatography (hexane:ethyl acetate=6:1)to give 61 mg (yield: 93%) of 2-chloro-6-cyano-5-phenoxyethylamine in a solid white color.

To a solution (5 ml), 61 mg (0,249 mmol) of the obtained 2-chloro-6-cyano-5-phenoxyethylamine in N,N-dimethylformamide added 3-mercapto-4-methyl-4H-1,2,4-triazole (44 mg, 0,380 mmol) and 52 mg (0,380 mmol) of potassium carbonate, followed by stirring at a temperature of 100°With during the night. To the reaction solution was added water, and then extracted with ethyl acetate and the organic layer washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous salt solution. After drying and it is tsentrirovannaja the resulting residue is purified thin-layer column chromatography (chloroform:methanol=10:1), getting 4.4 mg (yield: 5%) titrating derived.

To an ethanol solution (5 ml) 4.4 mg (0.014 mmol) obtained titrating derived type 1H. an aqueous solution (0.5 ml) of sodium hydroxide, then refluxed overnight. To the reaction solution was added for acidification of 1N aqueous solution of hcl, then extracted with ethyl acetate and the organic layer was washed with saturated aqueous salt solution. After drying and concentration, the solution (3 ml) of the obtained residue in dichloromethane successively added 3 mg (0,028 mmol) of 2-aminothiazole, 4 mg (0,030 mmol) of N-hydroxybenzotriazole and 6 mg (0,030 mmol) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, followed by stirring at room temperature over night. To the reaction solution was added saturated aqueous sodium hydrogen carbonate solution, then extracted with chloroform and the organic layer washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous salt solution. After drying and concentrating, the resulting residue is purified by thin-layer chromatography on silica gel (chloroform:methanol=10:1)to give 2.8 mg (yield: 47%) indicated in the title compound in the form of a solid white color.

1H-NMR (CDCl3) δ: with 3.79 (3H, s), 5,71 (2H, s), 6,97-7,02 (3H, m), 7,05 (1H,d, J=3.6 Hz), 7,30 (2H, t, J=7,6 Hz), 7,40 (1H, d, J=8,4 Hz), 7,54 (1H, d, J=3, 6 Hz), by 8.22 (1H, d, J=8,4 Hz)and 8.50 (1H, s)

MC (ESI) m/e: 425 [M+H]+.

The connection according to the example of getting 7 0 receive by way of example, receiving 69. Analytical data for the compounds are given below.

Example of getting 70

Obtaining 3-phenylsulfonyl-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 70 can be obtained by the method described in example getting 69, a corresponding method, or a combination of them and the standard methods, using 2-cyano-3-tert-butyldimethylsilyloxy, thiophenol, 3-mercapto-4-methyl-4H-1,2,4-triazole and 2-aminothiazole.

1H-NMR (CDCl3) δ: of 3.77 (3H, s), 4,74 (2H, s),? 7.04 baby mortality (1H, d, J=3.2 Hz), 7,20 (1H, d, J=8,4 Hz), 7, 24-7, 28 (5H, m), 7,53 (1H, d, J=3.2 Hz), 7,58 (1H, d, J=8,4 Hz), 8,48 (1H, s)

MC (ESI) m/e: 441 [M+H]+.

Example of getting 71

Obtaining 3-phenylmethyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

3-benzoyl-2-pyridylcarbonyl acid (2.0 g, 8,8 mmol) dissolved in 10 ml of methanol and, at room temperature was added 10 drops of concentrated sulfuric acid, and then refluxed in all day and night. After cooling, the methanol is evaporated, the ATEM is neutralized using a saturated aqueous solution of sodium bicarbonate. Carry out the extraction with chloroform, dried over sodium sulfate and concentrated, obtaining 2.0 g of methyl-3-benzoyl-2-pyridinecarboxylic in the form of a crude product.

Ester (2.0 g) dissolved in 10 ml of chloroform and added 3.57 g (20,7 mmol) m-chloroperoxybenzoic acid (mCPBA), and then refluxed in all day and night. After cooling, to the reaction solution was added saturated aqueous solution of sodium bicarbonate for alkalizing, and then extracted with chloroform. Dried over sodium sulfate and evaporated in vacuum, obtaining N-oxide in the form of a crude product. To the obtained crude product add 10 ml of phosphorus oxychloride, and then stirred at a temperature of 80°C for 2 hours. After cooling, neutralized with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. After drying over sodium sulfate and evaporation under vacuum, do the cleaning column chromatography on silica gel (ethyl acetate:hexane=1:2)to give 600 mg (yield: 26% (through three stages of purification)) methyl-3-benzoyl-6-chloro-2-pyridinecarboxylic.

Chlorinated (300 mg, 1.10 mmol) was dissolved in 15 ml of methanol and add 5 ml of 1N. the sodium hydroxide solution, followed by stirring at room temperature for 2 hours. After evaporation methanolate neutralize 1H. hydrochloric acid and extracted with chloroform. The chloroform extract is dried over sodium sulfate and evaporated in a vacuum, getting 285 mg (yield: 100%) of 3-benzoyl-6-chloro-2-pyridineboronic acid in the form of a crude product.

The result of the above carboxylic acid (285 mg, 1.1 mmol) dissolved in 10 ml of chloroform and added 109 mg (1.1 mmol) of 2-aminothiazole, 221 mg (1,64 mmol) of N-hydroxybenzotriazole and 229 mg (1.2 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, followed by stirring at room temperature all day and night. After adding distilled water, extracted with chloroform and dried over sodium sulfate. Obtained after evaporation of the solvent in vacuo the residue is purified column chromatography (ethyl acetate:hexane=1:2)to give 225 mg (yield: 60% (after two steps)of 3-benzoyl-6-chloro-N-(thiazol-2-yl)-2-pyridinecarboxamide.

Received higher chlorinated (170 mg, 0,495 mmol) dissolved in 3 ml of dimethylformamide and added 55 mg (0,544 mmol) of 3-mercapto-1,2,4-triazole and 171 mg (1,24 mmol) of potassium carbonate, followed by stirring at a temperature of 100°C for a whole day and night. The reaction solution is cooled, the dimethylformamide is evaporated from it and add distilled water, then neutralized with 1N. hydrochloric acid and extracted with chloroform. After drying over Sul is an atom of sodium and evaporation in vacuo the residue is purified column chromatography on silica gel (methanol:chloroform=1:10), getting 101 mg (yield: 50%) of 3-benzoyl-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide.

The above ketone (70 mg, 0,172 mmol) suspended in 5 ml of methanol, add a 12.7 mg (0,343 mmol) of sodium borohydride, and then stirred at room temperature for 30 minutes and the solvent is evaporated. To the obtained residue, add 99 mg (0,853 mmol) of triethylsilane and 5 ml triperoxonane acid, followed by stirring at a temperature of 60°C for 1 hour. After concentration the residue is partitioned between chloroform and saturated aqueous sodium hydrogen carbonate and the chloroform layer is dried over sodium sulfate. The residue obtained after evaporation of the solvent, purified by thin-layer chromatography on silica gel twice (methanol:chloroform=1:8 ethyl acetate:acetone=2:1)to give 13.5 mg (yield: 20%) specified in the connection header.

1H-NMR (CDCl3) δ: 4,63 (2H, s), of 6.99 (1H, d, J=3.6 Hz), 7.18 in-7,29 (5H, m), 7,38 (1H, d, J=8,4 Hz), 7,41 (1H, DD, J=3.6 Hz), was 7.45 (1H, d, J=8,4 Hz), with 8.33 (1H, s)

MC (ESI) m/e: 395 [M+H]+.

Example of getting 72

Obtaining 3-(4-performer)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example getting 72 can be obtained by the method described in example getting 71, a corresponding method, or a Combi is the situation and their standard methods, using 3-(4-perbenzoic)-2-pyridineboronic acid, 2-aminothiazole and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,60 (2H, s), 6,94-6,98 (2H, m), 7,01 (1H, d, J=3.6 Hz), 7,14-7,17 (2H, m), 7,40-7,46 (3H, m), 8,35 (1H, s)

MC (ESI) m/e: 413 [M+H]+.

Example of getting 73

Obtaining 3-(4-dimethylaminocarbonylmethyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 73 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-dimethylaminomethylphenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,39 (6H, c), 2,68 (2H, m), 2,84 (2H, m), 7,00-7,05 (2H, m), 7,18 (1H, d, J=8.7 Hz), 7,28 (2H, d, J=8,4 Hz), 7,41-7,58 (3H, m), 8,32 (1H, s)

MS (ESI) m/e: 484 [M+H]+.

Example of getting 74

Obtaining 3-(4-dimethylaminomethylphenol)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 74 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-dimethylaminomethyl is Nola and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.23 (6H, c)of 6.96 (1H, d, J=8,8 Hz), 7,00 (1H, d, J=3.6 Hz), 7,11 (1H, d, J=8,8 Hz), 7,34 (2H, d, J=8.0 Hz), the 7.43 (1H, d, J=3.6 Hz), 7,46 (2H, d, J=8.0 Hz), 8,29 (1H, s)

MS (ESI) m/e: 470 [M+H]+.

Example of getting 75

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-4-yl)-2-pyridinecarboxamide

The compound according to example getting 75 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 4-aminothiazole, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.85 (3H, s), of 6.96 (2H, d, J=8,8 Hz), 6,98 (1H, d, J=8,8 Hz), to 7.15 (1H, d, J=8,8 Hz), 7,46 (2H, d, J=8,8 Hz), of 7.90 (1H, d, J=2.4 Hz), a 8.34 (1H, s), 8,61 (1H, d, J=2.4 Hz)

MS (ESI) m/e: 443 [M+H]+.

Example of getting 76

Obtaining 3-(4-dimethylallyltranstransferase)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 76 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-dimethylcarbamodithioato and 3-mercapto-1,2,4-triazole.

1H-NMR CDCl 3) δ: 2,99 (3H, s)to 3.09 (3H, c), to 4.73 (2H, c), of 6.99 (2H, d, J=8,8 Hz), 7,01-7,03 (1H, m), 7,03 (1H, d, J=3.6 Hz), 7,19 (2H, d, J=8,4 Hz), was 7.45 (2H, d, J=8,8 Hz), 7,46 (2H, d, J=3.6 Hz), 8,30 (1H, C)

MS (ESI) m/e: 514 [M+H]+.

Example of getting 77

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-hydroxyethylthio-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 77 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-hydroxymethylimidazole, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,90 (2H, t, J=4,8 Hz), 3,83 (3H, s), 3,90 (2H, t, J=4,8 Hz), of 6.65 (1H, s), to 6.95 (2H, d, J=8.0 Hz), 6,97 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=8,8 Hz), the 7.43 (2H, d, J=8.0 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 487 [M+H]+.

An example of retrieving 78

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(5-hydroxy-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example getting 78 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-hydroxythiophenol and 5-hydroxy-3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.65 (3H, c), 6,98 is 7.50 (5H, m), 7,82 (1H, m)8,64 (1H, users)

MS (ESI) m/e: 444 [M+H]+.

Example of getting 79

Obtaining 3-(6-methoxycarbonylmethyl-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 79 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example a 1), 5-iodine-3-ethoxycarbonylpyrimidine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,01 (3H, c), 7,03 (1H, d, J=7,6 Hz), 7,05 (1H, d, J=3.6 Hz), 7,24 (1H, d, J=7,6 Hz), 7,47 (1H, d, J=3.6 Hz), 8,00 (1H, m), 8,16 (1H, d, J=8.0 Hz), with 8.33 (1H, c), 8,79 (1H, m)

MS (ESI) m/e: 472 [M+H]+.

Example of getting 80

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 80 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-1,2,4-thiadiazole, 4-dimethylaminoethoxy is OpenAL and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,42 (6H, s)2,84 (2H, t, J=5,1 Hz), of 4.13 (2H, t, J=5,1 Hz), of 6.96 (2H, d, J=8,4 Hz), 7,00 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=8,8 Hz), the 7.43 (2H, d, J=8,4 Hz), 8,35 (1H, s)

MS (ESI) m/e: 501 [M+H]+.

Example of getting 81

Obtaining 3-(pyrimidine-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 81 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example a 1), 5-iodopyrimidine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 6.95 (1H, d, J=8,4 Hz), 7,03 (1H, d, J=3.6 Hz), 7,22 (1H, d, J=8,4 Hz), 7,44 (1H, d, J=3.6 Hz), with 8.33 (1H, c), 8,82 (2H, c), 9,20 (1H, c)

MS (ESI) m/e: 415 [M+H]+.

Example of getting 82

Obtaining 3-(6-hydroxymethyluracil-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 82 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-hydroxyethylidene the a and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: a 4.86 (2H, s), 7,01 (1H, d, J=9,2 Hz), 7,07 (1H, d, J=3.2 Hz), 7,28 (1H, d, J=9,2 Hz), 7,41 (1H, d, J=7,6 Hz), 7,52 (1H, d, J=3.2 Hz), of 7.90 (1H, m), 8,42 (1H, c), a total of 8.74 (1H, m)

MS (ESI) m/e: 444 [M+H]+.

Example of getting 83

Obtain 3-[4-(1-methylpyrrolidine-3-yloxy)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 83 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-(1-methylpyrrolidine-3-yl)thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 1,90-to 1.98 (1H, m)to 2.35 (3H, c), of 2.25 to 2.35 (2H, m), 2,43-2,47 (1H, m), 2,80-and 2.83 (2H, m), 4,78-is 4.85 (1H, m), 6,85 (2H, d, J=8,4 Hz), to 6.95 (1H, d, J=8,8 Hz), 7,00 (1H, d, J=3.6 Hz), 7,12 (1H, d, J=8,8 Hz), 7,38 (2H, d, J=8,4 Hz), 7,42 (1H, d, J=3.6 Hz), 8,29 (1H, s)

MS (ESI) m/e: 512 [M+H]+.

Example of getting 84

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 84 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-1,2,4-tied is asola, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.65 (3H, s), 7,01 (1H, d, J=8.6 Hz), 7,26 (1H, d, J=8.6 Hz), 7,30 (1H, d, J=8.0 Hz), 7,78 (1H, DD, J=8.0 a, 2,2 Hz), 8,35 (1H, s), 8,42 (1H, c)8,64 (1H, d, J=2.2 Hz)

MS (ESI) m/e: 429 [M+H]+.

An example of retrieving 85

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The compound according to example getting 85 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-1,2,4-thiadiazole, 4-dimethylaminoethylacrylate and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,40 (6H, s), 2,62 (6H, s), of 2.81 (2H, t, J=5.5 Hz), of 4.12 (2H, t, J=5,1 Hz), of 6.96 (2H, d, J=8.5 Hz), 6,98 (1H, d, J=8.5 Hz), 7,20 (1H, d, J=8.5 Hz), 7,42 (2H, d, J=8.5 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 515 [M+H]+.

An example of retrieving 86

Obtaining 3-(1-hydroxy-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example getting 86 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridylcarbinol is islote, 2-aminothiazole, 3-mercapto-6-methyl-1-oksipiridina and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,60 (3H, c), 7,06 (1H, d, J=3.2 Hz), 7,12 (1H, d, J=8,4 Hz), 7,32 (1H, d, J=8,4 Hz), 7,39-7,39 (2H, m), 7,51 (1H, d, J=3.2 Hz), 8,44 (1H, s), 8,51 (1H, users)

MS (ESI) m/e: 446 [M+H]+.

Example of getting 87

Obtaining 3-(4-diethylaminoethylcellulose)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 87 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-diethylaminoethylamine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 1.14 (6H, t, J=7,6 Hz), 2,73 (4H, q, J=7,6 Hz)to 2.99 (2H, t, J=6.0 Hz), 4,14 (2H, t, J=6.0 Hz), of 6.99 (2H, d, J=8,8 Hz), 7,01 (1H, d, J=8,4 Hz), 7,07 (1H, d, J=4.0 Hz), 7,18 (1H, d, J=8,4 Hz), 7,46 (2H, d, J=8,8 Hz), 7,49 (1H, d, J=4.0 Hz), at 8.36 (1H, c)

MS (ESI) m/e: 528 [M+H]+.

Example of getting 88

Obtaining 3-(4-pyrrolidinylcarbonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 88 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, using the receiving 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-pyrrolidinecarboxamido and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 1,80-1,90 (4H, m), 2.70 height is 2.80 (4H, m), to 3.02 (2H, t, J=5,2 Hz), 4,18 (2H, t, J=5,2 Hz), to 6.95 (2H, d, J=8,8 Hz), 6,97 (1H, d, J=8,4 Hz), 7,02 (1H, d, J=3.6 Hz), 7,17 (1H, d, J=8,4 Hz), 7,42 (2H, d, J=8,8 Hz), was 7.45 (1H, d, J=3.6 Hz), 8,29 (1H, c)

MS (ESI) m/e: 526 [M+H]+.

Example of getting 89

Obtaining 3-(6-dimethylaminoethoxide-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 89 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 3-mercapto-6-dimethylaminopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.41 (6H, s), 2,82 (2H, t, J=5.6 Hz), 4,48 (2H, t, J=5.6 Hz), to 6.80 (1H, d, J=8,4 Hz), 6,98 (1H, d, J=8,4 Hz), 7,03 (1H, d, J=3.6 Hz), 7.23 percent (1H, d, J=8,4 Hz), 7,47 (1H, d, J=3.6 Hz), 7,63 (1H, DD, J=2,4, and 8.4 Hz), 7,27 (1H, d, J=2.4 Hz), at 8.36 (1H, c)

MS (ESI) m/e: 501 [M+H]+.

Example of getting 90

Obtaining 3-(pyrazole-4-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 90 can be obtained by the method described in example getting 66, a corresponding method, or comb the nation and their standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example obtain 1), 4-moderate and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 7,07 (1H, d, J=3.6 Hz), 7,18 (1H, d, J=8,4 Hz), 7,25 (1H, d, J=8,4 Hz), 7,49 (1H, d, J=3.6 Hz), of 7.70 (2H, c), 8,35 (1H, c)

MS (ESI) m/e: 403 [M+H]+.

Example of getting 91

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 91 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 4-dimethylaminoethylacrylate and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: is 2.37 (6H, c), 2,61 (3H, s), 2,80 (2H, t, J=5.6 Hz), of 4.12 (2H, t, J=5.6 Hz), 7,00 (2H, d, J=8,4 Hz), 7,02 (1H, d, J=8,8 Hz), 7,22 (1H, d, J=8,8 Hz), was 7.45 (2H, d, J=8,4 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 515 [M+H]+.

Example of getting 92

Obtaining 3-(4-carbamoyltransferase)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 92 can be obtained by the method described in example receipt is 1, the corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-carbamoyltransferase and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,48 (2H, c), to 6.95 (1H, d, J=8,4 Hz), 6,98 (2H, d, J=8,8 Hz), 7,02 (1H, d, J=3.6 Hz), 7,13 (1H, d, J=8,4 Hz), 7,44 (1H, d, J=3.6 Hz), was 7.45 (2H, d, J=8,8 Hz), with 8.33 (1H, s)

MS (ESI) m/e: 486 [M+H]+.

Example of getting 93

Obtain 3-(5-bromo-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 93 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 5-bromo-3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.72 (3H, s), 7,00 (1H, d, J=8,4 Hz), 7,05 (1H, d, J=3.6 Hz), 7,22-7,24 (1H, m), of 7.48 (1H, d, J=3.6 Hz), 8,01 (1H, d, J=2.0 Hz), with 8.33 (1H, s), charged 8.52 (1H, d, J=2.0 Hz)

MS (ESI) m/e: 505, 507 [M+H]+.

Example of getting 94

Obtain 3-[4-(2-hydroxyethylaminomethyl)]-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 94 can be obtained by the method described in example a 1,a corresponding method, or a combination of them and the standard ways, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methylthiazole, 4-(2-hydroxyethyl)thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,61 (3H, c), only 2.91 (2H, t, J=6.8 Hz), a-3.84 (2H, t, J=6.8 Hz), 7,07 (1H, d, J=8,4 Hz), 7,21 (1H, d, J=8,4 Hz), 7,35 (2H, d, J=8.0 Hz), of 7.48 (2H, d, J=8.0 Hz), at 8.36 (1H, s)

MS (ESI) m/e: 472 [M+H]+.

Example obtain 95

Obtain 3-[4-(2-hydroxyethylaminomethyl)]-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The compound according to example getting 95 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 4-(2-hydroxyethyl)thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,59 (3H, c)at 2.59 (3H, s)to 2.94 (2H, t, J=6.4 Hz), of 3.94 (2H, t, J=6.4 Hz), 7,03 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=8,8 Hz), 7,34 (2H, d, J=8.0 Hz), 7,49 (2H, d, J=8.0 Hz)

MS (ESI) m/e: 486 [M+H]+.

An example of retrieving 96

Obtaining 3-(pyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The compound according to example getting 96 can be obtained by the method described in example a 1, a corresponding method, or a combination of them the standard way, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,61 (3H, c), of 7.00 (1H, d, J=8,8 Hz), 7,29 (1H, d, J=8,8 Hz), 7,41-7,44 (1H, m), 7,88-to $ 7.91 (1H, m), to 8.41 (1H, c), 8,71-8,73 (1H, m), 8,76-8,77 (1H, m)

MS (ESI) m/e: 429 [M+H]+.

Example of getting 97

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 97 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,62 (3H, c), of 2.64 (3H, s), 7,02 (1H, d, J=8.0 Hz), 7,25 (1H, d, J=8.0 Hz), 7,31 (1H, d, J=8.0 Hz), 7,78 (1H, DD, J=1.6 Hz, 8.0 Hz), 8,35 (1H, s), at 8.60 (1H, d, J=1,6 Hz)

MS (ESI) m/e: 443 [M+H]+.

An example of retrieving 98

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[5,4-b]pyridine-2-yl)-2-pyridinecarboxamide

The compound according to example getting 98 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard with osobov, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazolo[5,4-b]pyridine, 4-dimethylaminoethylacrylate and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,43 (6H, c), 2,70-is 2.88 (2H, m), 4,08-to 4.14 (2H, m), to 6.88 (2H, d, J=8,4 Hz), 6.89 in-6,93 (1H, m), 7,13 (1H, d, J=8,8 Hz), 7,31-to 7.35 (1H, m), 7,38 (2H, d, J=8,8 Hz), of 7.96 (1H, d, J=8,4 Hz), of 8.37 (1H with), 8,44 (1H, d, J=4.0 Hz)

MS (ESI) m/e: 551 [M+H]+.

Example of getting 99

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The compound according to example getting 99 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,60 (3H, c), 2,61 (3H, c)to 3.64 (3H, c), of 7.00 (1H, d, J=8,8 Hz), 7,20 and 7.36 (1H, m), 7,29 (1H, d, J=8.0 Hz), to 7.77 (1H, DD, J=2,4, 8.0 Hz), 8,63 (1H, d, J=2.4 Hz)

MS (ESI) m/e: 457 [M+H]+.

Example 100

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,5]thiadiazole-3-yl)-2-pyridinecarboxamide

The compound according to example 100 can be obtained by the method described in example a 1, corresponding with the particular or a combination of them and the standard ways, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1,2,5-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,63 (3H, s), of 6.99 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=8,8 Hz), 7,29 (1H, d, J=8.1 Hz), 7,78 (1H, DD, J=8,1, 2.2 Hz), of 8.37 (1H, s), at 8.60 (1H, d, J=2.2 Hz), 9,38 (1H, c)

MS (ESI) m/e: 429 [M+H]+.

An example of retrieving 101

Obtaining 3-(2,3-dihydrobenzofuran-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example a 1), 5-iodine-2,3-dihydrobenzofuran and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,26 (2H, t, J=8,8 Hz), of 4.66 (2H, t, J=8,8 Hz)6,86 (1H, d, J=8.0 Hz), 7,02 (1H, d, J=3.2 Hz), 7,06 (1H, d, J=8,8 Hz), 7,22 (1H, d, J=8,8 Hz), 7,31 (1H, d, J=8.0 Hz), and 7.5 (1H, users), was 7.45 (1H, d, J=3.2 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 455 [M+H]+.

Example of getting 102

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methoxy[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 102 can be obtained by the method described in p is the iMER get 1, the corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methoxy-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.65 (3H, c), 4,08 (3H, c), 6,90-7,05 (1H, m), 7,10-7,30 (2H, m), 7,70-7,80 (1H, m), 8,39 (1H, c), 8,63 (1H, users)

MS (ESI) m/e: 459 [M+H]+.

Example of getting 103

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-cyclopropyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 103 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-cyclopropyl-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 0,90-1,20 (4H, m), of 2.20 to 2.35 (1H, m)of 2.64 (3H, s), of 6.99 (1H, d, J=8,8 Hz), 7,20-7,30 (2H, m), 7,76 (1H, DD, J=2,4, 8.0 Hz), scored 8.38 (1H, s), to 8.62 (1H, users)

MS (ESI) m/e: 469 [M+H]+.

Example of getting 104

Obtaining 3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 104 can be obtained by the method described in the example is a 1, the corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 4-dimethylaminoethylacrylate and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,41 (6H, c), 2,58 (3H, c)at 2.59 (3H, c), and 2.83 (2H, t, J=5.5 Hz), of 4.12 (2H, t, J=5.5 Hz), 6,91 (2H, d, J=8,8 Hz)6,94 (1H, d, J=8.6 Hz), 7,17 (1H, d, J=8.6 Hz), 7,40 (2H, d, J=8,8 Hz)

MS (ESI) m/e: 529 [M+H]+.

Example of getting 105

Obtaining 3-(2-herperidin-4-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 105 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example a 1), 2-fluoro-4-iodopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 6,95-7,10 (2H, m), 7,20-7,26 (2H, m), 7,30-7,42 (1H, m), 7,40-7,50 (1H, m), 8,10 compared to 8.26 (1H, m), scored 8.38-to 8.45 (1H, m)

MS (ESI) m/e: 432 [M+H]+.

Example of getting 106

Obtaining 3-(2-methoxypyridine-5-ylsulphonyl)-6-(2H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 106 can be the ü received by way described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide (which can be obtained by the method described in example a 1), 5-iodine-2-methoxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,10 (3H, c), 7,02 (1H, d, J=8,4 Hz), 7,06 (1H, d, J=3.6 Hz), 7,32 (1H, d, J=8,4 Hz)to 7.50 (1H, d, J=3.6 Hz), 8,39 (1H, s), 8,65 (2H, s)

MS (ESI) m/e: 445 [M+H]+.

Example of getting 107

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 107 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,62 (3H, c), of 2.64 (3H, s), of 6.99 (1H, d, J=8,8 Hz), 7,20-to 7.35 (2H, m), to 7.77 (1H, DD, J=2,0, 8.0 Hz), 8,35 (1H, c), 8,63 (1H, users)

MS (ESI) m/e: 443 [M+H]+.

Example of getting 108

Obtaining 3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

Connection is according to the example of getting 108 may be received by way described in the example of a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 4-hydroxyethylaminophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,63 (3H, c)to 3.99 (2H, m), 4,13 (2H, m), 7,00-was 7.08 (3H, m), 7,25 (1H, d, J=8,4 Hz), 7,49 (2H, d, J=8.7 Hz), at 8.36 (1H, c)

MS (ESI) m/e: 488 [M+H]+.

Example of getting 109

Obtaining 3-(4-diethylcarbamazine)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 109 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-diethylcarbamazine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,72 (6H, s), 7,02 (1H, d, J=3.6 Hz), 7,03 (1H, d, J=8.0 Hz), 7,20 (1H, d, J=8.0 Hz), 7,44 (1H, d, J=3.6 Hz), 7,66 (2H, d, J=8,4 Hz), 7,78 (2H, d, J=8,4 Hz), 8,31 (1H, s)

MS (ESI) m/e: 542 [M+H]+.

An example of retrieving 110

Obtaining 3-(6-cyclopropylamino-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The compound according to example getting 110 can be obtained by the method described in p is the iMER get 1, the corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 6-cyclopropyl-3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 0,70-to 1.38 (4H, m), 1,98-to 2.18 (1H, m), of 6.96-was 7.08 (2H, m), 7,46 (1H, d, J=3.2 Hz), of 7.70 (1H, DD, J=2.0 a, and 8.4 Hz), at 8.36 (1H, s), 8,56 (1H, d, J=2.0 Hz)

MS (ESI) m/e: 453 [M+H]+.

Example of getting 111

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(5-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 111 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 3-mercapto-6-methylpyridine and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.57 (3H, s)of 2.64 (3H, s), of 6.96 (1H, d, J=8,8 Hz), 7,02 (1H, d, J=3.6 Hz), 7,20 (1H, d, J=8,8 Hz), 7,25-7,29 (1H, m), 7,46 (1H, d, J=3, 6 Hz), 7,76 (1H, DD, J=2,4, a 7.6 Hz), 8,63 (1H, users)

MS (ESI) m/e): 442 [M+H]+.

Example of getting 112

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(pyrazole-4-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 112 can be obtained by the method described in example obtaining 1 that meet the current method, or a combination of them and the standard ways, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 3-mercapto-6-methylpyridine and 4-mercaptotetrazole.

1H-NMR (CDCl3) δ: 2,62 (3H, c), to 6.88 (1H, m), 7,05 (1H, m), 7,24 (1H, d, J=8,9 Hz), 7,30-to 7.68 (3H, m), 7,72 (1H, DD, J=1,1, 8,9 Hz), 7,76-of 7.82 (1H, m), at 8.60 (1H, d, J=1.1 Hz)

MS (ESI) m/e: 427 [M+H]+.

Example of getting 113

Obtaining 3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 113 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-hydroxy-1,2,4-thiadiazole, 6-ethoxy-3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 1.43 (3H, t, J=6.9 Hz), to 2.06 (3H, s), 4,42 (2H, q, J=6.9 Hz), 6,85 (1H, d, J=9.0 Hz), was 7.08 (1H, d, J=9.0 Hz), 7,29 (1H, d, J=9.0 Hz), 7,69 (1H, DD, J=9,0, 2,1 Hz), 8,31 (1H, d, J=2.1 Hz), of 8.37 (1H, c)

MS (ESI) m/e: 473 [M+H]+.

Example of getting 114

Obtaining 3-(4-dimethylaminocarbonylmethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 114 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and a hundred of the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-dimethylaminomethylphenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,72 (6H, s), 7,02 (1H, d, J=3.6 Hz), 7,03 (1H, d, J=8.0 Hz), 7,20 (1H, d, J=8.0 Hz), 7,44 (1H, d, J=3.6 Hz), 7,66 (2H, d, J=8,4 Hz), 7,78 (2H, d, J=8,4 Hz), with 8.33 (1H, s)

MS (ESI) m/e: 520 [M+H]+.

Example of getting 115

Obtain 3-(5-herperidin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 115 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 5-fluoro-3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,59 (3H, s), 7,02 (1H, d, J=8,8 Hz), 7,30 (1H, d, J=8,4 Hz), 7,60 to 7.75 (1H, m), to 8.41 (1H, s), 8,50-8,65 (2H, m)

MS (ESI) m/e: 447 [M+H]+.

Example of getting 116

Obtaining 3-(2,3-dihydrobenzofuran-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 116 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using the receiving 6-chloro-3-(4-methoxybenzenesulfonyl)-N-(3-methyl-1,2,4-thiadiazole-5-yl)-2-pyridinecarboxamide (which can be obtained by way described in the example of a 1), 5-iodine-2,3-dihydrobenzofuran and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,61 (3H, s)of 3.25 (2H, t, J=8,4 Hz)and 4.65 (2H, t, J=8,4 Hz), 6,85 (1H, d, J=8,4 Hz), 7,05 (1H, d, J=8,4 Hz), 7,06-7,33 (3H, m), 7,78 (1H, DD, J=2,4, 8.5 Hz), 8,31 (1H, c)

MS (ESI) m/e: 470 [M+H]+.

Example of getting 117

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]triazine-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 117 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1,2,4-triazine, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.84 (3H, c), to 6.95 (2H, d, J=8,8 Hz), 7,00 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=8,8 Hz), 7,44 (2H, d, J=8,8 Hz), 8,40 (1H, s), 8,63 (1H, d, J=2.4 Hz), 8,96 (1H, d, J=2.4 Hz)

MS (ESI) m/e: 439 [M+H]+.

Example of getting 118

Obtaining 3-(4-carboxyphenylazo)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 118 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridylcarbinol sour is you, 5-amino-3-methyl-1,2,4-thiadiazole, 4-carboxamidine and 3-mercapto-5-methyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.46 (3H, s), 2,52 (3H, s), 7,00 (1H, d, J=8,8 Hz), 7,13 (1H, d, J=8,8 Hz), 7,52 (2H, d, J=7.8 Hz), 8,01 (2H, d, J=8.0 Hz)

MC (ESI) m/e: 486 [M+H]+.

Example of getting 119

Obtaining 3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(pyrazin-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 119 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminopyrazine, 6-ethoxy-3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 1.43 (3H, t, J=6.9 Hz), to 4.41 (2H, q, J=6.9 Hz), 6,83 (1H, d, J=8.7 Hz), 7,06 (1H, d, J=8.7 Hz), 7,27 (1H, d, J=8.7 Hz), 7,69 (1H, m), 8,29-8, 35 (2H, m), 8,40 (1H, m), 8,42 (1H, s), 9,75 (1H, m)

MC (ESI) m/e: 453 [M+H]+.

Example obtain 120

Obtaining 3-(imidazo[1,2-a]pyridine-6-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The compound according to example getting 120 can be obtained by the method described in example getting 66, a corresponding method, or a combination of them and the standard methods, using 6-chloro-3-(4-methoxybenzenesulfonyl-N-(3-methyl-1,2,4-thiadiazole-5-yl)-2-pyridinecarboxamide (which can be obtained by way described in the example of a 1), 6-itemids[1,2-a]pyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (DMSO-d6) δ: 3,30 (3H, c), 7,10-7,40 (3H, m), 7,60-7,80 (2H, m), of 7.97 (1H, s), 8,60-8,80 (1H, m), 8,93 (1H, s)

MS (ESI) m/e: 468 [M+H]+.

Example of getting 121

Obtaining 3-(2-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 121 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-2-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,59 (3H, c), 2,62 (3H, s), at 6.84 (1H, d, J=8,8 Hz), 7,20-to 7.35 (2H, m), 7,80-a 7.92 (1H, m), 8,43 (1H, s), 8,60-8,68 (1H, m)

MS (ESI) m/e: 443 [M+H]+.

Example of getting 122

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazolo[4,5-b]pyridine-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 122 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazolo[4,5-b]pyridine, 4-methoxythiophene and 3 scoops is-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,88 (3H, c), 7,01 (2H, d, J=8,8 Hz), 7,03 (1H, d, J=8.0 Hz), 7,02-7,26 (1H, m)to 7.50 (2H, d, J=8,8 Hz), 8,23 (1H, d, J=8.0 Hz), charged 8.52 (1H, s), 8,59 (1H, c)

MS (ESI) m/e: 494 [M+H]+.

Example of getting 123

Obtain 3-(5-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 123 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-5-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,40 (3H, c), 2,60 (3H, s), of 6.99 (1H, d, J=8,4 Hz), 7,22-7,30 (1H, m), 7,71 (1H, c), 8,40 (1H, c), 8,55 (2H, m)

MS (ESI) m/e: 443 [M+H]+.

Example of getting 124

Obtaining 3-(4,4-diftormetilirovaniya)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(pyridin-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 124 may be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminopyridine, 4,4-differentlocations and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 6,62 (1H, t, J=7 Hz), 7,05 (1H, d, J=9.0 Hz), 7,20-7,30 (3H, m), 7,60 (2H, d, J=8.7 Hz), 8.30 to-8,43 (2H, m), to 8.41 (1H, users), 9,78 (1H, users)

MS (ESI) m/e: 474 [M+H]+.

An example of retrieving 125

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The compound according to example getting 125 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.64 (3H, s)to 3.89 (3H, c)6,91 (1H, m), 6,97 (1H, d, J=8,4 Hz), 7,17 and 7.36 (3H, m), 7,79 (1H, m), 8,31 (1H, c), 8,63 (1H, m)

MS (ESI) m/e: 425 [M+H]+.

Example of getting 126

Obtaining 3-(6-hydroxyethylidene-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 126 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 6-hydroxyethyl-3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.57 (3H, c), totaling 3.04 (2H, t, J=6,0 is C), of 3.97 (2H, t, J=6.0 Hz), 6,98 (1H, d, J=8,8 Hz), 7,20 (1H, d, J=8,8 Hz), 7,30 (1H, d, J=8.0 Hz), 7,78 (1H, DD, J=2,4, 8.0 Hz), 8,32 (1H, s), to 8.57 (1H, d, J=2.4 Hz)

MS (ESI) m/e: 473 [M+H]+.

Example of getting 127

Obtaining 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 127 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-mercapto-1-methyl-1H-[1,2]pyrazole, 4-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.85 (3H, s), 6.89 in (1H, users), 6,97 (1H, d, J=8.7 Hz), 7,11-7,21 (3H, m), 7,30 (1H, d, J=8.7 Hz), EUR 7.57 (2H, m), 8,35 (1H, c)

MS (ESI) m/e 428 [M+H]+.

Example of getting 128

Obtaining 3-(2-methylimidazo[1,2-a]pyridine-6-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 128 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 6-mercapto-2-methylimidazo[1,2-a]pyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (DMSO-d6) δ : of 2.34 (3H, c), of 2.50 (3H, s), 7,10-7,20 (2H, m), 7,28 (1H, d, J=8,4 Hz), 7,49 (1H, d, J=9,2 Hz), of 7.70 (1H, c), to 8.70 (1H, users), 8,83 (1H, s)

MS (ESI) m/e: 482 [M+H]+.

Example of getting 129

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-hydroxymethyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 129 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,59 (3H, c)and 4.65 (2H, s), 6,97 (1H, d, J=8,4 Hz), 7.23 percent (1H, d, J=8,4 Hz), 7,26 (1H, d, J=7,6 Hz), 7,74 (1H, DD, J=2.0 a, 7,6 Hz), a 8.34 (1H, s), 8,54 (1H, d, J=2.0 Hz)

MS (ESI) m/e: 459 [M+H]+.

An example of retrieving 130

Obtain 3-[4-(2-hydroxyethyl)phenylsulfanyl]-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The compound according to example getting 130 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 4-hydroxyethylidene and 3-mercapto-4-methyl-1,2,4-triazole.

H-NMR (CDCl3) δ: 2,61 (3H, c), with 2.93 (2H, t, J=6.4 Hz), and 3.72 (3H, s)to 3.92 (2H, t, J=6.4 Hz), 7,06 (1H, d, J=8,4 Hz), 7,11 (1H, d, J=8,4 Hz), 7,35 (2H, d, J=8.0 Hz), 7,47 (2H, d, J=8.0 Hz), scored 8.38 (1H, s)

MS (ESI) m/e: 486 [M+H]+.

Example of getting 131

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(5-hydroxy-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 131 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-6-methylpyridine and 5-hydroxy-3-mercapto-1,2,4-triazole.

1H-NMR (DMSO-d6) δ: 2,53 (3H, c), to 2.65 (3H, s), 7,13-7,71 (3H, m), 7,84-7,98 (1H, m), 8,43-8,63 (1H, m)

MS (ESI) m/e: 459 [M+H]+.

Example of getting 132

Obtaining 3-(1-methyl-1H-indazol-5-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 132 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 5-mercapto-1-methyl-1H-indazole and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.53 (3H, s), a 4.03 (3H, s), 6.87 in (1H, d, J=8,8 Hz), 7,06 (1H, d, J=8,8 Hz), 7,39 was 7.45 (2H, m), 7,94 (2H, m), of 8.27 (1H, c)

MS (ESI) m/e: 482 [M+H]+.

Example of getting 133

Obtaining 3-(3-methyl[1,2,4]triazolo[4,3-a]pyridine-7-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 133 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-mercapto-1,2,4-thiadiazole, 7-mercapto-3-methyl[1,2,4]triazolo[4,3-a]pyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (DMSO-d6) δ: 2,49 (3H, s)to 2.67 (3H, s), PC 6.82-6.87 in (1H, m), 7,19 (1H, d, J=8,8 Hz), EUR 7.57 (1H, d, J=8,8 Hz), 7,86 (1H, s), 8,35 (1H, d, J=7,2 Hz), 8,70-of 8.90 (1H, users)

MS (ESI) m/e: 483 [M+H]+.

Example of getting 134

Obtaining 3-(1-hydroxy-6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 134 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 3-mercapto-6-methyl-1-oxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.58 (3H, c), 2,61 (3H, s), 7,16 (1H, d, J=8,4 Hz), 7,32 (1H, d, J=8,4 Hz), 7,40 was 7.45 (2H, m), scored 8.38 (1H, c), 8,43 (1H, users)

MS (ESI) m/e: 459 [M+H]+.

Example of getting 135

Obtaining 3-(6-hydroxymethyluracil-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 135 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 6-hydroxymethyl-3-mercaptopyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,62 (3H, s), 4,80 (2H, s), 7,01 (1H, d, J=8,8 Hz), 7,26 (1H, d, J=8,8 Hz), 7,56 (1H, d, J=8.0 Hz), to $ 7.91 (1H, DD, J=8.0 Hz); 1.2 Hz), at 8.36 (1H, s), 8,65 (1H, d, J=1.2 Hz)

MS (ESI) m/e: 459 [M+H]+.

Example of getting 136

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 136 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 4-methoxythiophene and 3-mercapto-1,2,4-triazole

1H-NMR (CDCl3) δ: is 3.82 (3H, s), 3,83 (3H, s), to 6.80 (1H, d, J=2.4 Hz), 6,93 (1H, d, J=8,4 Hz)6,94 (2H, d, J=8,8 Hz), was 7.08 (1H, d, J=8,4 Hz), 7,25 (1H, d, J=2.4 Hz), the 7.43 (2H, d, J=8,8 Hz), 8,32 (1H, s)

MS (ESI) m/e: 440 [M+H]+.

Example of getting 137

Obtaining 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 137 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1H-[1,2]pyrazole, 4-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 6,87 (1H, users), 6,94 (1H, d, J=8,4 Hz), 7,12-to 7.18 (3H, m), 7,45-7,53 (3H, m), 8,30 (1H, c)

MS (ESI) m/e: 414 [M+H]+.

Example of getting 138

Obtaining 3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 138 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methylthiazole, 3-mercapto-6-methoxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,63 (3H, s), of 4.00 (3H,s), to 6.88 (1H, d, J=8.7 Hz), 7,07 (1H, d, J=8.7 Hz), 7,29 (1H, d, J=8.7 Hz), of 7.70 (1H, DD, J=8,7, and 2.1 Hz), 8,31-to 8.40 (2H, m)

MS (ESI) m/e: 459 [M+H]+.

Example of getting 139

Obtain 3-[4-(1H-imidazol-1-yl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide

The connection according to the example of getting 139 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 5-amino-3-methyl-1,2,4-thiadiazole, 4-(1H-imidazol-1-yl)thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.57 (3H, s), 7,03 (1H, d, J=8,8 Hz), 7,16 (2H, users), 7,31 (1H, users), of 7.48 (1H, d, J=8,4 Hz), the 7.65 (2H, d, J=8,4 Hz), 7,92 (1H, s), 8,32 (1H, s)

MS (ESI) m/e: 494 [M+H]+.

An example of retrieving 140

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The compound according to example getting 140 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1H-[1,2]pyrazole, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 6,86 (1H, d, J=2.6 Hz), 6,98 (2H, d, J=8,8 Hz), of 6.99 (1H, d,J=8,8 Hz), 7,17 (1H, d, J=8,8 Hz), 7,47 (2H, d, J=8,8 Hz)to 7.50 (1H, d, J=2.6 Hz), a 8.34 (1H, s)

MS (ESI) m/e: 426 [M+H]+.

Example of getting 141

Obtaining 3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 141 may be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-pyrazole, 3-mercapto-6-methoxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,81 (3H, c), of 3.95 (3H, s)6,76 (1H, d, J=2.4 Hz), to 6.80 (1H, d, J=8,4 Hz), 6,93 (1H, d, J=8,4 Hz), 7,10 (1H, d, J=8,4 Hz), 7,25 (1H, d, J=2.4 Hz), the 7.65 (1H, DD, J=8,4 Hz, 2.0 Hz), of 8.28 (1H, d, J=2.0 Hz), at 8.36 (1H, s), 10,11 (1H, s)

MS (ESI) m/e: 441 [M+H]+.

Example of getting 142

Obtaining 3-(6-ethoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 142 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-pyrazole, 3-mercapto-6-ethoxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ : of 1.43 (3H, t, J=6.9 Hz), a 3.87 (3H, s), 4,42 (2H, q, J=6.9 Hz), 6,83 (1H, d, J=8.7 Hz), 6,93 (1H, d, J=2.1 Hz), 7,02 (1H, d, J=8.7 Hz), 7,22 (1H, d, J=8.7 Hz), 7,32 (1H, d, J=2.1 Hz), 7,69 (1H, DD, J=of 8.7, 2.4 Hz), 8,25-8,39 (2H, m)

MS (ESI) m/e: 455 [M+H]+.

Example of getting 143

Obtaining 3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 143 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-pyrazole, 4-methoxybutyrophenone and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.45 (3H, s), 3,82 (3H, c), of 4.49 (2H, c), 6,83 (1H, d, J=2.0 Hz), of 6.96 (1H, d, J=8,8 Hz), to 7.09 (2H, d, J=8,8 Hz), 7,25 (1H, d, J=2.0 Hz), 7,40 (2H, d, J=7,6 Hz), 7,51 (2H, d, J=7,6 Hz), 8,31 (1H, c), 10,14 (1H, c)

MS (ESI) m/e: 440 [M+H]+.

Example of getting 144

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4,5-dimethylthiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 144 may be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4,5-dimethylthiazole, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: to 2.29 (3H, s), of 2.33 (3H, c), a 3.87 (3H, c), 6,98-7,03 (3H, m), 7,21 (1H, d, J=8.6 Hz), of 7.48 (2H, d, J=8.6 Hz), 8,29 (1H, c)

MS (ESI) m/e: 471 [M+H]+.

Examples of obtaining 145

Obtaining 3-(4-perpenicular)-6-(4,5-dimethyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 145 may be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-methoxymethanol, 4-portifino and 3-mercapto-4,5-dimethyl-1,2,4-triazole.

1H-NMR (CDCl3) δ: 2,60 (3H, s), 3,47 (3H, s), 3,62 (3H, s), 4,50 (2H, s), 6,93 (1H, s), 6,98 (1H, d, J=8,8 Hz), 7,07 (1H, d, J=8,8 Hz), 7,16 (2H, DD, J=8,8, 8,8 Hz), 7,53 (2H, DD, J=5,2, 8,8 Hz)

MS (ESI) m/e: 503 [M+H]+.

Example of getting 146

Obtaining 3-(4-(1-methoxyethyl)phenylsulfanyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 146 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-(1-methoxyethyl)thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl 3) δ: of 1.27 (3H, d, J=6.4 Hz), 3,30 (3H, s), 4,36 (1H, d, J=6.4 Hz), 7,03 (1H, d, J=3.6 Hz), 7,05 (1H, d, J=8,8 Hz), 7.23 percent (1H, d, J=8,8 Hz), 7,41 (2H, d, J=8.0 Hz), 7,47 (1H, d, J=3.6 Hz), 7,54 (2N, d, J=8.0 Hz), 8,35 (1H, s)

MC (ESI) m/e: 471 [M+H]+.

Example of getting 147

Obtaining 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-hydroxymethylimidazole-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 147 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-4-hydroxymethylimidazole, 4-portifino and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 4,60 (2H, s), at 6.84 (1H, s), 6,93 (1H, d, J=8,8 Hz), 7,06-7,16 (3H, m), 7,40-of 7.60 (2H, m), 8,31 (1H, s)

MS (ESI) m/e): 461 [M+H]+.

Example of getting 148

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(5-cryptomaterial-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 148 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino-5-cryptomaterial, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3

MS (ESI) m/e: 509 [M+H]+.

Example of getting 149

Obtaining 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-cryptomaterial-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 149 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, using 3, 6-dichloro-2-pyridineboronic acid, 2-amino-4-cryptomaterial, 4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.85 (3H, s), of 6.96-to 7.00 (3H, m), 7,17 (1H, d, J=8.0 Hz), 7,44-7,47 (3H, m), of 8.37 (1H, s)

MC (ESI) m/e: 511 [M+H]+.

Example of getting 150

Obtaining 3-(3-fluoro-4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 150 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 3-fluoro-4-methoxythiophene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.95 (3H, s), 7,01-7,06 (3H, m), 7.23 percent-to 7.32 (3H, m), 7,47 (1H, d, J=4.0 Hz), 8,32 (1H, s)

MC (ESI) m/e: 461 [M+H]+.

Example the floor is placed 151

Obtain 3-[4-(1,1-dimethyl-1-hydroxymethyl)phenylsulfanyl]-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 151 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-aminothiazole, 4-(1,1-dimethyl-1-hydroxymethyl)thiophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 1,63 (6N, (C), of 6.99-7.03 is (2H, m), 7,18 (1H, d, J=8,4 Hz), 7,39 (1H, d, J=3, 6 Hz), 7,51 (2H, d, J=8,4 Hz), 7,58 (2H, d, J=8,4 Hz), 8,30 (1H, s)

MS (ESI) m/e: 471 [M+H]+.

Example of getting 152

Obtaining 3-(3,4-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 152 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 3,4-Divertimento and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3S: of 3.84 (3H, s), PC 6.82 (1H, d, J=2.0 Hz), 6,94 (1H, d, J=8,8 Hz), to 7.15 (1H, d, J=8,8 Hz), 7,20-7,41 (4H, m), with 8.33 (1H, s)

MC (ESI) m/e: 446 [M+H]+.

Example of getting 153

Obtaining 3-(3,5-differentsurfaces)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 153 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 3,4-Divertimento and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,81 (3H, s), for 6.81 (1H, d, J=2,8 Hz), 6,83-of 6.90 (1H, m),? 7.04 baby mortality-7,06 (2H, m), 7,16 (1H, d, J=8,8 Hz), 7,27 (1H, d, J=2,8 Hz), of 8.27 (1H, s)

MS (ESI) m/e: 446 [M+H]+.

Example of getting 154

Obtaining 3-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 154 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 5-mercapto-1-methyl-1,3-dihydroindol-2-it 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3.15 in (3H, s), of 3.48 (2H, s), 3,76 (3H, s), of 6.75 (1H, d, J=2.4 Hz), 6,83 (1H, d, J=8.0 Hz), to 6.88 (1H, d, J=8,8 Hz), 7,02 (1H, d, J=8,8 Hz), 7.23 percent (1H, d, J=2.4 Hz), 7,31 (1H, d, J=1.6 Hz), 7,41 (1H, DD, J=8.0 a, 1,6 Hz), by 8.22 (1H, s)

MS (ESI) m/e: 479 [M+H]+

Example of getting 155

Obtaining 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]triazolopyrimidine-2-yl)-2-pyridinecarboxamide

The connection according to the example of getting 155 may be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 2-amino[1,2,4]triazolopyridine, 3-mercapto-6-methylpyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 2.58 (3H, s), 6,93 (1H, d, J=8,8 Hz), 7,01 (1H, t, J=6.4 Hz), 7,16 (1H, d, J=8,8 Hz), 7,24 (1H, d, J=8.0 Hz), 7,51-of 7.60 (2H, m), 7,73 (1H, DD, J=8.0 a, 2,4 Hz), 8,32 (1H, s), 8,53 (1H, s), 8,60 (1H, d, J=6,4 Hz)

MC (ESI) m/e: 462 [M+H]+.

Example of getting 156

Obtaining 3-(4-ethoxymethylenemalonic)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 156 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 4-ethoxymethylene and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 1.28 (3H, t, J=6.8 Hz), of 3.60 (2H, q, J=6.8 Hz), 3,83 (3H, s), of 4.54 (2H, s), 6,85 (1H, d, J=2.0 Hz), 6,98 (1H, d, J=8,8 Hz), 7,10 (M, d, J=8,8 Hz), 7,26 (1H, d, J=2.0 Hz), 7,41 (2H, d, J=8.0 Hz), 7,51 (2H, d, J=8.0 Hz), 8,31 (1H, s)

MS (ESI) m/e: 468 [M+H]+.

Example of getting 157

Obtaining 3-(6-oxo-1,6-dihydropyridines-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 157 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 3-mercapto-6-methoxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: 3,86 (3H, s), 6,63 (1H, d, J=9.3 Hz), 6,85 (1H, d, J=2.1 Hz), 7,21 (1H, d, J=9.0 Hz), 7,27 (1H, d, J=9.0 Hz), 7,33 (1H, m), 7,45 (1H, userd, J=9,3 Hz), 7,58 (1H, d, J=2.1 Hz), 8,35 (1H, s)

MC (ESI) m/e: 427 [M+H]+.

Example of getting 158

Obtaining 3-(6-methoxypyridine-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 158 can be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 3-mercapto-6-methoxypyridine and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3 ) δ: 4,00 (3H, s), 6,84-6,94 (2H, m), 7,02 (1H, d, J=9.0 Hz), 7,22 (1H, d, J=9.0 Hz), 7,52 (1H, m), of 7.70 (1H, m), 8,31-to 8.40 (2H, m)

MC (ESI) m/e: 427 [M+H]+.

Example of getting 159

Obtaining 3-(4-hydroxyethylaminomethyl)-6-(4-methyl-4H-[1,2,4]triazole-3-ylsulphonyl)-N-(1-methyl-1H-[1,2]pyrazole-3-yl)-2-pyridinecarboxamide

The connection according to the example of getting 159 may be obtained by the method described in example a 1, a corresponding method, or a combination of them and the standard methods, with the use of 3,6-dichloro-2-pyridineboronic acid, 3-amino-1-methyl-1H-[1,2]pyrazole, 4-hydroxyethylaminophenol and 3-mercapto-1,2,4-triazole.

1H-NMR (CDCl3) δ: of 3.73 (3H, s), 3,85 (3H, s), of 4.00 (2H, m), 4,13 (2H, m), 6.87 in (1H, d, J=2,l Hz), 6,95-7,06 (3H, m), 7.24 to 7,31 (2H, m), 7,46 (2H, d, J=8.7 Hz), to 8.41 (1H, s)

MS (ESI) m/e: 484 [M+H]+.

Listed below are the methods for obtaining the compounds used for producing compounds according to the present invention, in the form of reference examples 1-6.

Reference example 1

Getting 5-methoxymethyl-3-mercapto-1,2,4-triazole

Methoxyacetanilide (2,82 g; is 0.023 mol) are added to a solution (15 ml) of 2.09 g (0,0230 mol) of thiosemicarbazide in pyridine, followed by stirring for one whole day and night at room temperature. The reaction solution is concentrated and to the residue add 10 m is of methanol and 8 ml of 25 wt.%-aqueous methanolic solution of sodium methylate, then refluxed for a whole day and night. After cooling to room temperature the solvent is evaporated and to the residue for acidification add concentrated hydrochloric acid. Separated solid is filtered off, washed with distilled water and dried, obtaining 1.0 g (yield: 33%) specified in the connection header.

1H-NMR (DMSO) δ: 3,24 (3H, s), the 4.29 (2H, s)

MC (ESI) m/e: 146 [M+H]+.

Reference example 2

Obtaining 2-amino-4-methoxymethanol

To a solution (120 ml) of 13.4 g (106 mmol) of dichloroacetone add 8.06 g (106 mmol) of thiourea, and then stirred at a temperature of 55°C for 3 hours. The reaction solution is concentrated and the obtained solid substance of white color add 200 ml of methanol and 15.1 g (125 mmol) of magnesium sulfate, and then refluxed for 3 days. The reaction mixture was filtered through celite and the filtrate is concentrated and partitioned between chloroform and saturated aqueous sodium bicarbonate. Then the organic layer is dried and concentrated, the obtained residue is purified column chromatography on silica gel (ethyl acetate) and crystallization from a mixed solvent consisting of hexane and ethyl acetate (4:1), receiving 6,59 g (yield: 43%) indicated in the title the connection information in the form of a solid yellow color.

1H-HMP (CDCl3) δ: 3,44 (3H, s), 4,34 (2H, s), of 6.45 (1H, s)

MS (ESI) m/e: 145 [M+H]+.

Reference example 3

Getting 4-acetyl-2-aminothiazole To a solution (30 ml) of 1.30 g (5,14 mmol) of 2-(tert-butyloxycarbonyl)-4-carboxylate in N, N-dimethylformamide successively added 660 mg (6,77 mmol) N,O-dimethylhydroxylamine, 1,40 ml (9,96 mmol) of triethylamine, 1.10 g (8,14 mmol) of N-hydroxybenzotriazole and 1.60 g (8,35 mmol) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, then stirred at room temperature for 5 days. The reaction solution is concentrated and to the residue is added ethyl acetate and the mixture is washed with 1N. an aqueous solution of hcl, water and saturated aqueous solution of sodium chloride, dried and concentrated in vacuo, receiving 1.35 g (yield: 91%) of the amide compound in the form of an oily substance. Solution (40 ml) 920 g (3,20 mmol) of the obtained amide compound in tetrahydrofuran is cooled to totemperature -78°and to it add to 18.0 ml (18.0 mmol) of a solution metallice in diethyl ether, then stirred for 7 days. To the reaction solution was added saturated aqueous solution of ammonium chloride, then extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated, obtaining 666 mg (yield: 86%) of acetyl with the organisations in the form of an oily substance.

To a solution (10 ml) videolounge acetyl compounds in chloroform add triperoxonane acid (5 ml), then stirred at room temperature for one and a half hours. The reaction solution was concentrated, neutralized with saturated aqueous sodium hydrogen carbonate solution and filtered, getting 149 mg (yield: 59%) indicated in the title compound in the form of a solid white color.

1H-NMR (CDCl3) δ: 2,48 (3H, s), 7,35 (1H, s)

MC (ESI) m/e: 143 [M+H]+.

Reference example 4

Getting 4-methylsulfonylbenzoyl

35%Aqueous hydrogen peroxide solution (18 ml) and 180 mg (0,72 mmol) of methylthiazole added to a solution (150 ml) 5.0 g (36 mmol) of 4-methylthiophenol in chloroform, and then stirred at room temperature for 30 minutes. To the reaction solution while cooling with ice add manganese dioxide, and then stirred at room temperature for 4 hours and add saturated aqueous solution of sodium chloride, then extracted with chloroform. The organic layer was washed with saturated aqueous sodium chloride, dried and concentrated, gaining 5.0 g (yield: 81%) of 4-methylsulfonylbenzoyl in a solid white color.

1,4-Diazabicyclo[2,2,2]octane (6.5 g; 58 mmol) and 5.4 g (44 mmol) of dimethylthiocarbamate to ablaut to a solution (100 ml) 5.0 g (29 mmol) of the obtained 4-methylsulfonylbenzoyl in N,N-dimethylformamide, then stirred at a temperature of 75°C for 4 hours. To the reaction solution was added water, and then extracted with ethyl acetate. The organic layer is washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. Obtained after drying and concentrating, the residue is recrystallized from a mixture solvent consisting of hexane and chloroform, receiving 4.8 g (yield: 63%) O-4-methylsulfonylmethane in a solid white color.

The obtained O-4-methylsulfonylmethane (4.8 g; 18 mmol) is stirred for 10 hours at a temperature of 180°and, after returning to room temperature, add 10 ml of methanol. To the reaction solution was added 10 ml of 2n. an aqueous solution of sodium hydroxide, and then refluxed for 8 hours and 30 minutes. To the reaction solution was added 1N. an aqueous solution of hydrogen chloride, then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried and concentrated and the resulting residue is purified column chromatography on silica gel (hexane:ethyl acetate=2:1; chloroform:methanol=10:1)to give 3.6 g (yield: 100%) specified in the connection header in the form of a solid white color.

1H-NMR (CDCl3δ : totaling 3.04 (3H, s), 3,69 (1H, s), 7,63 (2H, d, J=7,6 Hz), 7,87 (2H, d, J=7,6 Hz)

Reference example 5

Getting 4-dimethylcarbamoyl

To a solution (50 ml) of 1.30 g (5,14 mmol) 4-methylthiazole acid in tetrahydrofuran successively added 1.50 g (6,77 mmol) carbonyldiimidazole and 4,70 ml (8,35 mmol) of a solution of dimethylamine in tetrahydrofuran, and then stirred at room temperature for two and a half hours. To the reaction solution was added ethyl acetate, then washed with 1N. aqueous solution of hydrogen chloride and saturated aqueous sodium chloride. The organic layer is dried and concentrated, obtaining 960 mg of the crude amide compound as an oily substance.

To a solution (50 ml) videolounge amide compounds in chloroform is added slowly 980 mg (4,90 mmol) 3-chlormadinone acid, and then stirred for 1 hour. To the reaction solution was added saturated aqueous sodium hydrogen carbonate solution, and then stirred for 30 minutes and extracted with ethyl acetate. The organic layer is washed with water and saturated aqueous sodium chloride, dried and concentrated, obtaining 910 mg of the crude sulfoxide connection in the form of an oily substance.

To a solution (20 ml) videolounge sulfoxide connection consistently dobavlaut and 1.56 ml (to 13.4 mmol) of 2,6-lutidine and 1.80 ml (12.9 mmol) of anhydride triperoxonane acid, then stirred at room temperature for 1 hour. The reaction solution is concentrated and to the residue add 5 ml of triethylamine and 5 ml of methanol, and then stirred for 30 minutes. The reaction solution is concentrated and to the residue is added diethyl ether, and then washed with 1N. an aqueous solution of hydrogen chloride and a saturated aqueous solution of sodium bicarbonate. The organic layer is dried and concentrated, getting 487 mg (yield: 62%) indicated in the title compound as orange oily compounds. The resulting crude product is used in the next reaction without purification.

1H-NMR (CDCl3) δ: 3,03 (3H, c), 3,14 (3H, c), 7,22-7,38 (3H, m), 7,46-7,52 (1H, m)

MS (ESI) m/e: 182 [M+H]+.

Reference example 6

Getting 4-dimethylaminoacetonitrile

Hydrochloride dimethylaminoethoxide (2,40 g; 17,1 mmol) and of 5.83 g (42,2 mmol) of potassium carbonate successively added to a solution (70 ml) 3.00 g (to 13.6 mmol) of 4-itfeel in N,N-dimethylformamide, and then stirred at a temperature of 70°C for 15 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated aqueous sodium chloride, dried and kontsentrirovannyi the residue purified speakers chromatog what afia on silica gel (chloroform:methanol=30:1), getting 840 mg (yield: 21%) improsoned in the form of an oily substance.

Ethylene glycol (120 μl; of 2.15 mmol), 305 mg (2.21 mmol) of potassium carbonate, 150 μl (1,08 mmol) 4-methoxytoluene and 20 mg (0,105 mmol) of copper iodide are added to a solution (8 ml) 317 mg (1,08 mmol) videolounge improsoned in 2-propanol and the reaction solution is refluxed for 40 hours. The reaction solution is filtered through celite and the filtrate partitioned between chloroform and saturated aqueous sodium chloride. The organic layer is dried and concentrated in vacuo, getting 298 mg of an oily substance. To the oily substance successively added 180 μl of anisole and 1.5 ml three-forexpros acid, and then stirred at a temperature of 70°C for 2 hours. The reaction solution is concentrated and the crude product is used for the next reaction without purification.

MS (ESI) m/e: 198 [M+H]+.

Industrial applicability

A new derivative of 2-pyridinecarboxamide according to the present invention corresponding to the formula (I), shows excellent activity against glucokinase and, therefore, it can be used in medicine for the treatment and/or prevention of diabetes, complications caused by diabetes, or obesity.

1. The compound of formula (I):

[where

-X1-R1is phenylsulfanyl group, 4-hydroxyethylaminophenol group, 4-methylphenylsulfonyl group, 4-methoxyphenylalanine group, 4-ethoxytrimethylsilane group, 4-methylcarbamoylmethyl group, 4-dimethylcarbamodithioato group, 4-cyanophenylacetic group, 4-triftormetilfullerenov group, 4-fortunaltely group, 2-fortunaltely group, 4-methylcarbamoylmethyl group, 4-methylsulfinylphenyl group, 4-dimethylaminoethylacrylate group, pyridine-4-ylsulphonyl group, pyridine-3-ylsulphonyl group, 6-methoxypyridine-4-ylsulphonyl group, 6-methoxypyridine-3-ylsulphonyl group and 6-methylpyridin-3-ylsulphonyl group;

D is O or S;

R2and R3each means a hydrogen atom;

formula (II):

means triazolyl group, imidazolidinyl group, thiazolino group and pyridyloxy group which may have in cycle 1 or 2 groups selected from the group consisting of lower alkyl groups, lower alkoxygroup, triptorelin group, a hydroxy-group, hydroxyalkyl group (the hydrogen atom hydroxycut hydroxyalkyl g is uppy, next may be substituted by a lower alkyl group and halogen atom;

formula (III):

means thiazolidine group, thiadiazolyl group, isoxazolyl group, personilnya group, peridocially group or pyridyloxy group, the cycle may have 1 or 2 substituent selected from the group consisting of lower alkyl groups, lower alkoxygroup, halogen atom, triptorelin group, hydroxyalkyl group (the hydrogen atom hydroxycut hydroxyalkyl group may further be substituted by a lower alkyl group), aminoalkyl group (the amino group may be substituted by a lower alkyl group), alkanoyloxy group, carboxyl group, alkoxycarbonyl group and ceanography]

or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where D means S.

3. The compound according to claim 1 or 2, where the cycle As represented by the following formula:

,,,,,

,,,,,

, ,,or

4. The compound according to claim 1 or 2, where the cycle means thiazolidine group, thiadiazolyl group, peridocially group, isoxazolyl group.

5. The compound according to claim 1 or 2, where the substituent in the cycle means a hydrogen atom, a C1-6alkyl group, halogen atom, hydroxys1-6alkyl group, amino1-6alkyl group or a C2-7alkanoyloxy group.

6. The compound according to claim 1, which is 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

7. The compound according to claim 1, which is 3-(4-perpenicular)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

8. The compound according to claim 1, which is 3-(4-methoxybenzenesulfonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methoxymethanol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

9. The compound according to claim 1, which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

10. The compound according to claim 1, which is 3-(4-dimethylaminoethylacrylate the Nile)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

11. The compound according to claim 1, which is 3-(4-hydroxyethylaminomethyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(thiazol-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

12. The compound according to claim 1, which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(4-methylthiazole-2-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

13. The compound according to claim 1, which is 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

14. The compound according to claim 1, which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

15. The compound according to claim 1, which is 3-(4-dimethylaminoethylacrylate)-6-(5-methyl-4H-[1,2,4]-triazole-3-ylsulphonyl)-N-([1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

16. The compound according to claim 1, which is 3-(4-dimethylaminoethylacrylate)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

17. The compound according to claim 1, which is 3-[4-(2-hydroxyethylaminomethyl)]-6-(5-methyl-4H-[1,2,]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

18. The compound according to claim 1, which is 3-(6-methylpyridin-3-ylsulphonyl)-6-(4H-[1,2,4]triazole-3-ylsulphonyl)-N-(3-methyl[1,2,4]thiadiazole-5-yl)-2-pyridinecarboxamide or its pharmaceutically acceptable salt.

19. Pharmaceutical composition that activates glucokinase comprising an effective amount of a compound according to any one of claims 1 to 18 and a pharmaceutically acceptable carrier.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula II as neuropeptide FF receptor antagonist, their pharmaceutically acceptable acid-additive salts, medication based on them, as well as their application. Compounds can be applied for treatment and prevention of diseases mediated by activity of neuropeptide FF receptor, such as pain, hyperalgesia, enuresis, for elimination of syndromes arising in case of alcohol, psychotropic and nicotine addiction, for regulation of insulin release, digestion, memory functions, blood pressure or electrolytic and energy exchange. In general formula II , A together with thiazole ring forms 4,5,6,7-tetrahydrobenzothiazole, 5,6,7,8-tetrahydro-4H-cycloheptathiazole, 5,6-dihydro-4H-cyclopentathiazole fragments; R1 represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tret-butyl, 1,1-dimethylpropyl or phenyl; R2-R6 each represents hydrogen or methyl.

EFFECT: obtaining solutions, which ca be used for treatment and prevention of diseases, mediated by activity of neuropeptide FF receptor.

6 cl, 4 tbl, 106 ex

FIELD: chemistry.

SUBSTANCE: invention was targeted at obtaining crystals of acetonitrile solvate of 6-fluor-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (compound B), which is an intermediate compound in obtaining crystals of 6-fluor-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid of III type (compound A). Compound B crystals are mostly precipitated by regulation of super-saturation during crystallisation involving acetonitrile as a solvent. Then compound A crystals of III type are obtained crystal desolvation.

EFFECT: increased efficiency of compounds.

6 cl, 4 dwg, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention refers to cyclic sulphonamide derivatives of general formula I where bonds indicated with wavy lines represent mutually cis- in relation to cyclohexane ring; R3 represents H or hydrocarbon group having up to 10 carbon atoms; Ar1 and Ar2 independently represent phenyl which carries 0-3 substitutes independently selected from halogen, CF3, CHF2; or its pharmaceutically acceptable salt. Besides, invention refers to technology of compounds of general formula I and to pharmaceutical composition based on compounds of general formula I and applied as gamma-secretase inhibitor.

EFFECT: new derivatives of cyclic sulphonamide, activating gamma-secretase inhibition and suitable for treatment and prevention of Alzheimer's disease.

9 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the general formula (I): wherein R1 is chosen from group consisting of hydrogen atom (H), -(CH2)3-, -(CH2)4-, -CH2-S-CH2-, -S-CH2-CH2-; R2 is chosen from group consisting of nitrogen (N), sulfur (S) atom; n = 0 or 1; Z is chosen from group consisting of (C2-C10)-alkyl; R3 is chosen from group consisting of H; m = 0-2; R4 is chosen from group consisting of oxygen atom (O), -CH2-; R5 is chosen from group consisting of the following groups:

wherein R6 is chosen from group consisting of H, alkyl-(C1-C5)-alkoxyl; W is chosen from group consisting of -NH wherein each "alkyl" can be linear or branched and can be also cyclic or linear, or branched and comprises such cyclic residues, and each "aryl" comprises monocyclic aromatic group comprising 5-12 carbon atoms bound with one or some heteroatoms chosen from N, O or S atoms, and to their salts and solvates. Also, invention relates to a pharmaceutical composition, to a method for their synthesis and using compounds by claims 1-6. Invention provides synthesis of novel active compounds and pharmaceutical compositions based on thereof that possess affinity to serotonin receptors of subtype 5-HT1A.

EFFECT: valuable medicinal properties of compounds, improved method of synthesis.

10 cl, 4 tbl, 26 ex

FIELD: pharmaceutical industry.

SUBSTANCE: invention proposes use of 2-amino-7-bromo-4-acetylazo[5,4-b]indol depicted by formula: against hyperbaric and hematic hypoxia and protection of liver against carbon tetrachloride poisoning. Use of this compound reduces concentration of AlAT by a factor of 2.6 and that of AcAT by a factor of 1.67.

EFFECT: increased therapeutic activity.

3 tbl

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of the formula (I): and their salts, to methods for their preparing, compositions containing thereof and their using in medicine, in particular, for prophylaxis or treatment of clinical state wherein a selective agonist of β2-adrenoceptors is prescribed.

EFFECT: valuable medicinal properties of compound and compositions.

32 cl, 4 dwg, 82 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to new compounds of formula I , or stereoisomers, or pharmaceutically acceptable salts thereof, wherein Q is SO2; n = 2 or 3; each R1 and R2 is independently H, halogen, OR22 or C1-C6-alkyl; each R3 and R4 is H; each R5 and R6 is independently H or C1-C6-alkyl optionally substituted with phenyl or R5 and R6 together with together with atom to which they are attached may form 5-7-membered ring optionally containing N as the second heteroatom optionally substituted with COOH or C1-C6-alkyl; R7 is H; R7 is optionally substituted 8013-membered bicyclic or tricyclic ring system, containing N in bridge bond and optionally 1, 2 additional heteroatoms selected from N, S wherein substituent represent 1 or 2 halogen atoms; R22 is H or C1-C6-phenyl optionally substituted with C1-C6-alkyl. Compounds of present invention specifically bond to 5-HT6 receptor and are useful in pharmaceutical compositions.

EFFECT: compounds with specific bonding to 5-HT6 receptor.

10 cl, 3 tbl, 45 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I and pharmaceutically acceptable salt thereof, wherein R1, R3, R4, R5, and R10 are independently H, halogen, C1-C4-alkyl, etc.; R2 is H, halogen, NO2, etc.; R6 is H, C1-C6-alkyl, C1-C6-alkoxy-substituted C1-C4-alkyl, etc.; R7 is H, C1-C4-alkyl or C2-C4-alkenyl, optionally substituted with halogen; R8 and R9 are H, R11 and R12; meanings of the rest substituents are as define in specification.

EFFECT: new compounds with value biological properties and useful as drug having activity in relates to progesterone receptor.

15 cl, 3 tbl, 80 ex

FIELD: chemistry.

SUBSTANCE: new compounds with formula Ia are proposed, where: P represents pyridine or pyrimidine; R1 represents hydrogen; R2 is chosen from halogen, nitro, C0-6alkylheteroaryl, (CO)OR4, trifluoromethyl, C0-6alkylcyano, C0-6alkylNR4R5, OC1-6alkylNR4R5, C0-6alkylCONR4R5, C0-6alkyl(SO2)NR4R5 and X1R6 group, where X1 represents a direct link; R6 represents a 5- or 6-member heterocyclic group, containing one or two heteroatoms, independently chosen from N, O, and S, for which the given heterocyclic group can be unsaturated and can be substituted with by one substitute, chosen from W; m equals 0, 1, or 2; R3 is chosen from CO(OR4), C0-6alkylNR4R5, C0.6alkylCONR4R5, OC1-6alkylNR4R5 C1-6alkyl(SO2)NR4R5; n equals 1 or 2; R4 is chosen from hydrogen, C1-6alkyl; R5 is chosen from hydrogen, C1-6 alkyl, C0-6 alkyl C3-6 cycloalkyl, C0-6 alkylaryl, C0-6alkylheteroaryl and C1-6alkylNR14R15 or R4 and R5 together can form a 4-, 5-, 6- or 7-member heterocyclic group, containing one or more heteroatoms, independently chosen from N and O, where the given heterocyclic group can be substituted by group Y; and where any C1-6alkyl, indicated in defining R2-R5, can be substituted with one or more one Z group; R14 and R15 together can form a 5-member heterocyclic group, containing one or more heteroatoms, independently chosen from N and O; W and Z are independently chosen from halogen, CN, OR16, C1-6alkyl, trifluoromethyl, trifluoromethoxy, 5-member heterocyclic group, containing one heteroatom, independently chosen from N, for which the given heterocyclic group can be substituted with group Y; Y is chosen from oxo, halogen, C1-6alkyl, C0-6alkylaryl, NR16R17, phenyl, C0-6alkylaryl, where the phenyl and C0-6alkylaryl groups can be substituted with nitro, trifluoromethyl; R16 and R17 are independently chosen from hydrogen and C1-6alkyl, or where R16 and R17 together can form a 5-member heterocyclic group, containing one heteroatom, chosen from N; in form of a free base or pharmaceutical salt. Formula Ia compounds have inhibiting effect to glycogen-synthase-kinase-3 (GSK3). The invention also relates to the method of obtaining the proposed compounds and to new intermediate compounds, used in them, pharmaceutical compositions, containing the given therapeutically active compounds, and use of the given active compounds in therapy for treating conditions, related to GSK3.

EFFECT: new method of obtaining indole derivatives.

33 cl, 1 tbl, 112 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method for obtaining 5-{2-[5-{2-[1,3,5-ditiazinan-5-il]ethyl}-4-methyl-1,3,5-tiadiazinan-3-il]ethyl} 1,3,5-ditiazinan with formula including interaction of methyltriethyltetaraamin with water solution of formaldehide saturated with hydrogen sulphide. The given compound can find application as selective sorbents and extragents of precious metals and special reagents for inhibition of vital functions of bacteria in various technological media.

EFFECT: efficient method for obtaining 5-{2-[5-{2-[1,3,5-ditiazinan-5-il]ethyl}-4-methyl-1,3,5-tiadiazinan-3-il]ethyl} 1,3,5-ditiazinan.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. The compounds claimed by the invention have inhibition effect on VR1 receptor activation and can be applied in pain prevention or treatment. In the general formula (I) , or , L is a low alkylene, E cycle is benzene or 5-membered heteroaromatic ring containing sulfur atom as a heteroatom, D cycle is a monocyclic or bicyclic hydrocarbon cycle optionally condensed with C5-7 cycloalkyl, 6-membered monocyclic heteroaromatic cycle containing nitrogen atom as heteroatom or 9-11-membered bicyclic heteroaromatic cycle containing 1 to 3 equal or different heteroatoms selected out of the group including N, S and O, G cycle is a 5-7-membered monocyclic saturated or partially saturated heterocycle or 10-membered bicyclic heterocycle containing 1 to 3 equal or different heteroatoms selected out of the group including N, S and O. The invention also concerns pharmaceutical composition based on the said compounds, and application thereof in obtaining pain prevention or treatment medication, and a method of pain prevention or treatment.

EFFECT: obtaining prevention or treatment medium against pain.

24 cl, 470 ex, 41 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to the new compounds presented by the following formula (I), or to the pharmaceutically acceptable salts: , where R1 and R2 represent substitutes, adjoining with each other and with two carbonic atoms, to each of which they are adjoined forming the group presented by the following formula: 1) , or

2) , , , , , , , , or

3) or

4) , , or

where hydrogen atom in each cyclic group can be substituted bi 1-4 substitutes selected fro the following group of substitutes B1, R3 represents hydrogen atom or methyl group; and R6 represents substitute selected from the following group of A1 substitutes, the group of A1 substitutes: (1) hydrogen atom, (2) C1-C6 alkoxy group; substitute B1 group: (1) hydrogen atom, (2) hydroxyl group, (3) oxo group, (4) C1-C6 alkanoyl group, (5) C3-C8 cycloalkyl group, (6) C1-C6 alkyl group (where C1-C6 alkyl group can be substituted by C1-C6 alkoxy group), (7) C1-C6 alkoxy group, (8) C1-C6 alkoxyimino group, (9) C5-C6 cycloalkyl group, derived by two C1-C3 alkyl groups joined to the same carbonic atom with hydrogen atom and the carbons. The invention is also relates to the pharmaceutical composition.

EFFECT: production of the new biologically active compounds and pharmaceutical compositions on their basis having inhibitor potency towards to serotonine1A receptor.

34 cl, 73 ex, 12 tbl, 4 dwg

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to compounds with formula (I), their pharmaceutical salts or N-oxide used as an inhibitor to replication and/or proliferation of HCV, to the method of inhibiting replication or proliferation of hepatitis C virion using formula (I) compounds, as well as to pharmaceutical compositions based on them. The compounds can be used for treating or preventing infections, caused by hepatitis C virus. In general formula (I) cycle B is an aromatic or non-aromatic ring, which contains two heteroatoms, where X and Y, each is independently chosen from C, CH, N or O, under the condition that, both X and Y are not O and that, both X and Y are not N; U and T represent C; Z represents -CH-; A represents N or -CR2-; B represents -CR3-; D represents N or -CR4-; E represents N or -CR5-; G represents N or -CR6-; J represents N or -CR14-; K represents -CR8-; L represents N or -CR9-; M represents N or -CR10-; R2 and R6, each is independently chosen from a group, consisting of hydrogen, halogen, C1-C6alkyl, substituted C1-C6alkyl, C1-C6alkoxy, C1-C6substituted alkoxy, C1-C6alkoxycarbonyl, cycloheteroalkyl, substituted cycloheteroalkyl, -O-carbamoil, substituted -O-carbamoil, halogen C1-C6alkyl, diC1-C6alkylamino, substituted diC1-C6alkylamino and sylye ethers, where cycloheteroalkyl is a 3-7-member ring, containing 1-2 heteroatoms, chosen from N and O, under the condition that, one of R2 and R6 is not hydrogen; R3 and R5, each is independently chosen from a group, consisting of hydrogen, halogen; R4 represents hydrogen; R7 represents - NR11C(O)R12; R8, R9, R10 and R14, each is independently represents hydrogen; R11 represents hydrogen, C1-C6alkyl; and R12 is chosen from a group, consisting of halogen C1-C6alkyl; where each substituted group is substituted with one or more groups, chosen from -Q, -R40, -OR40, -C(O)R40, -C(O)OR40, where each Q independently represents halogen, R40 and R41 are independently chosen from a group consisting of hydrogen, C1-C6alkyl, C1-C6alkoxy, under the condition that: (i) at least one of A, D, E, G, J, L or M represents N; (ii) not more than one of A, D, E or G represents N; and (iii) not more than one of J, L or M represents N.

EFFECT: obtaining pyridyl-substituted heterocycles for treating and preventing infections, caused by hepatitis C virus.

33 cl, 85 dwg, 101 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the bonds of the formula (I) and their pharmaceutically acceptable salts in the capacity of modulators of receptors CB1 and to the pharmacological composition on their basis. Bonds can be used for treatment and prophylaxis of diseases, which are associated with the modulation of receptor CB1, for example, obesity and diabetes of type II. In the general formula (I) R1 means hydrogen or the lowest alkyl; R2 means hydrogen, the lowest alkyl, the lowest alkenyl, the lowest alkoxy-lowest alkyl, the lowest alkoxycarbonilamino-group or - (CH2)m-R2a; or R1 and R2 form together with atom of nitrogen to which they are attached, a 5-or 6-member saturated heterocyclic ring; R2a means cycloalkyl, which is not necessarily mono- or tetra-substituted independently by hydroxy-group, the lowest alkyl; C3-6cycloalkenyl, 5- or 6-member monovalent saturated heterocyclic ring, which contains from one to two heteroatoms, independently selected from nitrogen and oxygen; 5- or 6-member monovalent heteroaromatic ring, which contains from one to two heteroatoms, independently selected from nitrogen and oxygen, here note that the said heteroaromatic ring is not necessarily mono-substituted independently with the lowest alkyl; or phenyl which is not necessarily mono- or di-substituted independently with the lowest of the alkoxy group, halogen, halogenated lowest alkyl, halogenated lowest alkoxy group or nitro-group; R3 means the lowest alkyl, the lowest alkoxy-lowest alkyl, diphenyl-lowest alkyl or - (CH2)n-R3a; R3a means C3-6cycloalkyl which can be not necessarily condensed with the phenol ring; or C3-6cycloalkyl, which can be not necessarily mono-, di- or trisubstituted independently hydroxy-group, the lowest alkyl, C3-6cycloalkenyl, 5- or 6-member monovalent saturated heterocyclic ring, which contains from one to two heteroatoms, independently selected from nitrogen and oxygen, here note that the said heterocyclic rings are not necessarily mono-substituted independently by the lowest alkyl, 5- or 6-member monovalent heteroaromatic ring containing one heteroatom, independently selected from oxygen and sulfur, the aforesaid heteroaromatic ring being not necessarily mono-substituted independently with the lowest alkyl, or the phenyl, which can be not necessarily mono-, di- or trisubstituted independently by the hydroxy-group, lowest alkyl, lowest alkoxy-group, halogen, halogenated lowest alkyl, halogenated lowest alkoxy-group or nitro-group; R4 means the lowest alkyl the lowest alkoxycarbonyl; C3-6 cycloalkyl, 5- or 6-member monovalent heteroaromatic ring, which contains one or two heteroatoms, independently selected from nitrogen, the said heteroaromatic ring being not necessarily mono-substituted independently with the lowest alkyl, lowest alkoxy-group; phenoxy-lowest alkyl, in which the phenyl part is not necessarily mono-, di- or trisubstituted independently by the lowest alkoxy-group; or the phenyl, which not necessarily can be mono-, di- or trisubstituted independently, by the lowest alkyl, by the lowest alkoxy-group, by halogen, halogenated lowest alkyl, halogenated lowest alkoxy-group or nitro-group; or two adjusted substitutes of the said phenyl remainder indicate together -O-(CH2)p-O- or -(CH2)2-O-; R5 and R6 each indicates a substitute independently selected from hydrogen of lowest alkyl; R7 indicates hydrogen; m indicates 0,1 or 2; n indicates 1.

EFFECT: new bonds possess useful biological properties.

28 cl, 4 dwg, 380 ex

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

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: new compounds with formula Ia are proposed, where: P represents pyridine or pyrimidine; R1 represents hydrogen; R2 is chosen from halogen, nitro, C0-6alkylheteroaryl, (CO)OR4, trifluoromethyl, C0-6alkylcyano, C0-6alkylNR4R5, OC1-6alkylNR4R5, C0-6alkylCONR4R5, C0-6alkyl(SO2)NR4R5 and X1R6 group, where X1 represents a direct link; R6 represents a 5- or 6-member heterocyclic group, containing one or two heteroatoms, independently chosen from N, O, and S, for which the given heterocyclic group can be unsaturated and can be substituted with by one substitute, chosen from W; m equals 0, 1, or 2; R3 is chosen from CO(OR4), C0-6alkylNR4R5, C0.6alkylCONR4R5, OC1-6alkylNR4R5 C1-6alkyl(SO2)NR4R5; n equals 1 or 2; R4 is chosen from hydrogen, C1-6alkyl; R5 is chosen from hydrogen, C1-6 alkyl, C0-6 alkyl C3-6 cycloalkyl, C0-6 alkylaryl, C0-6alkylheteroaryl and C1-6alkylNR14R15 or R4 and R5 together can form a 4-, 5-, 6- or 7-member heterocyclic group, containing one or more heteroatoms, independently chosen from N and O, where the given heterocyclic group can be substituted by group Y; and where any C1-6alkyl, indicated in defining R2-R5, can be substituted with one or more one Z group; R14 and R15 together can form a 5-member heterocyclic group, containing one or more heteroatoms, independently chosen from N and O; W and Z are independently chosen from halogen, CN, OR16, C1-6alkyl, trifluoromethyl, trifluoromethoxy, 5-member heterocyclic group, containing one heteroatom, independently chosen from N, for which the given heterocyclic group can be substituted with group Y; Y is chosen from oxo, halogen, C1-6alkyl, C0-6alkylaryl, NR16R17, phenyl, C0-6alkylaryl, where the phenyl and C0-6alkylaryl groups can be substituted with nitro, trifluoromethyl; R16 and R17 are independently chosen from hydrogen and C1-6alkyl, or where R16 and R17 together can form a 5-member heterocyclic group, containing one heteroatom, chosen from N; in form of a free base or pharmaceutical salt. Formula Ia compounds have inhibiting effect to glycogen-synthase-kinase-3 (GSK3). The invention also relates to the method of obtaining the proposed compounds and to new intermediate compounds, used in them, pharmaceutical compositions, containing the given therapeutically active compounds, and use of the given active compounds in therapy for treating conditions, related to GSK3.

EFFECT: new method of obtaining indole derivatives.

33 cl, 1 tbl, 112 ex

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