Imidazopyridin-2-one derivatives, having mtor inhibiting activity

FIELD: chemistry.

SUBSTANCE: present invention relates to novel imidazopyridin-2-one derivatives of general formula or pharmacologically acceptable salts thereof, where (R1)n-A is a 1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group or 3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, B is a 3-6-member saturated or partially saturated monocyclic hydrocarbon group and can contain 1 or 2 oxygen atoms, a nitrogen atom and/or sulphonyl groups as ring components, B can have as substitutes identical or different R2 in amount of m, R2 is a substitute represented at a carbon atom or a nitrogen atom forming B, R2 is a substitute selected from a group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4alkyl group (where the C1-4 alkyl group can be substituted with 1 C1-4 alkoxy group) and a C1-4 alkoxy group, when R2 is a substitute represented at a carbon atom forming B, and R2 is a substitute selected from a group consisting of a C1-4 alkyl group and a C1-4 alkylcarbonyl group, when R2 is a substitute represented at a nitrogen atom forming B, m is any integer from 0 to 2, Q is a bond or a C1-4 alkylene group, R3 and R4 are identical or different and each denotes a hydrogen atom or a halogen atom, and R5 and R6 are identical or different and each denotes a hydrogen atom, a halogen atom or a C1-4 alkyl group. The invention also relates to specific compounds of formula (I), pharmacologically acceptable salts of compounds of formula (I), a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel imidazopyridin-2-one derivatives, having mTOR inhibiting action, are obtained.

21 cl, 161 ex

 

The technical field

The present invention relates to a new compound or its pharmacologically acceptable salt or pharmaceutical composition containing the compound or salt as an active ingredient, having the effect of inhibiting the activity of mTOR kinase.

The level of technology

Target of rapamycin in mammals (mTOR) is a serine/trionychinae with a molecular mass of 289 kDa, referred to as the target of rapamycin, a macrolide antimicrobial agent.

mTOR (also known as FRAP, RAPT1 or RAFT1) expressed in almost all organs and tissues and is involved in the PI3K-Akt signalling system. mTOR forms complexes mTORC1 and mTORC2 with adaptorname proteins, such as raptor and rictor, respectively, and transmits extracellular signals. mTORC1 activates the translation of proteins associated with malignant tumor (such as cyclin D1, myc and HIF-1α), phosphorylase his target, such as S6K and EVR-1, in the subsequent stages of the signal path. At the same time, it is assumed that mTORC2 activates signals survival of malignant tumor cells, phosphorylase its target in subsequent stages of the signaling pathway Akt Ser473.

Clinically also observed increased mTOR signaling systems in various types of malignant tumors, including malignant kidney tumor, osteosarcoma, a malignant lung tumor, malignant SDA is the role of ovarian malignant tumor of the prostate, cancer of the breast, malignant colon tumor and a malignant tumor of the liver.

Rapamycin, an mTOR inhibitor, intracellular binds to FKBP12 (FK-506 binding protein) and forms a complex. Then the complex of rapamycin/FKBP12 binds to mTOR; the activity of the mTOR kinase, as expected, inhibited this binding, and accordingly, also inhibited protein synthesis and cell proliferation. In addition, it was reported that rapamycin has an antitumor effect in patients with cancer. At the moment were carried out clinical trials of mTOR inhibitors, including CCI-779, a derivative of rapamycin.

As described above, it is believed that mTOR is an effective molecular target for the treatment of malignant tumors and that compounds with the effect of inhibiting the activity of mTOR kinase (hereinafter referred to sometimes as the activity of inhibiting mTOR), can be pharmacologically useful in the treatment of malignant tumors, in particular for the treatment of malignant tumors with enhanced mTOR signaling, such as malignant tumors with LKB mutations or TSC2 mutations, or malignant tumors with activated PTEN (non-patent references 1-3).

It is known that compounds such as derivatives of pyridopyrimidines and p is osvitnye of imidazopyridine, inhibit the activity of mTOR.

The list of references

Reference to patents

Reference patent 1: WO 2007/051493

Reference patent 2: WO 2008/023161

Link to patent 3: WO 2008/051493

Non-patent reference

Non-patent reference 1: Science, vol. 307, no. 18, 1098-1101, 2005

Non-patent reference 2: Nature, vol. 441, no. 25, 424-430, 2006

Non-patent reference 3: Drug Discovery Today, vol. 12, no. 3/4, 112-124, 2007

The invention

The technical problem

As a result of intensive research in respect of compounds with mTOR inhibitory activity, the authors of the present invention have found that the compound represented by formula (I) in accordance with the present invention effectively inhibits the activity of mTOR kinase with excellent effect of inhibiting cell proliferation. Thus, the inventors have accomplished the present invention.

Accordingly, the aim of the present invention to provide a compound or its pharmacologically acceptable salt with excellent mTOR inhibitory activity.

Another objective of the present invention to provide a pharmaceutical composition or an mTOR inhibitor, in particular anticancer agent containing the above-mentioned compound or its pharmacologically acceptable salt as an active ingredient.

Means of solving the problem

The con is specific, the present invention relates to:

(1) the compound represented by the following formula (I):

where in the General formula (I)

A represents an 8-10-membered partially saturated or aromatic condensed bicyclic nitrogen-containing heterocyclic group containing 1-3 nitrogen atom,

A may have as substituents the same or different R1with the number n,

R1is a Deputy selected from the group consisting of: hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by one or two identical or two different C1-4alkoxy groups, or-NR7aR7b), C1-4alkoxy group, halogen-C1-4alkyl group, -NR7aR7b, -C(O)R8and-C(O)NR9aR9b,

n is any integer from 0 to 3,

R7a, R7b, R9aand R9bare the same or different and represent each a hydrogen atom or a C1-4alkyl group (where C1-4the alkyl group may be substituted by 1 or 2 hydroxy groups),

R8represents a hydrogen atom, a hydroxy group, a C1-4alkyl group or a C1-4alkoxy group,

B represents a 3-7-membered saturated or partially of NASA the military monocyclic hydrocarbon group and may contain 1 or 2 oxygen atom, the sulfur atom, nitrogen atom, sulfinyl group and/or sulfonylurea groups as substituents of the ring

B may have as substituents the same or different R2with the number m,

R2is a Deputy, presented on the carbon atom or nitrogen atom forming B,

R2is a Deputy selected from the group consisting of: hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by 1 or 2 C1-4alkoxy groups), (C1-4alkoxy group, halogen-C1-4alkyl group, a C1-4alkylsulfonyl group, C1-4alkylcarboxylic group, and-NR10aR10bwhen R2is a Deputy, presented on the carbon atom constituting the B and R2is a Deputy selected from the group consisting of a hydroxy group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by 1 or 2 C1-4alkoxy groups), (C1-4alkoxy group, halogen-C1-4alkyl group, a C1-4alkylsulfonyl group, C1-4alkylcarboxylic group, and-NR10aR10bwhen R2is a Deputy, presented at the nitrogen atom, forms B,

R10aand R10bare the same is or are different and represent each a hydrogen atom or a C 1-4alkyl group,

m is any integer from 0 to 3,

Q is a bond or C1-4alkylenes group,

R3and R4are the same or different and represent each a hydrogen atom, a halogen atom, a C1-4alkyl group, halogen-C1-4alkyl group or cyano group, and

R5and R6are the same or different and represent each a hydrogen atom, halogen atom or C1-4alkyl group, or R5and R6together can form an oxo group, or together with the carbon atom to which R5and R6linked, can form a C3-8cycloalkyl group,

or its pharmacologically acceptable salt;

(2) the compound or its pharmacologically acceptable salt according to above described paragraph (1), where A represents a condensed bicyclic nitrogen-containing heterocyclic group containing from 1 to 3 nitrogen atoms, in which:

(a) ring that is directly connected to imidazopyridine ring that is a partially saturated or aromatic 6-membered ring containing 0 to 2 nitrogen atoms, and

(b) ring, not associated directly with imidazopyridine ring that is a partially saturated or aromatic 5-membered ring containing 1 or 2 atoms is nitrogen;

(3) the compound or its pharmacologically acceptable salt according to above described paragraph (1), where A is indolenine group, isoindolyl group, indazolinone group, pyrrolopyridine group, pyrazolopyrimidine group, imidazopyridine group, pyrrolidinyl group, pyrazolopyrimidinone group, imidazolidinyl group, pyrrolopyrimidine group, pyrazolopyrimidinone group, imidazolidinyl group, pyrrolopyrimidine group, pyrazolopyrimidine group or imidazopyridine group;

(4) the compound or its pharmacologically acceptable salt according to any of the above items (1)to(3), where R1is a Deputy, identically or otherwise selected from the group consisting of fluorine atom, chlorine atom, cyano group, methyl group, ethyl group, isopropyl group, methoxy group, ethoxy group, triptorelin group, methoxymethyl group, ethoxymethyl group, amino group, methylamino group, dimethylamino group, methylethylamine group, propylamino group, (2-hydroxyethyl)(methyl)amino group, formyl group, acetyl group, ethylcarbazole group, ethoxycarbonyl group, carboxyl group, carbamoyl group and methylcarbamoyl group, and n equal to either the elomo number from 0 to 2;

(5) the compound or its pharmacologically acceptable salt according to any of the above items (1)to(4), where R3represents a hydrogen atom, fluorine atom, chlorine atom, cyano group or methyl group and R4represents a hydrogen atom;

(6) the compound or its pharmacologically acceptable salt according to any of the above items (1)to(5), where Q is a bond or methylene group;

(7) the compound or its pharmacologically acceptable salt according to any of the above items (1)to(6), where R5and R6are the same or different and represent each a hydrogen atom, halogen atom or C1-4alkyl group;

(8) the compound or its pharmacologically acceptable salt according to any of the above items (1)to(7), where B represents a C3-7cycloalkyl group, tetrahydrofuryl group, dihydropyrazolo group, tetrahydropyranyloxy group, dioxinlike group, piperidino group, piperazinilnom group or 1,1-deoxycorticosterone group;

(9) the compound or its pharmacologically acceptable salt according to any of the above items (1)to(8), where R2represents a hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl group, a C1-4 alkoxy-C1-4alkyl group, a C1-4alkoxy group, a C1-4alkylsulfonyl group or a C1-4alkylcarboxylic group, when R2is a Deputy, presented on the carbon atom that forms B, R2represents a C1-4alkyl group, a C1-4alkylsulfonyl group or a C1-4alkylcarboxylic group, when R2is a Deputy, presented at the nitrogen atom, forms a, B, and m is any integer from 0 to 2;

(10) the compound according to above described paragraph (1), where the compound is any compound selected from:

1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it,

1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it,

6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it,

6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it,

1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it,

2,6-anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol,

2,6-anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol,

2,6-anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol,

2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol,

2,6-anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol and

2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol;

(11) 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-ONU;

(12) 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-ONU;

(13) 6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-ONU;

(14) 6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-ONU;

(15) 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-ONU;

(16) 2,6-anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol;

(17) 2,6-anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridi the-1-yl]-L-threo-hexitol;

(18) 2,6-anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol;

(19) 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol;

(20) 2,6-anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol;

(21) 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol;

(22) pharmacologically acceptable salts of the compounds according to any of the above items(10)-(21);

(23) a pharmaceutical composition containing the compound or its pharmacologically acceptable salt according to any of the above items (1)to(21) as an active ingredient;

(24) the antitumor agent containing the compound or its pharmacologically acceptable salt according to any of the above items (1)to(21) as an active ingredient;

(25) the mTOR inhibitor containing the compound or its pharmacologically acceptable salt according to any of the above items (1)to(21) as an active ingredient; and

(26) the antitumor agent according to above described paragraph (24), where the tumor is leukemia is, lymphoma, multiple myeloma, brain tumor, malignant tumor of the head and neck, cancer of the esophagus, cancer of the stomach, appendicularia malignant tumor, colon tumor, a malignant tumor of the anal canal malignant tumor of the gallbladder, cancer of the bile ducts, cancer of the pancreas, stromal tumor of the gastrointestinal tract, cancer of the lung, malignant liver tumor, mesothelioma, a malignant tumor of the thyroid gland, cancer of the kidney, cancer of the prostate, neuroendocrine tumor, a melanoma, a malignant tumor of the breast, cancer of the endometrium, cancer of the cervix uterine a malignant tumor, ovarian carcinoma, osteosarcoma, soft tissue sarcoma, Kaposi's sarcoma, myosarcoma, a malignant tumor of the kidney, cancer of the bladder and/or malignant tumors of the testes.

The present invention also relates to a method for prevention, treatment or prevention of tumor recurrence, including the introduction of a warm-blooded animal (preferably a human) a compound or its pharmacologically acceptable salt according to any of the description is the R above, selected from (1)to(21)the pharmaceutical composition according to above item (23), an inhibitor of mTOR, as described in the above item (25) or antitumor agent in accordance with the above paragraphs (24) or (26).

The present invention further refers to:

(27) the compound represented by the following formula (II):

where in the General formula (II)

R1a, R1band R1care the same or different and represent each a Deputy selected from the group consisting of a hydrogen atom, hydroxy group, halogen atom, cyano group, C1-4alkyl groups (where C1-4the alkyl group may be substituted by one or two identical or different C1-4alkoxy groups, or-NR7aR7b), C1-4alkoxy group, halogen-C1-4alkyl group, -NR7aR7b, -C(O)R8and-C(O)NR9aR9b,

Z represents C-R1dor nitrogen atom,

R1drepresents a hydrogen atom, halogen atom or C1-4alkyl group,

R7a, R7b, R9aand R9bare the same or different and represent each a hydrogen atom or a C1-4alkyl group (where C1-4the alkyl group may be substituted by 1 or 2 hydroxy groups),

R8the present is the focus of a hydrogen atom, hydroxy group, a C1-4alkyl group or a C1-4alkoxy group,

B represents a 3-7-membered saturated or partially saturated monocyclic hydrocarbon group and may contain 1 or 2 oxygen atoms, sulfur atoms, nitrogen atoms, sulfinyl group and/or sulfonylurea groups as constituents of the ring

B may have as substituents the same or different R2the number of m,

R2is a Deputy, presented on the carbon atom or nitrogen atom forming B,

R2is a Deputy selected from the group consisting of hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by 1 or 2 C1-4alkoxy groups), (C1-4alkoxy group, halogen-C1-4alkyl group, a C1-4alkylsulfonyl group, C1-4alkylcarboxylic group, and-NR10aR10bwhen R2is a Deputy, presented on the carbon atom constituting the B and R2is a Deputy selected from the group consisting of a hydroxy group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by 1 or 2 C1-4alkoxy groups), (C1-4alkoxy group, halogen-C1-4alkyl group, a C14 alkylsulfonyl group, C1-4alkylcarboxylic group, and-NR10aR10bwhen R2is a Deputy, presented at the nitrogen atom, forms B,

R10aand R10bare the same or different and represent each a hydrogen atom or a C1-4alkyl group,

m is any integer from 0 to 3,

Q is a bond or C1-4alkylenes group,

R3and R4are the same or different and represent each a hydrogen atom, a halogen atom, a C1-4alkyl group, halogen-C1-4alkyl group or cyano group, and

R5and R6are the same or different and represent each a hydrogen atom, halogen atom or C1-4alkyl group, or R5and R6together can form an oxo group, or together with the carbon atom to which R5and R6linked, can form a C3-8cycloalkyl group,

or its pharmacologically acceptable salt;

(28) the compound or its pharmacologically acceptable salt according to the above item (27), where R1a, R1band R1care the same or different and represent each a hydrogen atom, a halogen atom, a C1-4alkyl group or a C1-4alkoxy group;

(29) the compound Il is its pharmacologically acceptable salt according to the above item (27) or (28), where R3represents a hydrogen atom, fluorine atom, chlorine atom, cyano group or methyl group and R4represents a hydrogen atom;

(30) the compound or its pharmacologically acceptable salt according to any of the above items (27)to(29), where Q is a bond or methylene group;

(31) the compound or its pharmacologically acceptable salt according to any of the above items (27)to(30), where R5and R6are the same or different and represent each a hydrogen atom, halogen atom or C1-4alkyl group;

(32) the compound or its pharmacologically acceptable salt according to any of the above items (27)to(31), where B represents a C3-7cycloalkyl group, tetrahydrofuryl group, dihydropyrazolo group, tetrahydropyranyloxy group, dioxinlike group, piperidino group, piperazinilnom group or 1,1-deoxycorticosterone group;

(33) the compound or its pharmacologically acceptable salt according to any of the above items (27)to(32), where R2represents a hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl group, a C1-4alkoxy-C1-4alkyl group, a C1-4alkoxy group, a C1-4alkylsulfonyl group or a C alkylcarboxylic group, when R2is a Deputy, presented on the carbon atom that forms B, R2represents a C1-4alkyl group, a C1-4alkylsulfonyl group or a C1-4alkylcarboxylic group, when R2is a Deputy, presented at the nitrogen atom, forms a, B, and m is any integer from 0 to 2;

(34) a pharmaceutical composition containing the compound or its pharmacologically acceptable salt according to any of the above items (27)to(33) as an active ingredient;

(35) the antitumor agent containing the compound or its pharmacologically acceptable salt according to any of the above items (27)to(33) as an active ingredient;

(36) the mTOR inhibitor containing the compound or its pharmacologically acceptable salt according to any of the above items (27)to(33) as an active ingredient; and

(37) the antitumor agent according to the above item (35), where the tumor is leukemia, lymphoma, multiple myeloma, brain tumor, malignant tumor of the head and neck, cancer of the esophagus, cancer of the stomach, appendicularia malignant tumor, colon tumor, malignant is the first tumor of the anal canal, malignant tumor of the gallbladder, cancer of the bile ducts, cancer of the pancreas, stromal tumor of the gastrointestinal tract, cancer of the lung, malignant liver tumor, mesothelioma, a malignant tumor of the thyroid gland, cancer of the kidney, cancer of the prostate, neuroendocrine tumor, a melanoma, a malignant tumor of the breast, cancer of the endometrium, cancer of the cervix, malignant tumor, ovarian carcinoma, osteosarcoma, soft tissue sarcoma, Kaposi's sarcoma, myosarcoma, a malignant tumor of the kidney, cancer of the bladder and/or malignant tumors of the testes.

The present invention also relates to a method for prevention, treatment or prevention of tumor recurrence, including the introduction of a warm-blooded animal (preferably a human) a compound or its pharmacologically acceptable salt according to any preceding paragraph, selected from (27)-(33), pharmaceutical compositions in accordance with the above paragraph (34), an inhibitor of mTOR, in accordance with the above paragraph (36) or antitumor agent in accordance with the above paragraphs (35) or (37).

The beneficial effects of the invention/b>

The compound or its pharmacologically acceptable salt, having the formula (I) in accordance with the present invention, has a strong inhibitory activity against mTOR and inhibits cell proliferation. In addition, in an animal model with transplanted tumor compound or salt inhibits the phosphorylation of S6 and Akt in tumor tissue and has an excellent antitumor effect. Thus, the compound or its pharmacologically acceptable salt in accordance with the present invention, or a pharmaceutical composition comprising the compound or its pharmacologically acceptable salt in accordance with the present invention as an active ingredient, used as anti-cancer agents, in particular, the means for the treatment of tumors, such as malignant disease of the circulatory system, such as leukemia, lymphoma or multiple myeloma, brain tumor, malignant tumor of the head and neck, cancer of the esophagus, cancer of the stomach, appendicularia malignant tumor, colon tumor, a malignant tumor of the anal canal malignant tumor of the gallbladder malignant tumor of the bile ducts, cancer of the pancreas, stromal tumor of Zheludok is about-intestinal tract, malignant lung tumor, a malignant liver tumor, mesothelioma, a malignant tumor of the thyroid gland, cancer of the kidney, cancer of the prostate, neuroendocrine tumor, a melanoma, a malignant tumor of the breast, cancer of the endometrium, cancer of the cervix, malignant tumor, ovarian carcinoma, osteosarcoma, soft tissue sarcoma, Kaposi's sarcoma, myosarcoma, a malignant tumor of the kidney, cancer of the bladder and/or malignant tumors of the testes. The compound, or salt or pharmaceutical composition is effective as a treatment for tumors with mutations of genes involved in signaling pathways, including mTOR, such as tumors with LKB mutations or TSC2 mutations or tumors with inactivated PTEN, including the above-mentioned tumors.

Description of embodiments

Used herein, the term "C1-4alkyl group" represents a linear or branched alkyl group having from 1 to 4 carbon atoms. Examples of the group include methyl group, ethyl group, through the group, isopropyl group, boutelou group, isobutylene group, sec-boutelou group and tert-boutelou group. "C3-8cycloalkyl group" is samoylichenko hydrocarbon group, having 3 to 8 carbon atoms, and "C3-7cycloalkyl group" represents an alicyclic hydrocarbon group having 3 to 7 carbon atoms. Examples of such groups include cyclopropyl group, cyclobutyl group, cyclopentyl group and tsiklogeksilnogo group, respectively. Examples of the "halogen atom" include fluorine atom, chlorine atom, bromine atom and iodine atom. "Halogen-C1-4alkyl group" represents a group in which the above C1-4alkyl group substituted by the same or different 1-3 above halogen atoms. Examples of groups include pharmacylow group, deformational group, triptorelin group, chloromethylene group, dichloromethylene group, trichlorethylene group, 2-foretelling group, 1,2-deperately group, 2-triptorelin group, 2-chloraniline group, 1,2-dichloroethylene group, 1,1,2-trichlorethylene group, 1,2,2-trichlorethylene group and 2,2,2-trichlorethylene group. "C1-4alkoxy group" is a group formed of the above "C1-4alkyl group and an oxygen atom. Examples of the group include methoxy group, ethoxy group, propoxy group, isopropoxy group. "C1-4acylcarnitine group" is a group formed of the above "C1-4alkyl group and a carbonyl what Ruppel. Examples of the group include acetyl group, ethylcarbitol group and propelleronline group. "C1-4alkylsulfonyl group" represents a group in which the above C1-4an alkyl group substituted, or represents sulfonyloxy group. Examples of groups include methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group and isopropylacetanilide group. "C1-4Allenova group" represents a linear or branched alkylenes group having from 1 to 4 carbon atoms. Examples of the group include methylene group, ethylene group, propylene group and metilbutilovy group.

Used herein, the term "8-10-membered partially saturated or aromatic condensed bicyclic nitrogen-containing heterocyclic group" in the definition of A is an 8-10-membered bicyclic aromatic ring containing 1 to 3 nitrogen atoms, which may be partially saturated. Two monocycle, forming a bicyclic nitrogen-containing heterocyclic group, identically or differently selected from 5-membered or 6-membered rings. Examples of such a condensed bicyclic nitrogen-containing heterocyclic groups include indolizinyl group, isoindolyl group, indolenine group, indolinyl group,indazolinone group, pyrrolopyridine group, pyrazolopyrimidine group, imidazopyridine group, pyrazolopyrimidinone group, parinello group, hyalinella group, izohinolinove group, pinolillo group and naphthalenyloxy group.

"3-7-Membered monocyclic saturated or partially saturated cyclic hydrocarbon group" in the definition of B belongs to a 3-7-membered saturated or partially saturated cyclic hydrocarbon group, which may contain the same or different 1 or 2 nitrogen atom, oxygen atom, sulfur atom, sulfoxide group and/or sulfonylurea groups as constituents of the ring. Examples of such cyclic hydrocarbon groups include C3-7cycloalkyl groups, such as cyclopropyl group, cyclobutyl group, cyclopentenone group or tsiklogeksilnogo group, pyrrolidinyl group, imidazolidinyl group, pyrazolidinone group, piperideine group, piperazinilnom group, morpholinyl group, dihydropyridine group, tetrahydrofuryl group, dihydropyridine group, tetrahydropyranyl group, dioxinlika group, tetrahydroquinoline group, 1-oxitetraciclina group and 1,1-deoxycorticosterone group.

Deputies and of the structure in the General formula (I) will be described further below.

A represents an 8-10-membered partially saturated or aromatic condensed bicyclic nitrogen-containing heterocyclic group containing from 1 to 3 nitrogen atoms. Preferably the ring is directly connected to imidazopyridine ring number two rings, forming A represents a partially saturated or aromatic 6-membered ring containing 0 to 2 nitrogen atoms, and the ring is not directly associated with imidazopyridine ring that is a partially saturated or aromatic 5-membered ring, streamie 1 or 2 nitrogen atom. A may have a nitrogen atom in the condensed plot.

More specifically, A represents indolenine group, isoindolyl group, indazolinone group, pyrrolopyridine group, pyrazolopyrimidine group, imidazopyridine group, pyrrolidinyl group, pyrazolopyrimidinone group, imidazolidinyl group, pyrrolopyrimidine group, pyrazolopyrimidinone group, imidazolidinyl group, pyrrolopyrimidine group, pyrazolopyrimidine group or imidazopyridine group, for example. A is preferably indolenine group, indazolinone group, pyrrolopyridine group, pyrazolopyrimidine group, imidazopyridine group, pyrrolopyridine the second group, pyrazolopyrimidinone group or pyrrolopyrimidine group. A preferably represents 1H-indol-5-ilen group, 1H-indol-2-ilen group, 1H-indazol-5-ilen group, 1H-pyrrolo[2,3-b]pyridine-5-ilen group, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 1H-pyrrolo[3,2-b]pyridine-5-ilen group, 1H-pyrrolo[3,2-b]pyridine-6-ilen group, 1H-pyrrolo[2,3-c]pyridine-5-ilen group, 1H-pyrazolo[3,4-b]pyridine-5-ilen group, 3H-imidazo[4,5-b]pyridine-6-ilen group, 7H-pyrrolo[2,3-c]pyridazin-3-ilen group, a pyrazolo[1,5-a]pyrimidine-6-ilen group or 5H-pyrrolo[2,3-b]pyrazin-2-ilen group. A is particularly preferably 1H-indol-5-ilen group or 1H-pyrrolo[2,3-b]pyridine-5-ilen group.

In the General formula (I) -(R1)n shows that A is substituted by the same or different R1the number n. A preferably substituted R1on the carbon atom, forming A.

R1is a Deputy selected from the group consisting of: hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by one or two identical or different C1-4alkoxy groups, or-NR7aR7b), C1-4alkoxy group, halogen-C1-4alkyl group, -NR7aR7b, -C(O)R8and-C(O)NR9aR9b.

R7a, R7b, R and R9bare the same or different and represent each a hydrogen atom or a C1-4alkyl group (where C1-4the alkyl group may be substituted by 1 or 2 hydroxy groups). Preferably R7a, R7b, R9aand R9bare the same or different and represent each a hydrogen atom, methyl group, ethyl group, hydroxymethylene group or hydroxyethylene group. More preferably R7a, R7b, R9aand R9bare the same or different and represent each a hydrogen atom, methyl group or hydroxyethylene group.

R8represents a hydrogen atom, a hydroxy group, a C1-4alkyl group or a C1-4alkoxy group, preferably a hydrogen atom, a hydroxy group or a C1-4alkoxy group, and more preferably a hydroxy group, methoxy group or ethoxy group.

R1represents preferably Deputy, identically or otherwise selected from the group consisting of fluorine atom, chlorine atom, cyano group, methyl group, ethyl group, isopropyl group, methoxy group, ethoxy group, triptorelin group, methoxymethyl group, ethoxymethyl group, amino group, methylamino group, dimethylamino group, methylethylamine group, Propylamine the group, (2-hydroxyethyl)(methyl)amino group, formyl group, acetyl group, ethylcarbazole group, ethoxycarbonyl group, carboxyl group, carbamoyl group and methylcarbamoyl group. R1represents preferably Deputy, identically or otherwise selected from the group consisting of fluorine atom, chlorine atom and a methyl group.

n is any integer from 0 to 3, more preferably any integer from 0 to 2.

Part of the structure represented by the following formula (III):

represents preferably 1H-indol-5-ilen group, 4-fluoro-1H-indol-5-ilen group, 6-fluoro-1H-indol-5-ilen group, 7-fluoro-1H-indol-5-ilen group, 7-fluoro-3-methyl-1H-indol-5-ilen group, 7-fluoro-4-methyl-1H-indol-5-ilen group, 3,4-dimethyl-7-fluoro-1H-indol-5-ilen group, 1H-indazol-5-ilen group, 1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 6-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 6-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 6-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-ilnu the group, 3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-methoxy-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-amino-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-amino-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 1H-pyrrolo[3,2-b]pyridine-5-ilen group, a pyrazolo[1,5-a]pyrimidine-6-ilen group, 1H-pyrazolo[3,4-b]pyridine-5-ilen group, 5H-pyrrolo[2,3-b]pyrazin-2-ilen group, 7H-pyrrolo[2,3-c]pyridazin-3-ilen group or 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-ilen group.

Part of the structure is preferably a 1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group or 3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group.

B represents a 3-7-membered monocyclic saturated or partially saturated cyclic hydrocarbon group, and as constituting the ring may contain 1 or 2 oxygen atom, sulfur atom, atom azo is a, sulfinyl group and/or sulfonylurea group. B also includes stereoisomeric structure, if such patterns exist.

More specifically, B is, for example, C3-7cycloalkyl group, follow group, pyranyloxy group, dioxinlike group, piperidino group, piperazinilnom group, tipirneni group, 1-oxidational group or 1,1-dioxythiophene group. B preferably represents C3-7cycloalkyl group, tetrahydrofuryl group, dihydropyrazolo group, tetrahydropyranyloxy group, dioxinlike group, piperidino group, piperazinilnom group or 1,1-deoxycorticosterone group. B is preferably cyclopropyl group, tsiklogeksilnogo group, tetrahydrofuran-3-ilen group, 3,6-dihydro-2H-Piran-4-ilen group, 5,6-dihydro-2H-Piran-3-ilen group, tetrahydro-2H-Piran-2-ilen group, tetrahydro-2H-Piran-3-ilen group, tetrahydro-2H-Piran-4-ilen group, piperidine-4-ilen group, piperazine-1-ilen group, morpholine-3-ilen group, morpholine-4-strong group, 1,1-dissidocerida-2H-thiopyran-4-ilen group or 1,4-dioxane-2-ilen group. B is particularly preferably tsiklogeksilnogo group, tetrahydro-2H-Piran-2-ilen group, tetrahydro-2H-Piran-3-ilen group, tetrahed the on-2H-Piran-4-ilen group, 5,6-dihydro-2H-Piran-3-ilen group or 1,4-dioxane-2-ilen group.

In the General formula (I) -(R2)m shows that B is substituted by the same or different R2the number m. The structure in which B is substituted by R2also includes stereoisomeric structure, if such patterns exist.

R2is a Deputy, presented on the carbon atom or nitrogen atom forming B. When B is substituted by R2on the carbon atom, B can be substituted by the same or different two R2on the carbon atom.

R2is a Deputy selected from the group consisting of hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by 1 or 2 C1-4alkoxy groups), (C1-4alkoxy group, halogen-C1-4alkyl group, a C1-4alkylsulfonyl group, C1-4alkylcarboxylic group, and-NR10aR10bwhen R2is a Deputy, presented on the carbon atom constituting B. R10aand R10bare the same or different and represent each a hydrogen atom or a C1-4alkyl group. Preferably R10aand R10bare the same or different and represent each a hydrogen atom, methyl group or ethyl group is at. More preferably R10aand R10bare both hydrogen atoms.

R2when he is Deputy to the carbon atom forming B, is preferably a hydroxy group, halogen atom, cyano group, oxo group, a C1-4alkyl group, a C1-4alkoxy-C1-4alkyl group, a C1-4alkoxy group, a C1-4alkylsulfonyl group or a C1-4alkylcarboxylic group. R2is preferably a hydroxy group, fluorine atom, chlorine atom, cyano group, oxo group, methyl group, ethyl group, methoxymethyl group, methoxy group, ethoxy group, methylsulfonyl group, ethylsulfonyl group or acetyl group. R2is particularly preferably a hydroxy group, fluorine atom, cyano group, methyl group, methoxymethyl group or methoxy group.

R2is a Deputy selected from the group consisting of a hydroxy group, a C1-4alkyl groups (where C1-4the alkyl group may be substituted by 1 or 2 C1-4alkoxy groups), (C1-4alkoxy group, halogen-C1-4alkyl group, a C1-4alkylsulfonyl group, C1-4alkylcarboxylic group, and-NR10aR10bwhen R2is a Deputy, predstavleniya nitrogen atom, B. forming R10aand R10bare as described above.

R2when he is Deputy to the nitrogen atom, forms a B preferably represents C1-4alkyl group, a C1-4alkylsulfonyl group or a C1-4alkylcarboxylic group. R2represents preferably a methyl group, methylsulfonyl group or acetyl group.

m is any integer from 0 to 3, preferably equal to any integer from 0 to 2 and more preferably 0 or 1.

Part of the structure containing B, represented by the following formula (IV):

also includes stereoisomeric structures that may exist.

Part of the structure represented by formula (IV)is preferably cyclopropyl group, tsiklogeksilnogo group, 4-hydroxycyclohexyl group, 3-methoxycyclohexyl group, 4-methoxycyclohexyl group, 4,4-diverticulectomy group, tetrahydrofuran-3-ilen group, 4-hydroxymitragynine-3-ilen group, 4-methoxyacridine-3-ilen group, tetrahydro-2H-Piran-2-ilen group, tetrahydro-2H-Piran-3-ilen group, tetrahydro-2H-Piran-4-ilen group, 4-hydroxycitrate-2H-Piran-2-ilen group, 5-hydroxyacetamido-2H-Piran-2-ilen group, 5-hydroxysteroid what-2H-Piran-3-ilen group, 4 cyanoacrylate-2H-Piran-4-ilen group, 3-Porterage-2H-Piran-3-ilen group, 4-Porterage-2H-Piran-4-ilen group, 3-methyltetrahydro-2H-Piran-3-ilen group, 4-methyltetrahydro-2H-Piran-4-ilen group, 2,2-dimethylether-2H-Piran-4-ilen group, 2,6-dimethylether-2H-Piran-4-ilen group, 3-methoxytyramine-2H-Piran-3-strong group, 4-methoxytyramine-2H-Piran-2-ilen group, 4-methoxytyramine-2H-Piran-4-ilen group, 5-methoxytyramine-2H-Piran-2-ilen group, 5-methoxytyramine-2H-Piran-3-ilen group, 4-exoterica-2H-Piran-3-ilen group, 3,6-dihydro-2H-Piran-4-ilen group, 5,6-dihydro-2H-Piran-3-ilen group, 1,4-dioxane-2-strong group, 5-methoxymethyl-1,4-dioxane-2-ilen group, 6-methoxymethyl-1,4-dioxane-2-ilen group, piperidine-4-ilen group, 1-methylpiperidin-4-ilen group, 1-(methylsulphonyl)piperidine-4-ilen group, piperazine-1-ilen group, 4-methylpiperazin-1-ilen group, 4-acetylpiperidine-1-ilen group, 4-(methylsulphonyl)piperazine-1-ilen group, morpholine-4-ilen group, morpholine-3-ilen group, 3-methylmorpholin-4-ilen group, 2,6-dimethylmorpholine-4-ilen group, 5-exmortis-2-ilen group, 4-methyl-5-oxo-morpholine-4-ilen group or 1,1-dissidocerida-2H-thiopyran-4-ilen group.

Part of the structure is a preferable tsiklogeksilnogo group, 4-hydroxycyclohexyl the ing group, 3-methoxycyclohexyl group, 4-methoxycyclohexyl group, 4,4-diverticulectomy group, tetrahydro-2H-Piran-2-ilen group, tetrahydro-2H-Piran-3-ilen group, tetrahydro-2H-Piran-4-ilen group, 4-hydroxycitrate-2H-Piran-2-ilen group, 5-hydroxyacetamido-2H-Piran-2-ilen group, 5-hydroxyacetamido-2H-Piran-3-ilen group, 4-cyanoacrylate-2H-Piran-4-ilen group, 3 Porterage-2H-Piran-3-ilen group, 4-Porterage-2H-Piran-4-ilen group, 3-methyltetrahydro-2H-Piran-3-ilen group, 4-methyltetrahydro-2H-Piran-4-ilen group, 2,2-dimethylether-2H-Piran-4-ilen group, 2,6-dimethylether-2H-Piran-4-ilen group, 3-methoxytyramine-2H-Piran-3-ilen group, 4-methoxytyramine-2H-Piran-2-strong group, 4-methoxytyramine-2H-Piran-4-ilen group, 5-methoxytyramine-2H-Piran-2-ilen group, 5-methoxytyramine-2H-Piran-3-ilen group, 4-exoterica-2H-Piran-3-ilen group, 3,6-dihydro-2H-Piran-4-ilen group, 5,6-dihydro-2H-Piran-3-ilen group, 1,4-dioxane-2-ilen group, 5-methoxymethyl-1,4-dioxane-2-strong group or 6-methoxymethyl-1,4-dioxane-2-ilen group.

R3and R4are the same or different and represent each a hydrogen atom, a halogen atom, a C1-4alkyl group, halogen-C1-4alkyl group or a cyano group. Preferably R3is the Wallpaper a hydrogen atom, fluorine atom, chlorine atom, cyano group or methyl group, and R4represents a hydrogen atom. More preferably R3represents a hydrogen atom or methyl group, and R4represents a hydrogen atom.

R5and R6are the same or different and represent each a hydrogen atom, halogen atom or C1-4alkyl group, or R5and R6together can form an oxo group, or together with the carbon atom to which R5and R6linked, can form a C3-8cycloalkyl group. Preferably R5and R6are the same or different and represent each a hydrogen atom, halogen atom or C1-4alkyl group. More preferably R5represents a hydrogen atom, fluorine atom or methyl group, and R6represents a hydrogen atom or a fluorine atom. Particularly preferably, R5represents a hydrogen atom, fluorine atom or methyl group, and R6represents a hydrogen atom.

Q is a bond or C1-4alkylenes group, more preferably a bond, methylene group or ethylene group, and particularly preferably a bond or methylene group.

Part of the structure containing Q, R5, R6and B, which presents imprint is the fact that formula (V):

also includes stereoisomeric structures that may be present.

Part of the structure represented by formula (V)is preferably cyclohexylmethyl group, 4-hydroxycyclohexyl group, 3-methoxycyclohexyl group, 4-methoxycyclohexyl group, 4,4-divorcecelebration group, tetrahydro-2H-Piran-2-ylmethylene group, tetrahydro-2H-Piran-3-ylmethylene group, tetrahydro-2H-Piran-4-ylmethylene group, 2-(tetrahydro-2H-Piran-4-yl)ethyl group, 2-fluoro-2-(tetrahydro-2H-Piran-4-yl)ethyl group, 2-(tetrahydro-2H-Piran-4-yl)through the group, tetrahydro-2H-Piran-3-ylmethylene group, 4-hydroxycitrate-2H-Piran-2-ylmethylene group, 5-hydroxyacetamido-2H-Piran-2-ylmethylene group, 5-hydroxyacetamido-2H-Piran-3-ylmethylene group, 4-cyanoacrylate-2H-Piran-4-ylmethylene group, 3-Porterage-2H-Piran-3-ylmethylene group, 4-Porterage-2H-Piran-4-ylmethylene group, 3-methyltetrahydro-2H-Piran-3-ylmethylene group, 4-methyltetrahydro-2H-Piran-4-ylmethylene group, 2,2-dimethylether-2H-Piran-4-ylmethylene group, 2,6-dimethylether-2H-Piran-4-ylmethylene group, 3-methoxytyramine-2H-Piran-3-ylmethylene group, 4-methoxytyramine-2H-Piran-2-ylmethylene group, 4-methoxytyramine-2H-Piran-4-ylmethylene group, 5-meth is sitetarget-2H-Piran-2-ylmethylene group, 5-methoxytyramine-2H-Piran-3-ylmethylene group, 4-exoterica-2H-Piran-3-ylmethylene group, 3,6-dihydro-2H-Piran-4-ylmethylene group, 2-(3,6-dihydro-2H-Piran-4-yl)ethyl group, 5,6-dihydro-2H-Piran-3-ylmethylene group, 2-(5,6-dihydro-2H-Piran-3-yl)ethyl group, 1,4-dioxane-2-ylmethylene group, 5-methoxymethyl 1,4-dioxane-2-ylmethylene group or 6-methoxymethyl-1,4-dioxane-2-ylmethylene group.

In the General formula (I) in a preferred combinations of parts of the structure represented by formula (III) and (V)when part of the structure represented by formula (III)represents 1H-indol-5-ilen group, 4-fluoro-1H-indol-5-ilen group, 6-fluoro-1H-indol-5-ilen group, 7-fluoro-1H-indol-5-ilen group, 7-fluoro-3-methyl-1H-indol-5-ilen group 7-fluoro-4-methyl-1H-indol-5-ilen group, 3,4-dimethyl-7-fluoro-1H-indol-5-ilen group, 1H-indazol-5-ilen group, 1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 6-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 6-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 6-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-chloro-4-methyl-1H-pyrrolo[2,3b]pyridine-5-ilen group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-methoxy-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-amino-1H-pyrrolo[2,3-b]pyridine-5-ilen group 4-amino-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 1H-pyrrolo[3,2-b]pyridine-5-ilen group, a pyrazolo[1,5-a]pyrimidine-6-ilen group, 1H-pyrazolo[3,4-b]pyridine-5-ilen group, 5H-pyrrolo[2,3-b]pyrazin-2-ilen group, 7H-pyrrolo[2,3-c]pyridazin-3-ilen group or 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, part of the structure represented by formula (V), is cyclohexylmethyl group, 4-hydroxycyclohexyl group, 3-methoxycyclohexyl group, 4-methoxycyclohexyl group, 4,4-divorcecelebration group, tetrahydro-2H-Piran-4-ylmethylene group, tetrahydro-2H-Piran-4-ylmethylene group, 2-(tetrahydro-2H-Piran-4-yl)ethyl group, 2-fluoro-2-(tetrahydro-2H-Piran-4-yl)ethyl group, 2-(tetrahydro-2H-Piran-4-yl)through the group, tetrahydro-2H-Piran-3-ylmethylene group, 4-hydroxycitrate-2H-Piran-2-ylmethylene group, 5-hydroxyacetamido-2H-Piran-2-ylmethylene group, 5-hydroxyacetamido-2H-Piran-3-ylmethylene group, 4-cyanoacrylate-2H-Piran-4-ylmethylene group, 3-Porterage-2H-Piran-3-ylmethylene group, 4-Porterage-2H-Piran-4-metallinou group, 3 methyltetrahydro-2H-Piran-3-ylmethylene group, 4-methyltetrahydro-2H-Piran-4-ylmethylene group, 2,2-dimethylether-2H-Piran-4-ylmethylene group, 2,6-dimethylether-2H-Piran-4-ylmethylene group, 3-methoxytyramine-2H-Piran-3-ylmethylene group, 4-methoxytyramine-2H-Piran-2-ylmethylene group, 4-methoxytyramine-2H-Piran-4-ylmethylene group, 5-methoxytyramine-2H-Piran-2-ylmethylene group, 5-methoxytyramine-2H-Piran-3-ylmethylene group, 4-exoterica-2H-Piran-3-ylmethylene group, 3,6-dihydro-2H-Piran-4-ylmethylene group, 2-(3,6-dihydro-2H-Piran-4-yl)ethyl group, 5,6-dihydro-2H-Piran-3-ylmethylene group, 2-(5,6-dihydro-2H-Piran-3-yl)ethyl group, 1,4-dioxane-2-ylmethylene group A 5-methoxymethyl-1,4-dioxane-2-ylmethylene group or 6-methoxymethyl-1,4-dioxane-2-ylmethylene group.

The following General formula (II) can be represented as another preferred variant implementation of the compounds represented by the General formula (I), in accordance with the present invention.

Here, in the General formula (II), B, Q, R2, R3, R4, R5, R6and m are as described above. Formula (IV) and (V)representing each part of the structure containing B in the General formula (II)are the same as described above.

In the General formula (II) Z represents C-R1dwhat does the nitrogen atom. R1drepresents a hydrogen atom, halogen atom or C1-4alkyl group and preferably a hydrogen atom, fluorine atom or methyl group.

R1a, R1band R1care the same or different and represent each a Deputy selected from the group consisting of a hydrogen atom, hydroxy group, halogen atom, cyano group, C1-4alkyl groups (where C1-4the alkyl group may be substituted by one or two identical or different C1-4alkoxy groups, or-NR7aR7b), C1-4alkoxy group, halogen-C1-4alkyl group, -NR7aR7b, -C(O)R8and-C(O)NR9aR9b. R7a, R7b, R8, R9aand R9bare as described above. Preferably R1a, R1band R1care the same or different and represent each a hydrogen atom, a halogen atom, a C1-4alkyl group or a C1-4alkoxy group and more preferably a hydrogen atom, fluorine atom, chlorine atom, methyl group or methoxy group. In a particular preferred combination of R1a, R1band R1c, R1aand R1bare the same or different and represent each a hydrogen atom, fluorine atom, chlorine atom or methyl group, and R1crepresents a hydrogen atom or a fluorine atom is.

Preferred examples of the compounds represented by the General formula (I) or (II)in accordance with the present invention include 6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 6-(7-fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 6-(3-chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 6-(3-chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-4-m is Teal-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 2,6-anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol, 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-1-[5-methyl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihyd is about-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol and 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol.

More preferred examples of the compounds include 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it, 6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it, 2,6-anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol, 2,6-anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol, 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-Exito is, 2,6-anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol and 2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol.

In the present invention, the phrase "its pharmacologically acceptable salt" refers to salts that can be obtained by converting compounds having the formula (I), in accordance with the present invention, which has a primary Deputy or contains a nitrogen atom in A and/or B in Sol conventional manner as desired.

Examples of such salts include salts of inorganic acids, such as hydrochloride, hydrobromide, sulphates, nitrates and phosphates, salts of carboxylic acids, such as acetates, fumarate, maleate, oxalates, malonate, succinate, citrates and malty; salts of sulfonic acids, such as methanesulfonate, econsultancy, benzosulfimide and toluensulfonate; and salts of amino acids such as glutamate and aspartate.

The compound or its pharmacologically acceptable salt, having the formula (I) in accordance with the present invention, can absorb moisture to absorb water or to form hydrate while letting in air or by recrystallization, and such hydrates are also included in the present invention.

The compound or its Pharma is logicheskie acceptable salt, having the formula (I) in accordance with the present invention, can form the MES in the interaction with the solvent or recrystallization; such a solvate is also included in the present invention.

In addition, the compound or its pharmacologically acceptable salt, having the formula (I) in accordance with the present invention may exist as stereoisomers; all isomers of the compounds and salts and mixtures of these isomers are included in the present invention.

The present invention also includes compounds labeled with various radioisotopes or non-radioactive isotopes.

The compound having the formula (I) in accordance with the present invention, can be easily obtained by the method described in parts of theMethod 1-3next. The connection may also be obtained without performing the diagrams on the stages of introduction and removal of the protective group.

(Method 1)

The connection represented by below formula (I)can be obtained in accordance with the following reaction scheme, for example.

In this scheme, R1, R2, R3, R4, R5, R6Q, A, B, m, and n are as described above.

Each stage inThe way1 will be shown below.

Compound 1 is converted into compound 2 by Rea is the reductive amination of compound 1 with a carbonyl compound, using known organic chemistry technique. The interaction is carried out by processing the connection 1 and the carbonyl compound by cyanoborohydride sodium, sodium borohydride or triacetoxyborohydride sodium in a suitable solvent that does not adversely influence the reaction such as methanol, dichloromethane or acetic acid), at from -20°C to 100°C, preferably from 0°C to 50°C, in the presence of a suitable acid (such as acetic acid, hydrochloric acid or triperoxonane acid), for example. The carbonyl compound may be used in excess of 1 mol, preferably from 1 to 5 moles, per mole of compound 1. The duration of the reaction varies from 5 minutes to 150 hours, usually from 15 minutes to 100 hours.

Compound 2 can also be obtained by alkylation reaction of compound 1, using known organic chemistry technique. Interaction perform processing connection 1 connection alkylhalides, connection methanesulfonylaminoethyl or similar compound in a suitable solvent that does not adversely influence the reaction such as N,N-dimethylformamide, dimethylsulfoxide, 1,4-dioxane or acetonitrile), or in a solvent consisting of a mixture thereof, at temperatures from 0°C to 300°C, preferably from the value at room temperature to 150°C,in the presence of an organic or inorganic base (such as potassium carbonate, tert-piperonyl potassium or triethylamine) with the addition of suitable substances, such as chloride of triethylenediamine), for example. Connection alkylamide, the connection of methanesulfonylaminoethyl or similar connection can be used in excess of 1 mol, preferably from 1 to 5 mol, per 1 mol of compound. The duration of the reaction varies from 1 minute to 72 hours, usually from 5 minutes to 48 hours.

Compound 1 is converted into compound 3 by the amidation reaction of compound 1 with a carbonyl compound using known organic chemistry technique. The reaction is carried out by the interaction of compound 1 with compound carboxylic acid in a suitable solvent that does not adversely influence the reaction such as benzene, toluene, diethyl ether, dichloromethane, tetrahydrofuran or N,N-dimethylformamide), or in a solvent consisting of a mixture thereof, at temperatures from -30°C up to the boiling point of the solvent used for the reaction, preferably from 0°C to 50°C, in the presence of a suitable condensing agent such as N,N-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or diethylthiophosphate. The condensing agent may be used in excess of 1 mol, preferably from 1 to 5 mol, MoE is ü connection 1. The interaction can also be carried out by adding a base (such as triethylamine, diisopropylethylamine, N-methylmorpholine or 4-dimethylaminopyridine). The amount of base may correspond to a catalytic or be redundant. The duration of reaction is from 10 minutes to 72 hours, usually from 30 minutes to 24 hours. The interaction may also be performed by the interaction of compound 1 with compound carboxylic acid halide in a suitable solvent that does not adversely impact on the interaction (such as benzene, toluene, diethyl ether, dichloromethane, tetrahydrofuran or dichloromethane), or in a solvent consisting of a mixture thereof, at temperatures from -30°C up to the boiling point of the solvent used for the reaction, preferably from 0°C to 100°C, in the presence of a suitable base (such as triethylamine, diisopropylethylamine, N-methylmorpholine or 4-dimethylaminopyridine). The base can be used in a catalytic amount or in excess. The duration of reaction is in the range from 10 minutes to 72 hours, usually from 30 minutes to 24 hours. Alternatively, the interaction may be carried out by the interaction of compound 1 with compound carboxylic acid in an acidic solvent (such as polyphosphoric acid) at t is mperature from 0°C to the boiling point of the solvent, used for the reaction, preferably from 10°C to 120°C. the Duration of the reaction is from 10 minutes to 72 hours, usually from 30 minutes to 24 hours.

In this scheme, Q1represents a methylene group. Compound 3 is converted into compound 2 by reduction reaction of compound 3, using a method known in the field of organic chemistry. The interaction is performed by treating compound 3 with a suitable regenerating agent (such as alumalite lithium, DIBORANE, lithium borohydride, complex, borane-tetrahydrofuran, or a complex of borane-dimethyl sulfide) in a suitable solvent that does not adversely influence the reaction such as dichloromethane, tetrahydrofuran, dichloromethane or toluene), or in a solvent consisting of a mixture thereof, at temperatures from -78°C to the boiling temperature used in the reaction, preferably from 0°C to 100°C, for example. Reducing agent may be used in excess of 1 mol, preferably from 1 to 5 mol, per mol of compound 3. The interaction performed by adding a Lewis acid (such as tin chloride or a complex of trevormoran-simple ether), if necessary. The duration of the reaction is from 1 minute to 60 hours, usually from 5 minutes to 24 hours.

Connection 2 conversions shall agree in connection 4 with the introduction of the carbonyl group in compound 2, using known organic chemistry technique. The interaction is performed by treating compound 2 1,1'-carbonyl diimidazol, carbonate N,N'-disuccinimidyl, triphosgene or similar substance in a suitable solvent that does not adversely influence the reaction (such as 1,4-dioxane, tetrahydrofuran or dichloromethane), or in a solvent consisting of a mixture thereof, at temperatures from -10°C to the boiling point of the solvent used for the reaction, preferably from 0°C to 100°C, for example. 1,1'-Carbonyldiimidazole, carbonate N,N'-disuccinimidyl, triphosgene or the like may be used in excess of 1 mol, preferably 1-5 mol, per mol of compound 2. The duration of the reaction is from 5 minutes to 60 hours, usually from 1 to 24 hours.

Compound 4 is converted into compound 5 by the reaction of a combination of compound 4 with compound forming part of a structure containing A, which is represented by the above formula (III), using known organic chemistry technique. The interaction is performed by treating compound 4 in the presence of the appropriate organoboronic acid, organoborane, ORGANOTIN, tsinkorganicheskih or magyarkanizsa connection and a suitable catalyst based on transition metal valence is thew (such as a compound of palladium), with the addition of organic or inorganic bases (such as sodium bicarbonate, tripotassium phosphate or diisopropylethylamine), ligand (such as triphenylphosphine) and is known for promoting the reaction of additives (such as lithium chloride or copper iodide), if necessary, for example.

The above reaction mix is carried out, using a suitable solvent that does not adversely influence the reaction such as N,N-dimethylformamide, tetrahydrofuran, toluene, 1,4-dioxane or water, or a solvent consisting of a mixture thereof, at a reaction temperature ranging from 0°C to 300°C, preferably from room temperature to 200°C. the above reaction is also carried out by treatment in a hermetically closed vessel or under microwave radiation. Organoboronic acid or a similar substance and the base can be used in excess of 1 mol, preferably from 1 to 5 mol, per mol of compound 3. The duration of the reaction varies from 1 minute to 60 hours, usually from 5 minutes to 24 hours.

(Method 2)

The compound represented by formula (I), shown below, can be, for example, obtained according to the following reaction scheme.

In this scheme, R1, R2, R3, R4, R5, R6, Q, A, B, m, and pavlata such as described above, and M represents alkalolu, borate or the like.

Each stage in the method 2 is shown below.

Compound 4 is converted into compound 6 using the exchange reaction of the halogen-metal compound 4, using known organic chemistry technique. The interaction is carried out, for example, by treating compound 4 in the presence of a suitable connection DIBORANE or ALCALDIA and a suitable catalyst based on transition metal (such as a compound of palladium), with the addition of an organic or inorganic base (such as potassium acetate, sodium carbonate or diisopropylethylamine), ligand (such as triphenylphosphine) and a known reaction promoting additive (such as lithium chloride or copper iodide), if necessary.

The above reaction is carried out using a suitable solvent that does not adversely influence the reaction such as N,N-dimethylformamide, tetrahydrofuran, toluene, 1,4-dioxane or water, or a solvent consisting of a mixture thereof, at a reaction temperature ranging from 0°C to 300°C, preferably from room temperature to 200°C. the above reaction is also carried out by treatment in a hermetically closed vessel or under microwave radiation. Diboronic or similar ve is estvo and base can be used in a quantity more than 1 mol, preferably from 1 to 5 mol, per mol of compound 4. The duration of the reaction is from 1 minute to 60 hours, usually from 5 minutes to 24 hours.

Interaction is also carried out by treating compound 4 with base, such as n-utility, second-utility or tert-utility in excess of 1 mol, preferably from 1 to 1.5 mol, in a suitable solvent that does not adversely influence the reaction such as benzene, toluene, diethyl ether or tetrahydrofuran), or in a solvent consisting of a mixture thereof, at temperatures from -100°C to 50°C, preferably from -85°C to 10°C, and subsequent interaction with metallogenica, such as the presence of TBT chloride, trialkylborane or the like. The duration of the reaction is from 1 minute to 24 hours, usually from 10 minutes to 8 hours.

Compound 6 is converted into compound 5 by the reaction of a combination of compound 6 with compound forming part of a structure containing A, which is represented by formula (III), using known organic chemistry technique. The interaction is realized by the processing of compound 6 in the presence of a suitable organohalogens connection and a suitable catalyst based on transition metal (such as connection palladium) with the addition of, for example, organic is about or inorganic bases (such as sodium bicarbonate, tripotassium phosphate or diisopropylethylamine), ligand (such as triphenylphosphine) and is known for promoting the reaction of the additive (such as lithium chloride or copper iodide), if necessary.

The above reaction mix is carried out, using a suitable solvent that does not adversely influence the reaction such as N,N-dimethylformamide, tetrahydrofuran, toluene, 1,4-dioxane or water, or a solvent consisting of a mixture thereof, at a reaction temperature from 0°C to 300°C, preferably from room temperature to 200°C. the above reaction is carried out by treatment in a hermetically closed vessel or under microwave radiation. Organoboronic acid or the like and the base is used in excess of 1 mol, preferably from 1 to 5 mol, per mol of compound 3. The duration of the reaction is from 1 minute to 60 hours, preferably from 5 minutes to 24 hours.

(Method 3)

The compound represented by formula (I)shown below, can be obtained, for example, in accordance with the following reaction schema.

In this scheme, R1, R2, R3, R4, R5, R6, Q, A, B, m, and n are as described above, and Pro represents a protective group.

Each stage in the method 3 is shown below.

Compound 1 is converted into compound 7 by the introduction of protective group (such as cyclohexanone group, trimethylsilylamodimethicone group, trimethylsilylethynyl group or cyanoethylene group) in the corresponding position of the compound 1, using known organic chemistry technique. For example, when Pro is cyclohexenone group interaction carried out by treating compound 1 ethyl 2-cyclohexanecarboxylate in a suitable solvent that does not adversely influence the reaction such as toluene, benzene or xylan), while heating under reflux. Ethyl 2-cyclohexanecarboxylate use in excess of 1 mol, preferably from 1 to 5 mol, per 1 mol of compound. The duration of the reaction is from 5 minutes to 150 hours, preferably from 60 minutes to 100 hours.

Compound 7 can be converted to compound 8 in accordance with the procedure of alkylation reaction, shown inthe way1. The reaction is also carried out by reaction Mitsunobu compound 7, using known organic chemistry technique. The reaction is carried out by the interaction of compound 7 with compound alcohol in a suitable solvent that does not adversely influence the reaction (such as benzo is, toluene, diethyl ether, dichloromethane or tetrahydrofuran), or in a solvent consisting of a mixture thereof, at temperatures from -30°C up to the boiling point of the solvent used for the reaction, preferably from 0°C to 50°C, in the presence of cyanomethaemoglobin or triphenylphosphine and a suitable reagent reaction Mitsunobu, such as diethylazodicarboxylate or diisopropylsalicylic. Triphenylphosphine and reagent reaction Mitsunobu use in excess of 1 mol, preferably from 1 to 5 mol, per mole of compound 7. The duration of reaction is from 10 minutes to 72 hours, preferably from 30 minutes to 24 hours.

Compound 8 can be converted to compound 9 in accordance with the procedure of the exchange reaction, the halogen-metal, shown inthe way2.

Compound 8 can be converted to Compound 10 in accordance with the procedure of combination reaction, shown inthe way1. Compound 9 can be converted to compound 10 and compound 6 can be converted to compound 5 in accordance with the procedure of combination reaction, shown inthe way2.

Compound 9 is converted into compound 6 and compound 10 is converted into connection the imposition of the 5 using the reaction of removing the protective group in compound 9 or 10, using known organic chemistry technique. For example, when Pro is cyclohexenone group interaction carried out by treating compound 9 or 10 of a suitable acid (such as sulfuric acid, hydrochloric acid or triperoxonane acid) in a suitable solvent that does not adversely influence the reaction such as ethanol, methanol, propanol or water), or in a solvent consisting of a mixture thereof, at a reaction temperature from 0°C to 200°C, preferably from room temperature to 150°C. the Acid is used in excess of 1 mol per mol of compound 9 or 10. The duration of the reaction is from 1 minute to 500 hours, preferably from 5 minutes to 200 hours.

The compound having the formula (I) in accordance with the present invention can also be obtained using the intermediate compound described in WO 2008/051493.

The compound or its pharmacologically acceptable salt, having the formula (I) in accordance with the present invention, used as the above-mentioned therapeutic agent or prophylactic agent can be administered orally in the form of tablets, capsules, granules, powder or syrup or introduced parenterally in the form of injections or suppositories, for example, alone or in mixture with a suitable pharmacologically acceptable ex what pienta, the diluent or the like.

These medicines get the well-known methods using additives such as excipients (examples of which include organic excipients such as sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbitol; starch derivatives such as corn starch, potato starch, α-starch and dextrin; cellulose derivatives such as crystalline cellulose; gum Arabic; dextran; & pullulan; and inorganic excipients such as silicate derivatives such as light silicic anhydride, converted aluminum silicate, calcium silicate and aluminometasilicate magnesium; phosphate, such as phosphate calcium; carbonates such as calcium carbonate; and sulfates such as calcium sulfate), lubricants (examples of which include stearic acid, and salts formed with metals and stearic acid such as calcium stearate and magnesium stearate; talc; colloidal silica; waxes such as veegum and spermaceti; boric acid; adipic acid; sulfates such as sodium sulfate; glycol; fumaric acid; sodium benzoate; DL-leucine; sodium salts of fatty acids; laurilsulfate, such as sodium lauryl sulfate and lauryl sulfate, magnesium; silicic acids such as silicic anhydride and silicic acid hydrate; and isaacanaya derivatives of starch), binders (examples of which include hydroxypropylcellulose, hypromellose, polyvinylpyrrolidone, macrogol, and compounds similar to the above excipients), dezintegriruetsja substances (examples of which include cellulose derivatives, such as nizkozameshhennoj hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose and cross-linked sodium carboxymethylcellulose; and chemically modified starches such as carboxymethyl-starch, carboxymethyl-starch sodium and cross-linked polyvinylpyrrolidon), stabilizers (examples of which include parahydroxybenzoate, such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenethyl alcohol; benzalconi chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; and sorbic acid), taste modifiers (examples of which include commonly used sweeteners, podnikatel and flavorings) and thinners.

The dose of a compound of the present invention can vary considerably depending on various conditions such as the activity of the substance and the symptoms, age and body weight of the patient (warm-blooded animal, in particular human). For oral administration of a single dose of the compound is preferably within the t is minimal, equal to 0.01 mg per kg of body weight, up to a maximum of 5000 mg / kg body weight, or intravenous single dose of the compound is in the range from a minimum of 0.001 mg per kg of body weight, up to a maximum of 5000 mg / kg of body weight, taken from one to several times a day depending on symptoms. The dose is preferably in the range from 0.1 mg per kg of body weight to 100 mg per kg of body weight per day.

EXAMPLES

The present invention will be described in more podrobno using the following examples, examples, and gathering examples of research; however, these examples are only illustrative and may be modified without departing from the scope of the present invention.

(Example 1)

1-(Cyclopropylmethyl)-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3(cyclopropylmethyl)pyridine-2,3-diamine

To a solution of 2,3-diamino-5-bromopyridine (1000 mg) in dichloromethane (25 ml) at room temperature was added acetic acid (304 μl) and cyclopropanecarboxaldehyde (406 ml), then was stirred for 1 hour. To the reaction solution under ice cooling was added tetrahydroborate sodium (604 mg) and the mixture was stirred with warming to room temperature for 22 hours. The reaction solution was extracted by adding feast upon the frame of an aqueous solution of sodium bicarbonate and dichloromethane. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was column purified flash chromatography with obtaining specified in the title compound (286 mg).

MS (ESI) m/z: 243 (M+H)+.

1H-NMR (CDCl3) δ: 0,24-0,30 (2H, m), 0,57-of 0.64 (2H, m), 1.06 a-1,19 (1H, m), 2,86-of 2.93 (2H, m)to 3.38 (1H, user. C)to 4.16 (2H, user. C)at 6.84 (1H, d, J=1,8 Hz), a 7.62 (1H, d, J=1,8 Hz).

Stage 2

6-Bromo-1-(cyclopropylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 1 (280 mg)in tetrahydrofuran (11 ml) was added 1,1'-carbonylbis-1H-imidazole (281 mg) and the mixture was heated under reflux for 8 hours. After cooling to room temperature the solvent was evaporated under reduced pressure. The obtained residue was led by addition of dichloromethane and hexane. This substance was collected by filtration, washed with hexane and then dried under reduced pressure to obtain specified in the title compound (273 mg).

MS (ESI) m/z: 268 (M+H)+.

1H-NMR (CDCl3) δ: 0,40 of 0.47 (2H, m), 0,58-of 0.64 (2H, m), 1,14-of 1.26 (1H, m), of 3.73 (2H, d, J=7,3 Hz), 7,38 (1H, d, J=1,8 Hz), 8,10 (1H, d, J=1,8 Hz), the remaining 9.08 (1H, user. C).

Stage 3

1-(Cyclopropylmethyl)-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

To a mixed solution of compounds poluchennogo is on the above stage 2 (41 mg), in a mixture of 1,4-dioxane is distilled water (1.6 ml - 0.4 ml) was added potassium carbonate (63 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (37 mg) and tetranitroaniline palladium (18 mg) and the mixture was heated under reflux at 170°C for 30 minutes using a microwave reactor. The reaction solution was cooled to room temperature and separated by adding ethyl acetate and distilled water. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by thin-layer chromatography (elwira a mixture of dichloromethane-methanol) to obtain the specified title compound (37 mg).

HRMS (ESI) [(M+H)+] calculated: C18H17N4O 305,14024; found: 305,14092.

1H-NMR (DMSO-d6) δ: 0,34-0,52 (4H, m), 1,21-1,32 (1H, m), of 3.78 (2H, d, J=6.9 Hz), 6,46-6,51 (1H, m), 7,37-7,44 (2H, m), of 7.48 (1H, d, J=8,3 Hz), to 7.84 (2H, DD, J=9,4, 1.8 Hz), to 8.20 (1H, d, J=1,8 Hz), 11,16 (1H, user. C)to 11.52 (1H, user. C).

(Example 2)

6-(1H-Indol-5-yl)-1-(tetrahydro-2H-Piran-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3-(tetrahydro-2H-Piran-4-yl)pyridine-2,3-diamine

2,3-Diamino-5-bromopyridine (1.0 g) and tetrahydro-4-Piran-4-one (0,69 g) was dissolved in acetic acid (20 ml). After stirring at room temperature during the course the e some time added tetrahydroborate sodium (0.6 g) and the mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated, diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was column purified flash chromatography (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (254 mg).

MS (ESI) m/z: 272 (M+H)+.

1H-NMR (CDCl3) δ: 1,50-and 1.54 (2H, m), 2,01-2,04 (2H, m), 3,15-3,18 (1H, m), 3,40-of 3.43 (1H, m), 3,52-3,55 (2H, m), 4,01-Android 4.04 (2H, m), 4,12-4,13 (2H, m), 6.90 to (1H, d, J=2.2 Hz), to 7.64 (1H, d, J=2.2 Hz).

Stage 2

6-Bromo-1-(tetrahydro-2H-Piran-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (167 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 1 (287 mg).

MS (ESI) m/z: 298 (M+H)+.

1H-NMR (CDCl3) δ: 1,80 of-1.83 (2H, m), 2,31-of 2.38 (2H, m), 3,54 is 3.57 (2H, m), 4,14-4,17 (2H, m), 4,58-to 4.62 (1H, m), 7,55 (1H, d, J=2.0 Hz), 8,11 (1H, d, J=2.0 Hz), of 9.51 (1H, user. C).

Stage 3

6-(1H-Indol-5-yl)-1-(tetrahydro-2H-Piran-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (10 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (48 mg).

HRMS (ESI) [(M+H)+] calculated: C19H19N4O2335,15080; ideno: 335,15316.

1H-NMR (DMSO-d6) δ: from 1.66 to 1.76 (2H, m), a 2.36-2.49 USD (2H, m), 3,49 (2H, t, J=11,0 Hz), 4,00 (2H, DD, J=11,0, 4,1 Hz), 4,45-4,56 (1H, m), 6,47-of 6.52 (1H, m), 7,37-7,44 (2H, m), of 7.48 (1H, d, J=8,3 Hz), 7,81 (1H, d, J=1,8 Hz), 7,84-7,88 (1H, m), 8,19 (1H, d, J=1,8 Hz), of 11.15 (1H, user. C)for 11.55 (1H, user. C).

(Example 3)

6-(1H-Indol-5-yl)-1-[2-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3-[2-(tetrahydro-2H-Piran-4-yl)ethyl]pyridine-2,3-diamine

Specified in the title compound (445 mg) was obtained in a way similar to stage 1 of example 2, using 2,3-diamino-5-bromopyridine (1.0 g) and tetrahydro-2H-Piran-4-ylacetamide (0,89 g).

MS (ESI) m/z: 300 (M+H)+.

Stage 2

6-Bromo-1-(tetrahydro-2H-Piran-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (707 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 1 (966 mg).

MS (ESI) m/z: 326 (M+H)+.

1H-NMR (CDCl3) δ: 1.32 to 1,71 (7H, m), 3,35-to 3.41 (2H, m), 3,89-3,91 (2H, m), 3,98-4,01 (2H, m), 7,30 (1H, d, J=2.0 Hz), to 8.12 (1H, d, J=2.0 Hz), 10,32 (1H, user. C).

Stage 3

6-(1H-Indol-5-yl)-1-[2-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (16 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (61 mg).

HRMS (ESI) [(M+H)+] calculated: C21H23N4O2363,18210; found: 363,18482.

1H-NMR (DMSO-d6) δ: 1,12-of 1.29 (2H, m), 1,45-of 1.73 (5H, m), 3,19-and 3.31 (2H, m), 3,76-of 3.96 (4H, m), 6,47-6,51 (1H, m), 7,38-the 7.43 (2H, m), of 7.48 (1H, d, J=8.7 Hz), 7,74 (1H, d, J=1,8 Hz), to 7.84 (1H, s), 8,19 (1H, d, J=1.8 Hz), 11,16 (1H, user. C)11,51 (1H, user. C).

(Example 4)

6-(1H-Indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the header connection (809 mg) was obtained as a colorless amorphous solid in a way similar to step 2 of example 1, using 5-bromo-N3-(tetrahydro-2H-Piran-4-ylmethyl)pyridine-2,3-diamine obtained by the method described in WO 2006/126081 (830 mg).

MS (FAB) m/z: 311M+.

1H-NMR (CDCl3) δ: 1,39-is 1.51 (2H, m), 1,55-to 1.67 (3H, m), 2.05 is-2,17 (1H, m)to 3.36 (2H, t, J=11.5 Hz), to 3.73 (2H, d, J=7,2 Hz), 3,99 (2H, DD, J=11,5, a 3.2 Hz), 7,31 (1H, d, J=1.7 Hz), to 8.12 (1H, d, J=1.7 Hz), 10,01 (1H, user. C).

Stage 2

6-(1H-Indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above stage 1 (50 mg), suspended in 1,4-dioxane (2 ml) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (39 mg), sodium carbonate (17 mg), tetrabutylammonium bromide (5 mg), tetranitroaniline palladium (18 mg) and water (1 ml). The mixture is agrawala with stirring in nitrogen atmosphere at 85°C during the night. The reaction solution was cooled to room temperature and separated by adding ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by thin-layer chromatography with silica gel (elwira a mixture of chloroform-methanol) to obtain the specified title compound (36 mg) as a colorless amorphous solid.

HRMS (ESI) [(M+H)+] calculated: C20H21N4O2349,16645; found: 349,16738.

(Example 5)

6-Quinoline-3-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (34 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (46 mg).

HRMS (ESI) [(M+H)+] calculated: C21H21N4O2361,16645; found: 361,16530.

1H-NMR (DMSO-d6) δ: 1,26-of 1.41 (2H, m), 1,47-of 1.57 (2H, m), 2.05 is-of 2.20 (1H, m), 3,19-3,30 (2H, m), 3,76-a 3.87 (4H, m), 7,63-7,71 (1H, m), 7,75-7,81 (1H, m), 8,03-to 8.12 (3H, m), to 8.45 (1H, d, J=1,8 Hz), 8,69 (1H, d, J=2.3 Hz), 9,31 (1H, d, J=2.3 Hz), 11,75 (1H, user. C).

(Example 6)

1-(Cyclohexylmethyl)-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3(cyclohexylmethyl)pyridine-2,3-diamine

Specified in the title compound (263 mg) was awarded with the special similar to the one used in stage 1 of example 1 using 2,3-diamino-5-bromopyridine (1.0 g) and cyclohexanecarboxaldehyde (591 mg).

MS (ESI) m/z: 284 (M+H)+.

1H-NMR (CDCl3) δ: 0,95-1,08 (2H, m), of 1.16 and 1.35 (4H, m), 1,67-of 1.88 (4H, m), 2,89 (2H, d, J=6.9 Hz), 4,11 (1H, user. C)the 5.51 (2H, user. C)7,13 (1H, d, J=1,8 Hz), to $ 7.91 (1H, d, J=1,8 Hz).

Stage 2

6-Bromo-1-(cyclohexylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (116 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 1 (260 mg).

1H-NMR (CDCl3) δ: 0,96-1,11 (2H, m), 1,14-of 1.35 (4H, m), 1,64-of 1.88 (4H, m), the 3.65 (2H, d, J=7,3 Hz), 4,15 (1H, user. C), 7,29 (1H, d, J=1,8 Hz), 8,07 (1H, d, J=1,8 Hz).

Stage 3

1-(Cyclohexylmethyl)-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (23 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (47 mg).

HRMS (ESI) [(M+H)+] calculated: C21H23N4O 347,18719; found: 347,18864.

1H-NMR (DMSO-d6) δ: 0,96-1,25 (6H, m), 1,55-1,71 (4H, m), 1.77 in-1,90 (1H, m), 3,71 (2H, d, J=7,3 Hz), 6,47-6,51 (1H, m), 7,37-the 7.43 (2H, m), of 7.48 (1H, d, J=8,3 Hz), 7,76 (1H, d, J=1,8 Hz), to 7.84 (1H, d, J=1,8 Hz), 8,18 (1H, d, J=1,8 Hz), 11,16 (1H, user. C)11,50 (1H, user. C).

(Example 7)

6-(1H-Indol-5-yl)-5-methyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-6-methyl-3-nitropyridine-2-amine

To a solution of 6-amino-3-bromo-2-methylpyridine (7.2 g) in concentrated sulfuric acid (39 ml) under cooling with ice for 30 minutes was added dropwise nitric acid (2.9 ml) and the mixture was stirred at the same temperature for one hour. After additional stirring at room temperature for one hour, the reaction solution was poured into ice-cold water. Added 50% aqueous sodium hydroxide solution and the precipitate was collected by filtration, washed with distilled water and then dried under reduced pressure to obtain specified in the title compound (9.0 g).

1H-NMR (CDCl3) δ: 2.57 m) (3H, s), 8,51 (1H, s).

Stage 2

5-Bromo-6-methylpyridine-2,3-diamine

Distillirovanna water (9 ml) and iron powder (to 21.6 g) was added to a solution of the compound obtained in the above stage 1 (8,9 mg)in ethanol (36 ml). Addition was added concentrated hydrochloric acid (0.4 ml) and the mixture was heated under reflux for one hour. Then was added iron powder (21,6 g) and the mixture was heated under reflux for one hour. The reaction solution was cooled to room temperature, filtered through celite 545 and washed with ethanol. The filtrate was concentrated under reduced pressure to obtain specified in the header is VCE compound (5.5 g).

1H-NMR (CDCl3) δ: 2,42 (3H, s), up 3.22 (2H, user. C)4,20 (2H, user. C), 7,03 (1H, s).

Stage 3

5-Bromo-6-methyl-N3-(tetrahydro-2H-Piran-4-ylmethyl)pyridine-2,3-diamine

Specified in the title compound (619 mg) was obtained in a way similar to stage 1 of example 1 using the compound obtained in the above stage 2 (1500 mg)and tetrahydro-2H-Piran-4-carbaldehyde (915 mg).

1H-NMR (CDCl3) δ: of 1.33 to 1.47 (2H, m), 1,68-to 1.77 (2H, m), 1,79-of 1.92 (1H, m), 2,42 (3H, s), 2,95 (2H, d, J=6.9 Hz), of 3.07 (1H, user. C), 3,37-of 3.46 (2H, m), 3,97-of 4.05 (2H, m), 4,11 (2H, user. C)6,91 (1H, s).

Stage 4

6-Bromo-5-methyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (462 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 3 (618 mg).

1H-NMR (CDCl3) δ: 1,37 of 1.50 (2H, m), 1,55-to 1.63 (2H, m), 2,03-to 2.18 (1H, m), 2,65 (3H, s), 3,31-to 3.41 (2H, m), 3,70 (2H, d, J=7,3 Hz), was 4.02-of 3.94 (2H, m), 7,32 (1H, s).

Stage 5

6-(1H-Indol-5-yl)-5-methyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (33 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (60 mg).

HRMS (ESI) [(M+H)+] calculated: C21H23N4O2363,18210; found: 363,18238.

1H-NMR (DMSO-d6) δ: ,18-1,33 (2H, m), 1,42-of 1.52 (2H, m), 1,94-of 2.08 (1H, m), is 2.37 (3H, s), 3,15-3,26 (2H, m), 3,66-and 3.72 (2H, m), 3,76-a-3.84 (2H, m), 6,47 (1H, user. C)to 7.09 (1H, d, J=8.7 Hz), 7,37-7,41 (2H, m), 7,46 (1H, d, J=8,3 Hz), 7,51 (1H, s), 11,16 (1H, user. C)11,40 (1H, user. C).

(Example 8)

6-(1H-Indol-5-yl)-7-methyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-4-methyl-3-nitropyridine-2-amine

To a solution of 5-bromo-4-methylpyridin-2-amine (2.0 g) in concentrated sulfuric acid (8.7 ml) at 55°C for 30 minutes was added dropwise nitric acid (0.7 ml) and the mixture was stirred at the same temperature for 3 hours. After additional stirring at room temperature for 2 hours, the reaction solution was poured into ice-cold water. Added 50% aqueous sodium hydroxide solution and the precipitate was collected by filtration, washed with distilled water and then dried under reduced pressure to obtain specified in the title compound (2.5 g).

MS (ESI) m/z: 268 (M+H)+.

1H-NMR (CDCl3) δ: 2,54 (3H, s), of 5.83 (2H, user. C)8,29 (1H, s).

Stage 2

5-Bromo-4-methylpyridine-2,3-diamine

Into a solution of the compound obtained in the above stage 1 (1354 mg)in ethanol (20 ml) was added distilled water (4 ml) and iron powder (3260 mg). Next was added concentrated hydrochloric acid (2.0 ml) and the mixture was heated under reflux for one what about the hours. The reaction solution was cooled to room temperature and then brought to pH 9 by addition of 1N. an aqueous solution of sodium hydroxide. The mixed solution was filtered through celite 545 and washed with ethanol. The filtrate was concentrated under reduced pressure to obtain specified in the connection header (934 mg).

1H-NMR (CDCl3) δ: 2,28 (3H, s), 3,39 (2H, user. C)4,10 (2H, user. C)to 7.77 (1H, s).

Stage 3

5-Bromo-4-methyl-N3-(tetrahydro-2H-Piran-4-ylmethyl)pyridine-2,3-diamine

Specified in the title compound (390 mg) was obtained in a way similar to stage 1 of example 1 using the compound obtained in the above stage 2 (1410 mg)and tetrahydro-2H-Piran-4-carbaldehyde (860 mg).

1H-NMR (CDCl3) δ: 1.32 to a 1.50 (2H, m), 1,71-of 1.81 (3H, m), 2,32 (3H, s), 2,73-and 2.79 (2H, m), 3,38-of 3.48 (2H, m), 3,98-4,06 (2H, m), 4.72 in (2H, user. C), 7,89 (1H, d, J=4,1 Hz).

Stage 4

6-Bromo-7-methyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (190 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 3 (288 mg).

MS (ESI) m/z: 326 (M+H)+.

1H-NMR (CDCl3) δ: 1,45-of 1.57 (4H, m), 1,89-2,04 (1H, m)2,60 (3H, s), 3,29-3,39 (2H, m), 3,93-a 4.03 (4H, m), 8,15 (1H, s), 8,77 (1H, user. C).

Stage 5

6-(1H-Indol-5-yl)-7-methyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Indicated the data in the title compound (33 mg) was obtained by way similar to the one used in stage 3 of example 1 using the compound obtained in the above stage 4 (92 mg).

HRMS (ESI) [(M+H)+] calculated: C21H23N4O2363,18210; found: 363,18512.

1H-NMR (DMSO-d6) δ: 1,21-of 1.37 (2H, m), 1,45-and 1.54 (2H, m), 1.91 a-2,07 (1H, m), 2,39 (3H, s), 3,21-to 3.33 (2H, m), 3,78-to 3.92 (4H, m), 6,44-of 6.49 (1H, m),? 7.04 baby mortality (1H, DD, J=8,3, 1,4 Hz), 7,38-7,42 (1H, m), 7,43-7,49 (2H, m), to 7.77 (1H, C), 11,19 (1H, user. C)11,53 (1H, user. C).

(Example 9)

6-(1H-Indol-5-yl)-1-{[1-(methanesulfonyl)piperidine-4-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

1-(Methanesulfonyl)piperidin-4-carbaldehyde

[1-(Methanesulfonyl)piperidine-4-yl]methanol obtained by the method described in US 2002/895374 (1,00 g), was dissolved in dichloromethane (20 ml). Added reagent dess-Martin (2,19 g) and the mixture was stirred at room temperature for one hour. To the reaction solution was added aqueous sodium thiosulfate solution and saturated aqueous sodium bicarbonate solution, then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure to obtain specified in the title compound (1.04 g).

Stage 2

5-Bromo-N3-{[1-(methanesulfonyl)piperidine-4-yl]methyl}pyridine-2,3-diamine

Specified in the title compound (92 mg) was obtained in a manner analogous to amend the momu in stage 1 of example 2, using 2,3-diamino-5-bromopyridine (0.75 g) and the compound obtained in the above stage 1 (0,99 g).

MS (ESI) m/z: 363 (M+H)+.

Stage 3

6-Bromo-1-{[1-(methanesulfonyl)piperidine-4-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (59 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 2 (92 mg).

MS (ESI) m/z: 389 (M+H)+.

Stage 4

6-(1H-Indol-5-yl)-1-{[1-(methanesulfonyl)piperidine-4-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (1.6 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in the above stage 3 (28 mg).

HRMS (ESI) [(M+H)+] calculated: C22H24N5O3S 426,15998; found: 426,16272.

(Example 10)

6-Quinoline-6-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (54 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (54 mg).

HRMS (ESI) [(M+H)+] calculated: C21H21N4O2361,16645; found: 361,16722.

1H-NMR (DMSO-d6) δ: 1,22-of 1.40 (2H, m), 1,46-of 1.56 (2H, m), 2,03-to 2.18 (1H, m), 3,18-3,30 (2, m), 3.75 to 3,86 (4H, m), 7,53-to 7.61 (1H, m), 8,01 (1H, d, J=1,8 Hz), 8.07-a 8,18 (2H, m), 8,31 (1H, d, J=1,8 Hz), of 8.37-to 8.45 (2H, m), 8,87-8,93 (1H, m), of 11.69 (1H, user. C).

(Example 11)

6-Isoquinoline-4-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (40 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg), and isoquinoline-4-elborow acid (37 mg).

HRMS (ESI) [(M+H)+] calculated: C21H21N4O2361,16645; found: 361,16727.

1H-NMR (DMSO-d6) δ: 1,19 is 1.34 (2H, m), 1,44-of 1.53 (2H, m), 1,95-2,12 (1H, m), 3,15-of 3.27 (2H, m), 3,70-of 3.85 (4H, m), 7,71-to 7.84 (3H, m), 7,86-a 7.92 (1H, m), of 8.04 (1H, d, J=1,8 Hz), 8,23 (1H, d, J=8,3 Hz), 8,49 (1H, s), 9,36 (1H with), 11,76 (1H, user. C).

(Example 12)

6-Quinoline-4-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (6 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg)and quinoline-4-elborow acid (37 mg).

HRMS (ESI) [(M+H)+] calculated: C21H21N4O2361,16645; found: 361,16471.

1H-NMR (DMSO-d6) δ: 1,21-of 1.36 (2H, m), USD 1.43-of 1.55 (2H, m), 1,95-2,12 (1H, m), 3,17-of 3.27 (2H, m), 3.72 points-a 3.87 (4H, m), 7,54 (1H, d, J=4.6 Hz), 7,60-7,66 (1H, m), 7,78-a 7.85 (2H, m), 7,94 (1H, d, J=8,3 Hz), 8,08 (1H, s), 8,13 (1H, d, J=8.7 Hz), 8,97 (1H, d, J=4.6 Hz), RS 11.80 (1H, user with).

(Example 13)

6-Quinoline-5-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (45 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg)and quinoline-5-elborow acid (37 mg).

HRMS (ESI) [(M+H)+] calculated: C21H21N4O2361,16645; found: 361,16582.

1H-NMR (DMSO-d6) δ: 1,20-of 1.35 (2H, m), 1,44-of 1.55 (2H, m), 1,97-2,11 (1H, m), 3,16-of 3.27 (2H, m), 3,70-3,86 (4H, m), 7,55 (1H, DD, J=8,7, 4,1 Hz), 7,60-to 7.64 (1H, m), 7,73 (1H, s), 7,82-7,89 (1H, m), 8,01 (1H, d, J=1,8 Hz), 8,09 (1H, d, J=8,3 Hz), 8,24 (1H, d, J=8,3 Hz), of 8.95 (1H, DD, J=4,1, 1,4 Hz), 11,74 (1H, user. C).

(Example 14)

6-(1H-Indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol

5-Bromo-1H-indazole (1,00 g) was dissolved in N,N-dimethylformamide (20 ml) was added bis(pinacolato)diboron (a 3.87 g), potassium acetate (2,49 g) and the complex [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride-dichloromethane (0.12 g). The mixture was stirred with heating under nitrogen atmosphere at 100°C during the night. The reaction solution was cooled to room temperature and then concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexa is) obtaining specified in the connection header (1,99 g).

MS (ESI) m/z: 245 (M+H)+.

Stage 2

6-(1H-Indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (9 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole obtained in the above stage 1 (49 mg).

HRMS (ESI) [(M+H)+] calculated: C19H20N5O2350,16170; found: 350,16170.

1H-NMR (DMSO-d6) δ: 1,21-of 1.39 (2H, m), 1,45-of 1.56 (2H, m), 2,02-2,17 (1H, m), 3,19-3,30 (2H, m), of 3.73-3,88 (4H, m), of 7.64 (1H, d, J=8.7 Hz), of 7.70 (1H, DD, J=8,7, and 1.4 Hz), 7,87 (1H, d, J=1,8 Hz), of 8.06 (1H, s)to 8.14 (1H, s), 8,23 (1H, d, J=1,8 Hz), 11,58 (1H, user. C).

(Example 15)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (45 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 4 (75 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (59 mg).

HRMS (ESI) [(M+H)+] calculated: C19H20N5O2350,16170; found: 350,16275.

1H-NMR (DMSO-d6) δ: 1,25-to 1.38 (2H, m)and 1.51 (2H, d, J=11.7 Hz), 2,10 (1H, user. C), 3,24 (2H, t, J=11.7 Hz), 3,74-3,86 (4H, m), of 6.49-6,53 (1H, m), 7,50-rate of 7.54 (1H, m), to $ 7.91 (1H, d, J=2.0 Hz), by 8.22 compared to 8.26 (2H, m), 8,55 (1H, d, J=2.0 Hz), 11,59 (1H, s), 11,74 (1H, s).

p> (Example 16)

6-(6-Methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (44 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (110 mg)and tert-butyl 6-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate obtained by the method described in WO 2007/135398 (151 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17844.

1H-NMR (DMSO-d6) δ: 1,17-of 1.35 (2H, m), 1,44-and 1.54 (2H, m), 1,95-2,11 (1H, m), 2,48 (3H, s), 3,15-3,30 (2H, m), 3,70-3,86 (4H, m), 6,40-6,44 (1H, m), 7,39-7,44 (1H, m), 7,62-7,66 (2H, m), 7,79 (1H, s), of 7.90 (1H, d, J=1,8 Hz), to 11.61 (1H, user. C)11,54 (1H, user. C).

(Example 17)

5-Methyl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (47 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 7 (80 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (66 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17731.

1H-NMR (DMSO-d6) δ: 1,19-of 1.33 (2H, m), 1.41 to a rate of 1.51 (2H, m), 1,95-2,10 (1H, m), of 2.38 (3H, s), 3,16-to 3.33 (2H, m), 3,66-a-3.84 (4H, m), 6,47-6,52 (H, m), 7,47 (1H, s), 7,51-of 7.55 (1H, m), of 7.96 (1H, d, J=1,8 Hz), 8,21 (1H, d, J=1,8 Hz), of $ 11.48 (1H, user. C)11,74 (1H, user. C).

(Example 18)

7-Methyl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (64 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 8 (88 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (72 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17698.

1H-NMR (DMSO-d6) δ: 1,22-of 1.37 (2H, m), 1,43-and 1.54 (2H, m), 1,92-2,07 (1H, m), 2,39 (3H, s), 3,26-of 3.43 (2H, m), 3,78-of 3.94 (4H, m), 6,47-of 6.52 (1H, m), 7,51-EUR 7.57 (1H, m), 7,80 (1H, s), to 7.93 (1H, d, J=1,8 Hz), 8,17 (1H, d, J=1,8 Hz), to 11.61 (1H, user. C)11,76 (1H, user. C).

(Example 19)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (46 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 2 of example 2 (61 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (55 mg).

HRMS (ESI) [(M+H)+] calculated: C18H18N5O2336,14605; found: 336,14456.

1H-NMR (DMSO-d6) δ: 1,66-of 1.75 (2H, m), 2,39-2,49 (2H, m), 3,42-of 3.53 (2H, m), 3.96 points-of 4.05 (2H, m), of 4.44-of 4.57 (1H, m), 6.48 in-6,53 (1H, m), 7,50-,55 (1H, m), to $ 7.91 (1H, d, J=1,8 Hz), 8,23 (1H, d, J=1,8 Hz), of 8.27 (1H, d, J=1,8 Hz), 8,55 (1H, d, J=1,8 Hz), are 11.62 (1H, user. C)11,74 (1H, user. C).

(Example 20)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-[2-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (36 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 2 of example 3 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (49 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17712.

1H-NMR (DMSO-d6) δ: 1,12-of 1.27 (2H, m), 1,42-of 1.56 (1H, m), 1,58-1,71 (4H, m), of 3.25 to 3.35 (1H, m), 3,76-a-3.84 (2H, m), 3,86-of 3.94 (2H, m), 6,48-of 6.52 (1H, m), 7,49-7,52 (1H, m), 7,81 (1H, d, J=2.3 Hz), 8,20 is 8.25 (2H, m), charged 8.52 (1H, d, J=2.3 Hz), 11,57 (1H, user. C)11,70 (1H, user. C).

(Example 21)

1-(Cyclopropylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (51 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 2 of example 1 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (60 mg).

HRMS (ESI) [(M+H)+] calculated: C17H16N5O 306,13548; found: 306,13866.

1H-NMR (DMSO-d6) δ: 0,39-0,54 (4H, m), 1,23-of 1.36 (1H, m), with 3.79 (2H, d, J=6.9 Hz), 6,50-6,55 (1H, m), 7,51-7,56 (1H, m), to 7.93 (1H, d, J=1.8 G is), 8,25-of 8.28 (2H, m), 8,56 (1H, d, J=1,8 Hz), to 11.61 (1H, user. C)of 11.75 (1H, user. C).

(Example 22)

1-(Tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H,3'H-6,6'-biomedico[4,5-b]pyridine-2-he

Into a solution of the compound obtained in stage 1 of example 5 (75 mg)in N,N-dimethylformamide (2.5 ml) was added bis(triphenylphosphine)palladium(II) dichloride (17 mg) and 6-(tributylstannyl)-3H-imidazo[4,5-b]pyridine obtained by the method described in WO 2008/051493 (75 mg)and the mixture was stirred at 110°C for 2 hours. The solvent of the reaction mixture was evaporated under reduced pressure. The obtained residue was purified by HPLC to obtain specified in the title compound (6 mg).

HRMS (ESI) [(M+H)+] calculated: C18H19N6O2351,15695; found: 351,15798.

1H-NMR (DMSO-d6) δ: 1,21-of 1.36 (2H, m), 1,45-and 1.54 (2H, m), 3,17-of 3.27 (2H, m), 3.72 points-3,86 (4H, m), 6,56-of 6.61 (1H, m), 7,95 (1H, d, J=1.7 Hz), of 8.27 (2H, d, J=1.7 Hz), 8,30 (1H, user. C)of 8.47 (1H, s), 8,69 (1H, d, J=2.3 Hz).

(Example 23)

6-(1H-Indol-2-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (23 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg), and [1-(tert-butoxycarbonyl)-1H-indol-2-yl]boronic acid (55 mg).

HRMS (ESI) [(M+H)+] calculated: C20H21N4O2349,16645; found is: 349,16844.

1H-NMR (DMSO-d6) δ: 1,26-to 1.38 (2H, m), 1,47-of 1.55 (2H, m), 2,03-to 2.15 (1H, m), 3,17-3,29 (2H, m), of 3.73 (2H, d, J=7,4 Hz), 3,79-a 3.87 (2H, m)6,94 (1H, d, J=1.7 Hz), 6,97-7,01 (1H, m), 7,05-7,11 (1H, m), 7,37-7,42 (1H, m), 7,51 (1H, d, J=7,4 Hz), to 7.93 (1H, d, J=1.7 Hz), 8,44 (1H, d, J=1.7 Hz), 11,50 (1H, user. C).

(Example 24)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-[1-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3-[1-(tetrahydro-2H-Piran-4-yl)ethyl]pyridine-2,3-diamine

2,3-Diamino-5-bromopyridine (1.07 g) and 1-(tetrahydro-2H-Piran-4-yl)alanon (0,80 g) was dissolved in methanol (20 ml) was added acetic acid (0,98 ml). After stirring at room temperature for some time added cyanoborohydride sodium (1.08 g) and the mixture was stirred at room temperature for 20 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate. Next, the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was column purified flash chromatography (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (334 mg).

MS (ESI) m/z: 300 (M+H)+.

Stage 2

6-Bromo-1-[1-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (345 mg) was obtained by way of analogichnym used in stage 2 of example 1, using the compound obtained in the above stage 1 (344 mg).

MS (ESI) m/z: 326 (M+H)+.

1H-NMR (CDCl3) δ: of 1.27 to 1.31 (1H, m), of 1.52 (3H, d, J=7,1 Hz), 1,77-of 1.81 (1H, m), 2,16-2,19 (1H, m), 3,29-of 3.31 (1H, m), 3,40-of 3.43 (1H, m), 3,90-to 3.92 (1H, m), 4.04 the-4,06 (1H, m), 4,15-4,17 (1H, m), 7,39 (1H, d, J=2.0 Hz), 8,10 (1H, d, J=2.0 Hz), a 9.35 (1H, s).

Stage 3

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-[1-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (33 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (49 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17814.

1H-NMR (DMSO-d6) δ: 1,11-1,20 (2H, m), of 1.24 to 1.37 (1H, m), for 1.49 (3H, d, J=6.9 Hz), 1,72-to 1.82 (1H, m), 2.26 and-2,40 (1H, m), 3,09-is 3.21 (1H, m), 3,28-to 3.33 (1H, m), 3,71-with 3.79 (1H, m), 3,86-of 3.95 (1H, m), 4,11-4,22 (1H, m), of 6.49-6,53 (1H, m), 7,50-rate of 7.54 (1H, m), of 7.90 (1H, d, J=1,8 Hz), 8,24 (2H, DD, J=11,9, 1.8 Hz), 8,54 (1H, d, J=2.3 Hz), 11,58 (1H, user. C)11,73 (1H, user. C).

(Example 25)

1-[(4-Methyltetrahydro-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

4 Methyltetrahydro-2H-Piran-4-carbaldehyde

(4 Methyltetrahydro-2H-Piran-4-yl)methanol obtained by the method described in EP 1431285 (1,02 g), was dissolved in dichloromethane (20 ml). Added dimethylsulfate the (5,01 ml), the triethylamine (5,46 ml) and a complex of a sulfur trioxide-pyridine (3,74 g) and the mixture was stirred at room temperature for one hour. To the reaction solution was added saturated aqueous solution of ammonium chloride, then extracted with chloroform. The organic layer is washed with 1 N. hydrochloric acid, saturated aqueous sodium bicarbonate and saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain specified in the header of the compound (647 mg).

Stage 2

5-Bromo-N3-[(4-methyltetrahydro-2H-Piran-4-yl)methyl]pyridine-2,3-diamine

Specified in the title compound (574 mg) was obtained in a way similar to stage 1 of example 24, using 2,3-diamino-5-bromopyridin of 0.85 g) and the compound obtained in the above stage 1 (0.64 g).

MS (ESI) m/z: 300 (M+H)+.

Stage 3

6-Bromo-1-[(4-methyltetrahydro-2H-Piran-4-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (636 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 2 (574 mg).

MS (ESI) m/z: 326 (M+H)+.

1H-NMR (CDCl3) δ: 1.14 in (3H, s), 1,36-of 1.39 (2H, m), 1,68 is 1.75 (2H, m), 3,61-the 3.65 (2H, m), 3,83-3,86 (2H, m), Android 4.04 (2H, s), 7,32 (1H, d, J=2.0 Hz), 8,10 (1H, d, J=2.0 Hz), a 9.35 (1H, s).

Stage 4

1-[(4-Methyltetrahydro-2H-Piran-4 and is)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (36 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (49 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17621.

1H-NMR (DMSO-d6) δ with 1.07 (3H, s), of 1.26 and 1.35 (2H, m), 1,57 is 1.70 (2H, m), 3.46 in of 3.56 (2H, m), 3,66-of 3.80 (4H, m), 6.48 in-6,54 (1H, m), 7,50-of 7.55 (1H, m), 7,88 (1H, s), 8,20 compared to 8.26 (2H, m), 8,53 (1H, s), are 11.62 (1H, user. C)11,74 (1H, user. C).

(Example 26)

1-{[1-(Methanesulfonyl)piperidine-4-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (4.3 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in stage 3 of example 9 (28 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (21 mg).

HRMS (ESI) [(M+H)+] calculated: C22H23N6O3S 427,15523; found: 427,15738.

(Example 27)

6-(4-Fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

4-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

5-Bromo-4-fluoro-1H-indole, obtained by the method described in Eur. J. Org. Chem. 2956-2969, 2006 (793 mg), was dissolved in N,N-dimethylformamide (30 ml) and EXT is ulali bis(pinacolato)diboron (1.88 g), potassium acetate (1,82 g) and the complex [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride-dichloromethane (151 mg). The mixture was stirred with heating under nitrogen atmosphere at 100°C during the night. The reaction solution was cooled to room temperature and then concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane). The obtained colorless oil in suspension were washed with hexane to obtain specified in the title compound (481 mg) as colorless solids.

MS (EI) m/z: 261 M+.

1H-NMR (CDCl3) δ: to 1.38 (12H, s), 6,65 of 6.68 (1H, m), 7,14-7,17 (1H, m), 7,18 (1H, s), 7,51 (1H, DD, J=8,3, 5,5 Hz), of 8.27 (1H, user. C).

Stage 2

6-(4-Fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (35 mg) was obtained as a colorless amorphous solid in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 4 (50 mg)and the compound obtained in the above stage 1 (46 mg).

HRMS (ESI) [(M+H)+] calculated: C20H20FN4O2367,15703; found: 367,15767.

1H-NMR (DMSO-d6) δ: 1,24-of 1.35 (2H, m), 1,50 (2H, d, J=11.7 Hz), 2,00-2,11 (1H, m), 3,23 (2H, t, J=11.7 Hz in), 3.75 (2H, d, J=6.9 Hz), 3,82 (2H, DD, J=11,7, 2,8 Hz), 6,54-6,56 (1H, m), 7,22 (1H, t, J=8.0 Hz), 7,34 (1H, d, J=8.0 Hz), 7,44 (1H, t, J=2,8 Hz), 7,71 (1H, s), 8,07 (1H, t, J=1,6 Hz), of $ 11.48 (1H, s), of 11.61 (1H, s).

(Example 28)

6-(6-Fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

Specified in the title compound (867 mg) was obtained as colorless solid by the method similar to those used in stage 1 of example 27 using 5-bromo-6-fluoro-1H-indole, obtained by the method described in Eur. J. Org. Chem. 2956-2969, 2006 (1.22 g).

MS (EI) m/z: 261 M+.

1H-NMR (CDCl3) δ: to 1.38 (12H, s), 6,53 (1H, s),? 7.04 baby mortality (1H, d, J=10.1 Hz), 7,17 (1H, t, J=2,6 Hz), of 8.04 (1H, d, J=5.5 Hz), 8,17 (1H, user. C).

MS (ESI) m/z: 262 (M+H)+.

Stage 2

6-(6-Fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (35 mg) was obtained as a colorless amorphous solid in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 4 (50 mg)and 6-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole obtained in the above stage 1 (46 mg).

HRMS (ESI) [(M+H)+] calculated: C20H20FN4O2367,15703; found: 367,15850.

1H-NMR (DMSO-d6) δ: 1,22-of 1.35 (2H, m), for 1.49 (2H, d, J=11.5 Hz), 2,04 (1H, user. C)is 3.21 (2H, t, J=11.5 Hz), 3,74 (2H, d, J=7,3 Hz), 3,81 (2H, d, J=11.5 Hz), 6.48 in (1H, s), 7,29 (1H, d, J=11.5 Hz), 7,38 (1H, t, J=2,8 Hz), the 7.65 (1H, d, J=8,3 Hz), 7,68 (1H, s, of 8.04 (1H, s), 11,21 (1H, s), 11,60 (1H, s).

(Example 29)

6-(7-Fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

7-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

Specified in the title compound (189 mg) was obtained in the form of a solid white color way, similar to the one used in stage 1 of example 27 using 5-bromo-7-fluoro-1H-indole, obtained by the method described in Eur. J. Org. Chem. 2956-2969, 2006 (0,596 g).

MS (EI) m/z: 261 M+.

1H-NMR (CDCl3) δ: to 1.38 (12H, s), 6,53 (1H, s),? 7.04 baby mortality (1H, d, J=10.1 Hz), 7,17 (1H, t, J=2,6 Hz), of 8.04 (1H, d, J=5.5 Hz), 8,17 (1H, user. C).

Stage 2

6-(7-Fluoro-1H-indol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (41 mg) was obtained as a colorless amorphous solid in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 4 (50 mg)and the compound obtained in the above stage 1 (48 mg).

HRMS (ESI) [(M+H)+] calculated: C20H20FN4O2367,15703; found: 367,15743.

1H-NMR (DMSO-d6) δ: 1,26-of 1.39 (2H, m)and 1.51 (2H, d, J=11.7 Hz), 2,10 (1H, user. C), 3,24 (2H, t, J=11.7 Hz), of 3.78 (2H, d, J=7,2 Hz), 3,83 (2H, d, J=11.7 Hz), 6,59 (1H, s), 7,32 (1H, d, J=a 12.7 Hz), 7,46 (1H, t, J=2.4 Hz), 7,72 (1H, s), 7,87 (1H, d, J=1.5 Hz), 8,24 (1H, d, J=1.5 Hz), to 11.56 (1H, s), 11,67 (1H, s).

(Example 30)

6-(2-Oxo-2,3-di is Idro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridine-2-he

Specified in the title compound (39 mg) was obtained as colorless solid by the method similar to those used in stage 1 of example 27 using 5-bromo-1,3-dihydro-2H-pyrrolo[2,3-b]pyridine-2-it is obtained by the method described in J. Am. Chem. Soc. 14426, 2006 (300 mg).

MS (EI) m/z: 260 M+.

1H-NMR (CDCl3) δ: of 1.35 (12H, s), 3,55 (2H, s), to 7.84 (1H, d, J=1.4 Hz), 8,53-8,55 (1H, m), 8,67 (1H, user. C).

Stage 2

6-(2-Oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (22 mg) was obtained as a colorless amorphous solid in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 4 (38 mg)and the compound obtained in the above stage 1 (33 mg).

HRMS (ESI) [(M+H)+] calculated: C19H20N5O3366,15661; found: 366,15792.

1H-NMR (DMSO-d6) δ: 1,25-to 1.38 (2H, m), for 1.49 (2H, d, J=11.7 Hz), 2,02 with 2.14 (1H, m), 3,23 (2H, t, J=11.7 Hz), 3,63 (2H, in), 3.75 (2H, d, J=7,2 Hz), 3,82 (2H, d, J=11.7 Hz), to 7.84 (1H, d, J=1.7 Hz), 7,92 (1H, s), 8,19 (1H, d, J=1.7 Hz), 8,40 (1H, d, J=1.7 Hz), 11,09 (1H, s), are 11.62 (1H, s).

(Example 31)

1-(5,6-Dihydro-2H-Piran-3-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3-(5,6-dihydro-2H-Piran-3-ylmethyl)pyridine-2,3-diamine

Specified in the title compound (434 mg) was obtained in a way similar to stage 1 of example 24, using 2,3-diamino-5-bromopyridin of 0.85 g) and 5,6-dihydro-2H-Piran-3-carbaldehyde obtained by the method described in US 4532337 (0,58 g).

MS (ESI) m/z: 284 (M+H)+.

Stage 2

6-Bromo-1-(5,6-dihydro-2H-Piran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (290 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 1 (434 mg).

MS (ESI) m/z: 310 (M+H)+.

1H-NMR (CDCl3) δ: 2,18-2,19 (2H, m in), 3.75 (2H, t, J=5.5 Hz), 4,06-4,06 (2H, m), 4,34-4,37 (2H, m), of 5.84-to 5.85 (1H, m), 7,30 (1H, d, J=2.0 Hz), 8,11 (1H, d, J=2.0 Hz), 9,12-to 9.15 (1H, m).

Stage 3

1-(5,6-Dihydro-2H-Piran-3-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (33 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (47 mg).

HRMS (ESI) [(M+H)+] calculated: C19H18N5O2348,14605; found: 348,14610.

1H-NMR (DMSO-d6) δ: 1,97-of 2.08 (2H, m), to 3.58-of 3.64 (2H, m)4,00 (2H, d, J=1,8 Hz), and 4.40 (2H, s), 5,77 (1H, s), 6.48 in-6,53 (1H, m), 7,50-of 7.55 (1H, m), to 7.77 (1H, d, J=1.8 Hz), 8,20-of 8.27 (2H, m), 8,49-8,53 (1H, m), 11,66 (1H, user. C)11,74 (1H, user. C).

(Example 32)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N3-(tetrahydro-2H-Piran-3-ylmethyl)pyridine-2,3-diamine

Specified in the title compound (743 mg) was obtained in a way similar to stage 1 of example 27, using 2,3-diamino-5-bromopyridine (2.00 g) and tetrahydro-2H-Piran-3-carbaldehyde obtained by the method described in US 5071863 (1,34 g).

MS (ESI) m/z: 286 (M+H)+.

Stage 2

6-Bromo-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the header connection (741 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 1 (743 mg).

MS (ESI) m/z: 312 (M+H)+.

1H-NMR (CDCl3) δ: 1,42 was 1.43 (1H, m), 1,58-to 1.61 (1H, m), 1,71-1,72 (1H, m), 1,80 of-1.83 (1H, m), 2,16-2,17 (1H, m)to 3.33 (1H, DD, J=11,5, 8,3 Hz), 3,50 of 3.56 (1H, m), of 3.77-of 3.80 (4H, m), 7,12 (1H, d, J=0.7 Hz), 7,34 (1H, d, J=2.0 Hz), 8,11 (1H, d, J=2.0 Hz).

Stage 3

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (33 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (60 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxanone the EN-2-yl)-1H-pyrrolo[2,3-b]pyridine (47 mg).

HRMS (ESI) [(M+H)+] calculated: C19H20N5O2350,16330; found: 350,16330.

1H-NMR (DMSO-d6): of 1.24 to 1.37 (1H, m), 1,38-is 1.51 (1H, m), 1,58-to 1.67 (1H, m), 1,68-of 1.78 (1H, m), 2,04-2,17 (1H, m), 3,19 of 3.28 (2H, m), 3,65-3,81 (4H, m), 6.48 in-6,54 (1H, m), 7,50-of 7.55 (1H, m), 7,88 (1H, d, J=1,8 Hz), 8,24 (2H, d, J=1,8 Hz), 8,54 (1H, d, J=2.3 Hz), 11,60 (1H, user. C)11,74 (1H, user. C).

(Example 33)

6-(7-Fluoro-1H-indol-5-yl)-1-(2-morpholine-4-retil)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

N-(2-Amino-5-bromopyridin-3-yl)-2-morpholine-4-ylacetamide

2,3-Diamino-5-bromopyridine (2.00 g) and morpholine hydrochloride-4-luxusni acid obtained by the method described in US 6352993 (1,34 g), was dissolved in acetonitrile (15 ml). Was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.22 g), 1-hydroxybenzotriazole (0,98 g) and N-methylmorpholin (1,29 ml) and the mixture was stirred at room temperature overnight. The reaction solution was diluted with chloroform and washed with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The obtained solid was washed with diethyl ether obtaining specified in the title compound (1.40 g) as a solid light yellow color.

MS (ESI) m/z: 315 (M+H)+.

1H-NMR (DMSO-d6) δ: 2,52 (4H, t, J=4.6 Hz), 3,62 (4H, t, J=4.6 Hz), 6,01 (2H, s), to 7.84 (1H, d, J=2.2 Hz), 7,87 (1H, d, J=2.2 G is), to 9.20 (1H, s).

Stage 2

5-Bromo-N3-(2-morpholine-4-retil)pyridine-2,3-diamine

Alumoweld lithium (120 mg) suspended in tetrahydrofuran (10 m). A solution of the compound obtained in the above stage 1 (500 mg)in tetrahydrofuran (3 ml) was slowly added dropwise with stirring at 0°C, then was stirred for one hour. Added alumoweld lithium (120 mg) and the mixture was stirred at room temperature for 2.5 hours and then was heated under reflux for one hour. The reaction solution was left to cool to room temperature and then added water (0.3 ml), 15% aqueous sodium hydroxide solution (0.3 ml) and water (0.6 ml). The precipitated insoluble substance was filtered through celite. The filtrate was concentrated to obtain specified in the title compound (397 mg).

MS (ESI) m/z: 301 (M+H)+.

Stage 3

6-Bromo-1-(2-morpholine-4-retil)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (79 mg) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 2 (397 mg).

MS (ESI) m/z: 327 (M+H)+.

Stage 4

6-(7-Fluoro-1H-indol-5-yl)-1-(2-morpholine-4-retil)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (2.8 mg) was obtained as colorless amorphous solids method, and the logic used in stage 2 of example 4, using the compound obtained in the above stage 3 (79 mg)and the compound obtained in stage 1 of example 29 (54 mg).

HRMS (ESI) [(M+H)+] calculated: C20H21FN5O2382,16793; found: 382,16871.

(Example 34)

6-(4-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (26 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 4 (60 mg)and [4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]boronic acid obtained by the method described in Tetrahedron Lett. (45), 2317-2319, 2004 (75 mg).

HRMS (ESI) [(M+H)+] calculated: C19H19Cl1N5O2; found: 384,12663.

1H-NMR (DMSO-d6) δ: of 1.20 to 1.37 (2H, m), 1,46-and 1.54 (2H, m), 1,99-to 2.15 (1H, m), 3,19 of 3.28 (2H, m), 3,70-a 3.87 (4H, m), 6,55-6,59 (1H, m), of 7.64-7.68 per (1H, m), 7,72 (1H, d, J=1.7 Hz), 8,01 (1H, d, J=1.7 Hz), compared to 8.26 compared to 8.26 (1H, m), of 11.69 (1H, user. C)to 12.13 (1H, user. C).

(Example 35)

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

tert-Butyl 5-bromo-3-chloro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

5-Bromo-3-chloro-1H-pyrrolo[2,3-b]pyridine (235 mg) was dissolved in dichloromethane (5 ml). Added ditretbutyl dicarbonate (248 mg) and N,N-dimethylaminopyridine (1.2 mg) and the mixture p is remedial at room temperature over night. The reaction solution was concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (297 mg).

MS (ESI) m/z: 331 (M+H)+.

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), the 7.65 (1H, s), with 8.05 (1H, d, J=2.2 Hz), 8,58 (1H, d, J=2.2 Hz).

Stage 2

6-Bromo-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

2,3-Diamino-5-bromopyridine (50 g) and ethyl ester of 2-cyclohexanecarbonyl acid (63.5 ml) was heated under reflux in xylene (2000 ml) for 64 hours. The reaction solution was cooled to room temperature and the precipitated crystals were collected by filtration. The resulting crude crystals are recrystallized from toluene to obtain specified in the title compound (30 g).

MS (ESI) m/z: 294 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,61-of 1.64 (2H, m), 1,72 is 1.75 (2H, m), 2,19-of 2.21 (2H, m), 2,31 of-2.32 (2H, m), of 5.89-5,90 (1H, m)to 7.50 (1H, d, J=2.0 Hz), 8,02 (1H, d, J=2.0 Hz), 11,34 (1H, s).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above step 2 (1 g), tetrahydro-2H-Piran-4-ylmethanol (0,43 g) and triphenylphosphine (1.1 g) was dissolved in tetrahydrofuran (30 ml). Dropwise under nitrogen atmosphere was added diisopropylethylamine (0,74 ml) and then the mixture was stirred at room temperature is f for 30 minutes. The reaction solution was concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (0,89 g).

MS (ESI) m/z: 392 (M+H)+.

1H-NMR (CDCl3) δ: 1,44-1,49 (2H, m), 1.61 of the tariff-1.62 (2H, m), 1,73-to 1.77 (2H, m), 1.85 to a 1.88 (2H, m), 2,10-2,12 (1H, m), 2,30 of-2.32 (2H, m), 2,39 is 2.44 (2H, m), 3,35-to 3.38 (2H, m), of 3.73 (2H, d, J=7,3 Hz), 3,97-4,00 (2H, m), 6,00-6,02 (1H, m), 7,28 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=2.0 Hz).

Stage 4

3-Cyclohex-1-EN-1-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Bis(pinacolato)diboron (925 mg), potassium acetate (715 mg) and the complex [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride-dichloromethane (93 mg) was added to a solution of the compound obtained in the above stage 3 (893 mg) in N,N-dimethylformamide (20 ml), and the mixture was heated with stirring in a nitrogen atmosphere at 80°C for 6.5 hours. The reaction solution was cooled to room temperature, diluted with ethyl acetate and washed with saturated saline solution. The organic layer was dried and then concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (723 mg).

MS (ESI) m/z: 440 (M+H)+.

1H-NMR (CDCl3) δ: of 1.36 (12H, s)of 1.45 to 1.48 (2H, m), 1,58-to 1.61 (2H, m), 1,5-or 1.77 (2H, m), 1,84-1,89 (2H, m), 2,12 with 2.14 (1H, m), 2,31 of-2.32 (2H, m), 2,43 is 2.43 (2H, m), 3.33 and-3,39 (2H, m), of 3.77 (2H, d, J=7,3 Hz), 3.96 points-to 3.99 (2H, m), 6,00-of 6.02 (1H, m), of 7.48 (1H, d, J=1.2 Hz), to 8.45 (1H, d, J=1.2 Hz).

Stage 5

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (60 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (120 mg)and the compound obtained in the above stage 1 (95 mg).

MS (ESI) m/z: 464 (M+H)+.

1H-NMR (CDCl3) δ: 1,45-of 1.56 (2H, m), 1,62 was 1.69 (2H, m), 1,75-of 1.81 (2H, m), 1,87-of 1.92 (2H, m), 2.13 and amounts to 2.24 (1H, m), 2,31-of 2.38 (2H, m), 2,46 of $ 2.53 (2H, m), 3.33 and-to 3.41 (2H, m), a-3.84 (2H, d, J=7,4 Hz), 3.95 to as 4.02 (2H, m), 6,06-6,10 (1H, m), 7,37 (2H, d, J=1.7 Hz), 8,07 (1H, d, J=1.7 Hz), 8,29 (1H, d, J=2.3 Hz), 8,54 (1H, d, J=2.3 Hz), to 8.94 (1H, user. C).

Stage 6

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 5 (58 mg)in ethanol (5 ml) was added distilled water (1.5 ml) was added under ice cooling concentrated sulfuric acid (1.5 ml). The reaction solution was stirred at 70°C for 89 hours. After cooling to room temperature the reaction solution was poured into saturated aqueous sodium bicarbonate solution and unnecessary substance was filtered. The obtained filtrate was divided is by adding ethyl acetate and distilled water. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was led from a solvent consisting of a mixture of dichloromethane and hexane, and suspended by adding a small amount of ethyl acetate, then was stirred overnight. Solid component were collected from the mixed solution by filtration and dried to obtain specified in the title compound (17 mg).

MS (ESI) m/z: 384 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C19H19ClN5O2384,12273; found: 384,12365.

1H-NMR (DMSO-d6) δ: 1,27-to 1.38 (2H, m), 1,46-of 1.55 (2H, m), 2,03-2,17 (1H, m), 3,19 of 3.28 (2H, m), with 3.79 (2H, d, J=7,4 Hz), 3,80-3,86 (2H, m), 7,74 (1H, d, J=2,9 Hz), of 7.97 (1H, d, J=1.7 Hz), 8,18 (1H, d, J=1.7 Hz), of 8.28 (1H, d, J=1.7 Hz), 8,65 (1H, d, J=2.3 Hz), 11,63 (1H, user. C)12,09 (1H, user. C).

(Example 36)

6-(4-Methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-3-iodine-4-methylpyridin-2-amine

5-Bromo-4-methylpyridin-2-amine (3.1 g) was dissolved in acetic acid (20 ml). Was added N-jodatime (3.8 g) and triperoxonane acid (0.2 ml) and the mixture was stirred at room temperature for 2.5 hours. The reaction solution was poured into ice water and neutralized 28% aqueous ammonia solution. Then on Ardenne solid substance was collected by filtration, washed with water and dried to obtain specified in the title compound (4.9 g).

MS (ESI) m/z: 313 (M+H)+.

1H-NMR (DMSO-d6) δ: 2,59 (3H, s), free 5.01 (1H, user. C)8,02 (1H, s).

Stage 2

5-Bromo-4-methyl-3-[(trimethylsilyl)ethinyl]methylpyridin-2-amine

The compound obtained in the above stage 1 (3.0 g)was dissolved in tetrahydrofuran (12 ml) was added triethylamine (60 ml) and copper iodide (0.04 g). The atmosphere was replaced with nitrogen atmosphere. Next was added trimethylsilylacetamide (1.1 g) and bis(triphenylphosphine)palladium(II) dichloride (0.1 g) and the mixture was stirred at room temperature overnight. The reaction solution was distributed between ethyl acetate and water and the organic layer was washed with saturated saline solution. The organic layer was dried and then concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (2.5 g).

MS (ESI) m/z: 283 (M+H)+.

1H-NMR (CDCl3) δ: 0,28 (9H, s), is 2.44 (3H, s), 4,99 (1H, user. C)of 8.04 (1H, s).

Stage 3

5-Bromo-4-methyl-1H-pyrrolo[2,3-b]pyridine

A solution of the compound obtained in the above stage 2 (14.0 g), N-organic (200 ml) was slowly added dropwise to a solution of tert-butoxide potassium (11.6 g) in N-organic (300 ml) at 80°C and then the mixture was stirred at 80°C within 30 minutes. The reaction solution was cooled to room temperature, diluted with ethyl acetate and washed with water. The organic layer was dried and then concentrated under reduced pressure. The precipitated solid was collected by filtration through a mixture of diethyl ether-hexane to obtain specified in the title compound (8.6 g).

MS (ESI) m/z: 211 (M+H)+.

1H-NMR (CDCl3) δ: 2,62 (3H, s), 6,50-is 6.54 (1H, m), 7,29-to 7.32 (1H, m), 8,35 (1H, s) 9,36 (1H, user. C).

Stage 4

tert-Butyl 5-bromo-4-methyl-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Specified in the title compound (339 mg) was obtained in a way similar to stage 1 of example 35 using the compound obtained in the above stage 3 (276 mg).

MS (ESI) m/z: 311 (M+H)+.

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), 2,58 (3H, s), 6,53 (1H, d, J=4.0 Hz), to 7.61 (1H, d, J=4.0 Hz), charged 8.52 (1H, s).

Stage 5

3-Cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (136 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (179 mg)and the compound obtained in the above stage 4 (126 mg).

MS (ESI) m/z: 444 (M+H)+.

Stage 6

6-(4-Methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The decree of the TES in the title compound (54 mg) was obtained by way similar to the stage 6 of example 35 using the compound obtained in the above stage 5 (136 mg).

MS (ESI) m/z: 364 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C20H22N5O2364,17735; found: 364,17525.

1H-NMR (DMSO-d6) δ: 1,27-1,32 (2H, m), 1,50 (2H, d, J=11.5 Hz), 2,03-2,05 (1H, m), 2,47 (3H, s), 3,21-3,24 (2H, m), 3,70 of 3.75 (2H, m), 3,79-a-3.84 (2H, m), 6,56 return of 6.58 (1H, m), 7,47-7,49 (1H, m), 7,63 (1H, s), to $ 7.91 (1H, d, J=the 1.7 Hz), 8,10 (1H, s), are 11.62 (1H, user. C)11,66 (1H, user. C).

(Example 37)

6-(3-Methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-[3-Cyclohex-1-EN-1-yl-2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-2H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde

Specified in the title compound (173 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (296 mg)and 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde obtained by the method described in WO 2004/101565 (159 mg).

MS (ESI) m/z: 458 (M+H)+.

1H-NMR (CDCl3) δ: 1,26-of 1.41 (2H, m), 1,48-of 1.57 (2H, m), 1,62-1,71 (2H, m), 1,73-to 1.82 (2H, m), 2.05 is-to 2.18 (1H, m), 2,20-of 2.28 (2H, m), 2,36 is 2.44 (2H, m), 3,19-3,29 (2H, m), 3,79-3,88 (4H, m), 5,94-6,00 (1H, m), to 7.77-7,83 (1H, m,), of 8.04 (1H, d, J=2.3 Hz), 8,29 (1H, d, J=2.3 Hz), 8,55 (1H, s), 8,63 (1H, d, J=2.3 Hz), 8,69 (1H, d, J=2.3 Hz), becomes 9.97 (1H, s).

Stage 2

3-Cyclohex-1-EN-1-yl-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetr the hydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above stage 1 (120 mg)was dissolved in methanol (4 ml). Added dimethylamine hydrochloride (43 mg) and sodium acetate (34 mg) and the mixture was stirred at room temperature for 1.5 hours. Additionally added cyanoborohydride sodium (46 mg) and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate and washed with saturated saline solution. The organic layer was dried and then concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (50 mg).

MS (ESI) m/z: 444 (M+H)+.

1H-NMR (CDCl3) δ: 1,46-of 1.56 (2H, m), of 1.65 (2H, d, J=13,2 Hz), 1,75-1,80 (2H, m), 1,88-of 1.93 (2H, m), 2,15-2,22 (1H, m), 2,33-of 2.36 (2H, m), 2,39 (3H, d, J=1.1 Hz), 2,49-2,52 (2H, m), 3,35-3,39 (2H, m), 3,85 (2H, d, J=6,9 Hz), 3,97-4,01 (2H, m), between 6.08 and 6,09 (1H, m), 7,17-to 7.18 (1H, m), 7,38 (1H, d, J=1.7 Hz), 8,00 (1H, d, J=2.3 Hz), 8,30 (1H, d, J=2.3 Hz), of 8.47 (1H, d, J=2.3 Hz), 9,36 (1H, s).

Stage 3

6-(3-Methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (26 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (50 mg).

MS (ESI) m/z: 364 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H22N5O2364,17735 found: 364,17567.

1H-NMR (DMSO-d6) δ: 1,27-of 1.35 (2H, m), 1,47-is 1.51 (2H, m), 2,07-2,11 (1H, m), 2,31 (3H, s), 3,23 (2H, t, J=10,9 Hz), of 3.77 (2H, d, J=7,4 Hz), 3,79-a 3.83 (2H, m), 7,27 (1H, s), of 7.90 (1H, d, J=1.7 Hz), 8,17 (1H, d, J=1.7 Hz), 8,24 (1H, d, J=1.7 Hz), 8,49-8,51 (1H, m), 11,37 (1H, s), 11,58 (1H, s).

(Example 38)

1-(1,4-Dioxane-2-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-(1,4-dioxane-2-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (312 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg), and 1,4-dioxane-2-ylmethanol obtained by the method described in Bioorg. Med. Chem. 15, 2667-2679 (2007) (135 mg).

MS (APCI) m/z: 394 [M+H]+.

1H-NMR (CDCl3) δ: at 1.73 to 1.76 (2H, m), 1,84-of 1.88 (2H, m), 2,30-2,31 (2H, m), 2,41 is 2.43 (2H, m), 3,35-3,93 (9H, m), of 6.02 (1H, m), 7,49 (1H, d, J=2.3 Hz), of 8.09 (1H, d, J=2.3 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-(1,4-dioxane-2-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (47 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (122 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (83 mg).

MS (APCI) m/z: 432 [M+H]+.

Stage 3

1-(1,4-Dioxane-2-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyrid is n-2-he

Specified in the title compound (32 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (47 mg).

HRMS (ESI) [M+H]+calculated: C18H17N5O3352,14096; found: 352,14017.

1H-NMR (DMSO-d6) δ: 3,29-4,01 (9H, m), 6,51-of 6.52 (1H, m), 7,52-rate of 7.54 (1H, m), 7,84-a 7.85 (1H, m), by 8.22-of 8.25 (2H, m), 8,53 (1H, d, J=2.3 Hz), are 11.62 (1H, s), 11,74 (1H, s).

(Example 39)

1-[(2R)-1,4-Dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(2R)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (602 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (300 mg)and (2R)-1,4-dioxane-2-ylmethanol obtained by the method described in Bioorg. Med. Chem. 15, 2667-2679 (2007) (169 mg).

MS (ESI) m/z: 394 (M+H)+.

1H-NMR (CDCl3) δ: at 1.73 to 1.76 (2H, m), 1,84-of 1.88 (2H, m), 2,30-2,31 (2H, m), 2,41 is 2.43 (2H, m), 3,37 (1H, m), 3,56-of 3.60 (1H, m), 3,66-to 3.73 (2H, m), 3,78-a 3.83 (2H, m), 3,86-of 3.94 (3H, m), 6,00-6,03 (1H, m), 7,49 (1H, d, J=2,3 Hz), of 8.09 (1H, d, J=2.3 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2R)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (91 mg) was obtained in a way similar to stage 3 of example 1, using the the group obtained in the above stage 1 (180 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (69 mg).

MS (ESI) m/z: 432 (M+H)+.

1H-NMR (CDCl3) δ: 1,75-1,80 (2H, m), 1,88-of 1.93 (2H, m), 2,32-of 2.36 (2H, m), 2,49-2,52 (2H, m), 3,41 is-3.45 (1H, m), 3,57-of 3.60 (1H, m), 3,68-3,74 (2H, m), of 3.77-of 3.80 (1H, m), 3,90-was 4.02 (4H, m), between 6.08 and 6,09 (1H, m), 6,60 (1H, DD, J=3,4) and 1.7 Hz), 7,41 (1H, DD, J=3,4, and 2.3 Hz), 7,58 (1H, d, J=1.7 Hz), of 8.09 (1H, d, J=1.7 Hz), 8,30 (1H, d, J=2.3 Hz), and 8.50 (1H, d, J=1.7 Hz), 9,63 (1H, user. C).

Stage 3

1-[(2R)-1,4-Dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (31 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (91 mg).

MS (ESI) m/z: 352 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H18N5O3352,14096; found: 352,13790.

1H-NMR (DMSO-d6) δ: 3,29-4,01 (9H, m), 6,51-of 6.52 (1H, m), 7,52-rate of 7.54 (1H, m), 7,84-a 7.85 (1H, m), by 8.22-of 8.25 (2H, m), 8,53 (1H, d, J=2.3 Hz), are 11.62 (1H, s), 11,74 (1H, s).

(Example 40)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (593 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (300 mg)and (2S)-1,4-dio the San 2-ylmethanol, obtained by the method described in Bioorg. Med. Chem. 15, 2667-2679 (2007) (169 mg).

MS (ESI) m/z: 394 (M+H)+.

1H-NMR (CDCl3) δ: at 1.73 to 1.76 (2H, m), 1,84-of 1.88 (2H, m), 2,30-2,31 (2H, m), 2,41 is 2.43 (2H, m), 3,37 (1H, m), 3,56-of 3.60 (1H, m), 3,66-to 3.73 (2H, m), 3,78-a 3.83 (2H, m), 3,86-of 3.94 (3H, m), 6,00-6,03 (1H, m), 7,49 (1H, d, J=2,3 Hz), of 8.09 (1H, d, J=2.3 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (89 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (180 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (69 mg).

MS (ESI) m/z: 432 (M+H)+.

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (32 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (89 mg).

MS (ESI) m/z: 352 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H18N5O3352,14096; found: 352,14104.

1H-NMR (DMSO-d6) δ: 3,29-4,01 (9H, m), 6,51-of 6.52 (1H, m), 7,52-rate of 7.54 (1H, m), 7,84-a 7.85 (1H, m), by 8.22-of 8.25 (2H, m), 8,53 (1H, d, J=2.3 Hz), are 11.62 (1H, s), 11,74 (1H, s).

(Example 41)

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Article is Diya 1

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (240 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in stage 1 of example 40 (353 mg).

MS (ESI) m/z: 442 (M+H)+.

1H-NMR (CDCl3) δ: of 1.36 (12H, s), of 1.74 to 1.76 (2H, m), 1,86-1,89 (2H, m), 2,31 of-2.32 (2H, m), 2,43 at 2.45 (2H, m), of 3.43 (1H, DD, J=11,5, 9.6 Hz), 3,62 (1H, DD, J=11,5, 2.7 Hz), 3,68-3,70 (2H, m), 3,78-a 3.87 (2H, m), 3,89-are 3.90 (2H, m), 3,95-of 3.97 (1H, m), 6,01-6,03 (1H, m), to 7.61 (1H, d, J=1.2 Hz), to 8.45 (1H, d, J=1.2 Hz).

Stage 2

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)3-cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (122 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (240 mg)and the compound obtained in stage 1 of example 35 (198 mg).

MS (ESI) m/z: 466 (M+H)+.

Stage 3

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (54 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (122 mg).

MS (ESI) m/z: 386 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H17ClN5O3386,10199; found: 386,10009.

1H-NMR (DMSO-d6) δ: 3,33-was 4.02 (9H, m), 7,74-7,76 (1H, m), to $ 7.91 (1H, d, J=1.7 Hz), 8,18 (1H, d, J=1.7 Hz), 8,29 (1H, d, J=2.3 Hz), 8,64 (1H, d, J=2.3 Hz), 11,66 (1H, s), 12,10 (1H, user. C).

(Example 42)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (41 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (153 mg)and the compound obtained in stage 4 of example 36 (108 mg).

MS (ESI) m/z: 446 (M+H)+.

Stage 2

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (20 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (41 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N5O3366,15661; found: 366,15640.

1H-NMR (DMSO-d6) δ: 2,47 (3H, s), 3.33 and-3,95 (9H, m), 6,56 return of 6.58 (1H, m), 7,47-7,50 (1H, m), 7,56 (1H, s), 7,92-to 7.93 (1H, m), of 8.09 (1H, s), 11,64-11,67 (2H, m).

(Example 43)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

<> Stage 1

5-[3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-2-oxo-2,3-dihydro-2H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde

Specified in the title compound (41 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (190 mg)and 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde obtained by the method described in WO 2004/101565 (97 mg).

MS (ESI) m/z: 460 (M+H)+.

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (27 mg) was obtained in a way similar to step 2 of example 37, using the compound obtained in the above stage 1 (41 mg).

MS (ESI) m/z: 446 (M+H)+.

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (26 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (49 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N5O3366,15661; found: 366,15790.

1H-NMR (DMSO-d6) δ: 2,32 (3H, s), 3.33 and-4,04 (9H, m), 7,28 (1H, s), a 7.85 (1H, d, J=1.2 Hz), 8.17-a 8,18 (1H, m), compared to 8.26 (1H, d, J=1.2 Hz), 8,50-and 8.50 (1H, m), 11,38 (1H, user. C)to 11.61 (1H, user. C).

(Example 44)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-5-methyl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (0.64 g) was obtained in a way similar to step 2 of example 35 using the compound obtained in stage 2 of example 7 (1.0 g).

MS (ESI) m/z: 410 (M+H)+.

Stage 2

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 1 (640 mg)in tetrahydrofuran (20 ml) was added (2S)-1,4-dioxane-2-ylmethanol (319 mg) and triphenylphosphine (817 mg). After this dropwise at 0°C was added a solution of di-2-methoxyethyl of azodicarboxylate (730 mg) in tetrahydrofuran (5 ml) and the mixture was stirred for 11 hours while gradually warming to room temperature. The reaction solution was diluted with diethyl ether, washed with water and saturated saline solution in this order and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (480 mg).

MS (ESI) m/z: 308 (M+H)+.

1H-NMR (CDCl3) δ: 1,72 to 1.76 (2H,m), 1,83-of 1.88 (2H, m), 2,28 of-2.32 (2H, m), 2,43 is 2.46 (2H, m)2,60 (3H, s)to 3.36 (1H, DD, J=11,5, 9.7 Hz), 3,54-of 3.60 (1H, m), 3,66-3,71 (2H, m), of 3.77-3,81 (2H, m), 3,85-to 3.92 (3H, m), 5,99-6,01 (1H, m), 7,47 (1H, s).

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (180 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above step 2 (150 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (ESI) m/z: 446 (M+H)+.

1H-NMR (CDCl3) δ: 1,75-to 1.79 (2H, m), 1,87-of 1.93 (2H, m), 2,31 to 2.35 (2H, m), 2,48 (3H, s), 2,52 is 2.55 (2H, m), 3,39 (1H, DD, J=11,5, 9.7 Hz), 3,55 is 3.76 (4H, m), 3,83-of 3.95 (4H, m), 6,06-between 6.08 (1H, m), to 6.57 (1H, DD, J=3,7, 2.0 Hz), from 7.24 (1H, s), 7,39-7,39 (1H, m), 7,89 (1H, d, J=1.2 Hz), of 8.27 (1H, d, J=1.7 Hz), 8,97 (1H, s).

Stage 4

1-[(2S)-1,4-Dioxane-2-ylmethyl]-5-methyl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (75 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (180 mg).

MS (ESI) m/z: 366 (M+H)+.

1H-NMR (DMSO-d6) δ: of 2.38 (3H, s), 3,28-3,30 (1H, m), 3,40-to 3.52 (2H, m)and 3.59 (1H, d, J=10.5 Hz), 3,68-of 3.80 (3H, m), 3,82-3,93 (2H, m), of 6.49 (1H, DD, J=3,4, 1.7 Hz), 7,41 (1H, s), 7,53-7,53 (1H, m), 7,95 (1H, d, J=2.0 Hz), 8,21 (1H, d, J=2.2 Hz), 11,49 (1H, user. C)11,74 (1H, user. C).

(Example 45)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-5-methyl-6-(4-methyl-1H-pyrrole,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (433 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in stage 2 of example 44 (470 mg).

MS (ESI) m/z: 456 (M+H)+.

1H-NMR (CDCl3) δ: 1,36 (6H, s), was 1.58 (6H, s), 1,71 to 1.76 (2H, m), 1,83-of 1.88 (2H, m)of 1.93 (6H, s), 2,28-2,31 (2H, m), a 2.45-2.49 USD (2H, m), of 2.72 (3H, s), of 3.43 (1H, DD, J=12,0, 9.7 Hz), to 3.58-3,63 (1H, m), 3,67-and 3.72 (2H, m), 3,78-3,97 (5H, m), 4,07-4.09 to (2H, m), 6,00-of 6.02 (1H, m), 7,58 (1H, s).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (74 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (130 mg)and the compound obtained in stage 4 of example 36 (106 mg).

MS (ESI) m/z: 460 (M+H)+.

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-5-methyl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (13 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (70 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 2,15-of 2.15 (3H, m, 2,25-of 2.26 (3H, m), 3,39-3,51 (3H, m), 3,56-3,61 (1H, m), 3,67-3,91 (5H, m), 6,55-6,56 (1H, m), 7,29-7,30 (1H, m), 7,47-of 7.48 (1H, m), 7,95-of 7.97 (1H, m), 11,50-to 11.52 (1H, m), 11,64-11,66 (1H, m).

(Example 46)

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Stage 1

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (35 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 45 (130 mg)and the compound obtained in stage 1 of example 35 (113 mg).

MS (ESI) m/z: 480 (M+H)+.

Stage 2

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (17 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (35 mg).

MS (ESI) m/z: 400 (M+H)+.

1H-NMR (DMSO-d6) δ: of 2.38 (3H, s), 3.27 to and 3.31 (1H, m), 3,41-to 3.52 (2H, m)and 3.59 (1H, d, J=10,9 Hz), 3,68-of 3.80 (3H, m), 3,84-3,88 (1H, m), 3,89-of 3.94 (1H, m), 7,45 (1H, s), 7,76 (1H, d, J=2,9 Hz), of 7.90 (1H, d, J=1.7 Hz), 8,32 (1H, d, J=2.3 Hz), 11,53 (1H, s), 12,11 (1H, s).

(Example 47)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-5-methyl-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Stage 1

Specified in the title compound (385 mg) was obtained in a way similar to stage 1 of example 35, using 5-bromo-3-methyl-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2009/016460 (365 mg).

MS (ESI) m/z: 311 (M+H)+.

1H-NMR (CDCl3) δ: of 1.66 (9H, s)of 2.23 (3H, d, J=1.5 Hz), 7,41-7,41 (1H, m), 7,94 (1H, d, J=2.2 Hz), 8,51 (1H, d, J=2.2 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-5-methyl-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (105 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 45 (160 mg)and the compound obtained in the above stage 1 (100 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1,75-to 1.79 (2H, m), 1,87-of 1.92 (2H, m), 2,32-of 2.34 (2H, m), 2,35 (3H, d, J=1,15 Hz), 2,47 (3H, s), 2,52 is 2.55 (2H, m), 3,39 (1H, DD, J=11,5, 9.7 Hz), 3,55 (1H, TD, J=11,7, 2,9 Hz), 3,65-3,70 (2H, m), 3.72 points is 3.76 (1H, m), 3,84-of 3.94 (4H, m), 6,06-between 6.08 (1H, m), 7,14 (1H, s), 7,24 (1H, s), 7,81 (1H, d, J=2.3 Hz), 8,24 (1H, d, J=2.3 Hz), 8,59 (1H, user. C).

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-5-methyl-6-(3-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-he

Specified in the title compound (42 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (103 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 2,28 (3H), of 2.38 (3H, s), 3.27 to and 3.31 (1H, m), 3,40-to 3.52 (2H, m)and 3.59 (1H, d, J=10,9 Hz), 3,68-3,93 (5H, m), 7,29 (1H, s), 7,41 (1H, s), 7,89 (1H, d, J=2.3 Hz), 8,18 (1H, d, J=1.7 Hz), is 11.39 (1H, s), 11,49 (1H, s).

(Example 48)

1-[2-(3,6-Dihydro-2H-Piran-4-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Ethyl tetrahydro-4H-Piran-4-evidencethat

Ethyl 3,6-dihydro-2H-Piran-4-ylacetic

In dimethoxyethane (150 ml) was added 55% sodium hydride (2.6 g). Within five minutes dropwise in a nitrogen atmosphere under ice cooling was added ethyldichlorosilane (9.6 ml) and the mixture was stirred at the same temperature for 45 minutes. Was added dropwise a solution of tetrahydro-4H-Piran-4-it (4.0 g) in dimethoxyethane (10 ml) for five minutes. The mixture was stirred at room temperature for 10 minutes and then heated under reflux for one hour. The reaction solution was poured into water, then extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the title compounds, elitetrader-4H-Piran-4-evidencethat (1.7 g) and ethyl 3,6-dihydro-2H-Piran-4-ilaclama (2.2 g), both as colourless oils.

Ethyl tetrahedron-Piran-4-evidencethat

1H-NMR (CDCl3) δ: of 1.28 (3H, t, J=7,1 Hz), is 2.30 to 2.35 (2H, m), 2,98-3,03 (2H, m), 3,74 (2H, t, J=5.6 Hz), of 3.77 (2H, t, J=5.6 Hz), of 4.16 (2H, q, J=7,1 Hz), of 5.68 (1H, s).

Ethyl 3,6-dihydro-2H-Piran-4-ylacetic

1H-NMR (CDCl3) δ: of 1.27 (3H, t, J=7,1 Hz), 2,12-2,19 (2H, m), 3,01 (2H, s), 3,80 (2H, t, J=5.5 Hz), 4,11-4,19 (4H, m), 5,58-5,62 (1H, m).

Stage 2

2-(3,6-Dihydro-2H-Piran-4-yl)ethanol

Specified in the title compound (1.6 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33, using ethyl 3,6-dihydro-2H-Piran-4-ylacetic obtained in the above stage 1.

1H-NMR (CDCl3) δ: 1.55V (1H, user. s), 2.06 to a 2.12 (2H, m), 2,28 (2H, t, J=6.2 Hz), and 3.72 (2H, t, J=6.3 Hz), 3,80 (2H, t, J=5.5 Hz), 4,11-to 4.15 (2H, m), of 5.53-to 5.57 (1H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-[2-(3,6-dihydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (705 mg) was obtained as a mixture by the method similar to those used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg)and the compound obtained in the above stage 2 (146 mg).

1H-NMR (CDCl3) δ: 1.70 to of 1.78 (2H, m), 1,81-1,90 (2H, m), 2,11-to 2.18 (2H, m), 2.26 and is 2.33 (2H, m), 2,36 at 2.45 (4H, m), of 3.78 (2H, t, J=5.5 Hz), of 3.97 (2H, t, J=7.2 Hz), 4,00-Android 4.04 (2H, m), lower than the 5.37 (1H, s), 5,96-6,00 (1H, m), 7,30 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=2.0 Hz).

Stage 4

6-Bromo-1-[2-(3,6-dihydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (192 mg) was obtained is a colourless powder method similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (705 mg).

1H-NMR (CDCl3) δ: 2,13-2,19 (2H, m), 2,42 (2H, t, J=7.0 Hz), of 3.78 (2H, t, J=5.4 Hz), of 3.95 (2H, t, J=7,3 Hz), was 4.02-4,06 (2H, m), 5,39-5,43 (1H, m), 7,31 (1H, d, J=1,8 Hz), 8,10 (1H, d, J=1,8 Hz), of 8.95 (1H, user. C).

Stage 5

1-[2-(3,6-Dihydro-2H-Piran-4-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (55 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (100 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (90 mg).

MS (ESI) m/z: 362 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H19N5O2362,16170; found: 362,16021.

1H-NMR (DMSO-d6) δ: 2,07-and 2.14 (2H, m), a 2.36-to 2.42 (2H, m), 3,63 (2H, t, J=5.7 Hz), 3,86-are 3.90 (2H, m)to 3.99 (2H, t, J=6.6 Hz), 5,35 is 5.38 (1H, m), of 6.49-of 6.52 (1H, m), 7,51-rate of 7.54 (1H, m), 7,86 (1H, d, J=1.2 Hz), by 8.22 compared to 8.26 (2H, m,), 8,55 (1H, d, J=2.0 Hz), to 11.56 (1H, user. C)11,72 (1H, user. C).

(Example 49)

1-[2-(3,6-Dihydro-2H-Piran-4-yl)ethyl]-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (42 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 48 (92 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (33 mg).

MS (ESI) m/z: 361 (M+H)+

HRMS (ESI) [M+H]+calculated: C20H20N4O2361,16645; found: 361,16597.

1H-NMR (DMSO-d6) δ: 2,07-and 2.14 (2H, m), 2,35-to 2.41 (2H, m), 3,63 (2H, t, J=5.4 Hz), 3,85-are 3.90 (2H, m)to 3.99 (2H, t, J=7.0 Hz), 5,34 is 5.38 (1H, m), 6,47-6,50 (1H, m), 7,37-7,44 (2H, m), of 7.48 (1H, d, J=8.5 Hz), 7,76 for 7.78 (1H, m,), 7,84-7,86 (1H, m), 8,19 (1H, d, J=1.7 Hz), 11,14 (1H, user. C)11,49 (1H, user. C).

(Example 50)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-[2-(tetrahydro-2H-Piran-4-yl)propyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Ethyl 2-(tetrahydro-2H-Piran-4-yl)propanoate

Diisopropylamine (2.8 g) was dissolved in tetrahydrofuran (20 ml). Dropwise in a nitrogen atmosphere under ice cooling was added a solution of n-utility in hexane (2,64 N., 11 ml) and the mixture was stirred at the same temperature for 15 minutes. The reaction solution was cooled to -78°C. was added dropwise a solution of ethyl 2-(tetrahydro-2H-Piran-4-yl)acetate (4.0 g) in tetrahydrofuran (15 ml) and the mixture was stirred at the same temperature for 15 minutes. Then was added dropwise methyliodide (2.2 ml). The mixture was stirred at the same temperature for 10 minutes and then heated to room temperature and was stirred for 3 hours. Under ice cooling was added 1 N. aqueous solution of hydrochloric acid, then was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium bicarbonate and saturated solely the solution and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (4.0 g) as a colourless oil.

1H-NMR (CDCl3) δ: of 1.13 (3H, d, J=6,8 Hz)of 1.26 (3H, t, J=7.2 Hz), 1.30 and a 1.46 (2H, m), 1,47-of 1.55 (1H, m), 1,58-of 1.66 (1H, m), 1,72-of 1.84 (1H, m), 2.21 are of 2.30 (1H, m), 3,37 (2H, TT, J=11,8, 2,9 Hz), 3,92-a 4.03 (2H, m), 4,14 (2H, kV, J=7,2 Hz).

Stage 2

2-(Tetrahydro-2H-Piran-4-yl)propan-1-ol

Specified in the title compound (1.4 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained in the above stage 1 (1.8 g).

1H-NMR (CDCl3) δ: of 0.93 (3H, d, J=6.8 Hz), 1,20-1,72 (7H, m), 3.33 and is-3.45 (2H, m), 3,49-to 3.58 (1H, m), 3,59 at 3.69 (1H, m), 3.95 to 4,07 (2H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-[2-(tetrahydro-2H-Piran-4-yl)propyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (255 mg) was obtained as a mixture by the method similar to those used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and the compound obtained in the above stage 2 (147 mg).

1H-NMR (CDCl3) δ: of 0.91 (3H, d, J=6.8 Hz), 1,43 is 1.60 (3H, m), 1,63-of 1.78 (4H, m), 1,81-1,90 (2H, m), 1,90-to 1.98 (1H, m), 2.26 and-of 2.34 (2H, m), 2,36 is 2.44 (2H, m), 3,31-of 3.42 (2H, m), 3,63 (1H, DD, J=14,1, a 8.9 Hz), with 3.89 (1H, DD, J=14,1, 6,1 Hz), 3.96 points-4,06 (2H, m), 5,97-6,03 (1H, m), 7,25 (1H, d, J=2.0 Hz), 8,10 (1H, d, J=2.0 Hz).

Stage 4

6-Bromo-1-[2-(tetrahydro-2H-Piran-4-yl)propyl]-1,3-di is Idro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (73 mg) was obtained as a colourless solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (255 mg).

1H-NMR (CDCl3) δ: from 0.90 (3H, d, J=6.8 Hz), 1,48-to 1.59 (3H, m), 1,63 is 1.70 (1H, m), 1,88 of 1.99 (2H, m), 3.33 and-of 3.42 (3H, m), 3,63 (1H, DD, J=14,0, a 8.9 Hz), 3,85 (1H, DD, J=13.3-inch and 5.7 Hz), 3,97-4,07 (2H, m), 7.23 percent-7,26 (1H, m), 8,06-8,09 (1H, m).

Stage 5

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-[2-(tetrahydro-2H-Piran-4-yl)propyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (45 mg) was obtained as a colourless solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (73 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (63 mg).

MS (ESI) m/z: 378 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H23N5O2378,19300; found: 378,19239.

1H-NMR (DMSO-d6) δ: 0,81 (3H, d, J=6.6 Hz), 1,22 is 1.58 (4H, m), 1,61 is 1.70 (1H, m), 1,94-2,05 (1H, m), 3,19-3,30 (2H, m), 3,66 is 3.76 (1H, m), 3,82-of 3.94 (3H, m), 6,50-6,53 (1H, m), 7,50-rate of 7.54 (1H, m), 7,81 (1H, s), by 8.22-of 8.25 (2H, m), 8,53 (1H, d, J=1.7 Hz), 11,60 (1H, user. C)11,73 (1H, user. C).

(Example 51)

1-[2-fluoro-2-(tetrahydro-2H-Piran-4-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Ethyl fluoride(tetrahydro-2H-Piran-4-yl)acetate

Ethyl 2-(tetrahydro-mpirun-4-yl)acetate (2.0 g) was dissolved in tetrahydrofuran (20 ml). A solution of bis(trimethylsilyl)amide lithium in tetrahydrofuran (1,0 M, 17 ml) was added dropwise in a nitrogen atmosphere under ice cooling and the mixture was stirred at the same temperature for 15 minutes. Then the solution was added N-forbindelseshastighed (7,3 g) in tetrahydrofuran (20 ml) and the mixture was stirred at the same temperature for 3 hours. Under ice cooling was added a saturated aqueous solution of ammonium chloride and water, then was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. To the residue was added a mixture of chloroform-diethyl ether and the insoluble substance was removed by filtration. After that, the solvent was evaporated and the residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane and chloroform) to obtain specified in the header compounds containing insoluble substance (0.9 g) as a pale orange oil.

MS (ESI) m/z: 191 (M+H)+.

Stage 2

2-Fluoro(tetrahydro-2H-Piran-4-yl)ethanol

Specified in the title compound (0.4 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained in the above stage 1 (0.9 g).

1H-NMR (CDCl3) δ: 1,42-of 1.66 (3H, m), 1,74-2,05 (3H, m), 3,35-3,44 (2H, m), 3,68-3,88 (2H, m), 3.95 to 4,0 (2H, m), 4,21-4,28 (0,5H, m), 4,34-4,39 (0,5H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-[2-fluoro-2-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (196 mg) was obtained as a mixture by the method similar to those used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and the compound obtained in the above stage 2 (151 mg).

1H-NMR (CDCl3) δ: 1,48-to 1.61 (2H, m), 1.70 to 1,95 (7H, m), 2,28-of 2.34 (2H, m), 2,39 is 2.44 (2H, m), 3,35 is-3.45 (2H, m), 3,92-4,06 (3H, m), 4,17 (1H, DDD, J=29,4, 15,2, 2.2 Hz), 4,49 (0,5H, TD, J=7,2, 2.2 Hz), br4.61 (0,5H, TD, J=7,2 and 2.2 Hz), 5,99-6,03 (1H, m), 7,43 was 7.45 (1H, m), 8,11 (1H, d, J=2.0 Hz).

Stage 4

6-Bromo-1-[2-fluoro-2-(tetrahydro-2H-Piran-4-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (145 mg) was obtained as a pale yellow amorphous substance in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (196 mg).

1H-NMR (CDCl3CD3OD (10:1)) δ: of 1.23 to 1.34 (2H, m), 1,49-of 1.62 (2H, m), 1.70 to a 1.96 (2H, m), 3,35-3,47 (2H, m), 3,91-4,19 (4H, m), 4,42-4,50 (0,5H, m), 4.53-in-4,62 (0,5H, m), 7,30 (1H, d, J=2.0 Hz), to 7.93 (1H, d, J=2.0 Hz).

Stage 5

1-[2-fluoro-2-(tetrahydro-2H-Piran-4-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (27 mg) was obtained as a colourless solid in a way similar to stage 3 of example , using the compound obtained in the above stage 4 (71 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (60 mg).

MS (ESI) m/z: 382 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H20FN5O2382,16793; found: 382,16778.

1H-NMR (DMSO-d6) δ: 0,81 (3H, d, J=6.6 Hz), 1,22 is 1.58 (4H, m), 1,61 is 1.70 (1H, m), 1,94-2,05 (1H, m), 3,19-3,30 (2H, m), 3,66 is 3.76 (1H, m), 3,82-of 3.94 (3H, m), 6,50-6,53 (1H, m), 7,50-rate of 7.54 (1H, m), 7,81 (1H, s), by 8.22-of 8.25 (2H, m), 8,53 (1H, d, J=1.7 Hz), 11,60 (1H, user. C)11,73 (1H, user. C).

(Example 52)

1-{2-[CIS-2,6-Dimethylmorpholine-4-yl]ethyl}-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Ethyl [CIS-2,6-dimethylmorpholine-4-yl]acetate

CIS-2,6-Dimethylmorpholine (2.0 g) was dissolved in acetonitrile (70 ml). Added ethylbromoacetate (2.5 ml) and potassium carbonate (3.1 g) and the mixture was heated with stirring at 60°C for 12 hours. The solvent was evaporated and then the residue was added ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (2.9 g) as a colourless oil.

1H-NMR (CDCl3) δ: of 1.16 (6H, d, J=6,1 Hz)of 1.28 (3H, t, J=7,1 Hz)of 1.93 (2H, t, J=10,6 Hz), was 2.76-and 2.83 (2H, m), 3,18 (2H, s), 3,71-3,81 (2H, m), 4,19 (2H, q, J=7,1 Hz).

With the adiya 2

2-[CIS-2,6-Dimethylmorpholine-4-yl]ethanol

Specified in the title compound (2.3 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained in the above stage 1 (2.9 g).

1H-NMR (CDCl3) δ: of 1.16 (6H, d, J=6.3 Hz), 1,80-of 1.88 (2H, m), 2,52 (2H, t, J=5.5 Hz), 2,70 was 2.76 (2H, m), 2,71 (1H, user. C)3,62 (2H, t, J=5.5 Hz), 3,63-and 3.72 (2H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-{2-[CIS-2,6-dimethylmorpholine-4-yl]ethyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (248 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg)and the compound obtained in the above stage 2 (182 mg).

1H-NMR (CDCl3) δ: to 1.15 (6H, d, J=6.3 Hz), 1.70 to at 1.91 (6H, m), 2,27-of 2.34 (2H, m), 2,37 is 2.44 (2H, m)of 2.64 (2H, t, J=6.5 Hz), 2,77 (2H, d, J=10.5 Hz), 3,55-the 3.65 (2H, m), of 3.96 (2H, t, J=6.5 Hz), 5,97-of 6.02 (1H, m), 7,37 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz).

Stage 4

6-Bromo-1-{2-[CIS-2,6-dimethylmorpholine-4-yl]ethyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (165 mg) was obtained as a colorless amorphous substance in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (249 mg).

1H-NMR (CDCl3) δ: of 1.16 (6H, d, J=6.3 Hz), of 1.85 (2H, t, J=10,6 Hz)to 2.67 (2H, t, J=6.3 Hz), 2,82 (2H, d, J=10.5 Hz), to 3.58-3,68 (2H, m), of 3.97 (2H, t, J=6.3 Hz), 7,39 (1H, d, J1,8 Hz), 8,08 (1H, d, J=1,8 Hz), 10,53 (1H, user. C).

Stage 5

1-{2-[CIS-2,6-Dimethylmorpholine-4-yl]ethyl}-6-(1H-indol-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (33 mg) was obtained as a colourless solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (100 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (96 mg).

MS (ESI) m/z: 392 (M+H)+.

HRMS (ESI) [M+H]+calculated: C22H25N5O2392,20865; found: 392,20833.

1H-NMR (CDCl3) δ: to 1.15 (6H, d, J=6,1 Hz), of 1.85 (3H, t, J=10,7 Hz), of 2.72 (2H, t, J=6.6 Hz), 2,86 (2H, d, J=10.5 Hz), 3,60-3,71 (2H, m)4,06 (2H, t, J=6.6 Hz), 6,60-only 6.64 (1H, m), 7,29 (1H, t, J=2.7 Hz), 7,35-7,40 (1H, m,), 7,45-7,51 (2H, m), 7,79 (1H, d, J=1.2 Hz), 8,30 (1H, d, J=1.2 Hz), 8,39 (1H, user. C).

(Example 53)

1-{2-[CIS-2,6-Dimethylmorpholine-4-yl]ethyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (53 mg) was obtained as a colourless solid in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 52 (65 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (54 mg).

MS (ESI) m/z: 393 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H24N6O2393,20390; found: 393,20452.

1H-NMR (DMSO-d6) δ: of 1.02 (6H, d, J=6.3 Hz), 1,66 (2, t, J=10.5 Hz), 2,60 (2H, t, J=6,1 Hz), is 2.88 (2H, d, J=11,0 Hz), 3,38-3,47 (2H, m), 3.96 points-a 4.03 (2H, m), 6,48-of 6.52 (1H, m), 7,51-of 7.55 (1H, m), 7,86 (1H, s), 8,23 compared to 8.26 (2H, m), 8,54 (1H, d, J=1.5 Hz), to 11.56 (1H, user. C)11,73 (1H, user. C).

(Example 54)

1-{2-[(3S)-3-Methylmorpholin-4-yl]ethyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Ethyl [(3S)-3-methylmorpholin-4-yl]acetate

Specified in the title compound (1.6 g) was obtained as colorless oil by the method similar to those used in stage 1 of example 52, using (3S)-3-methylmorpholine (1.0 g).

1H-NMR (CDCl3) δ: 0,98 (3H, d, J=6.3 Hz), of 1.28 (3H, t, J=7,1 Hz), 2,65-to 2.74 (2H, m), 2,77 (1H, dt, J=11,7, 2.2 Hz), 3,23-of 3.27 (1H, m), with 3.27 (1H, d, J=16,3 Hz), 3,43 (1H, d, J=16,3 Hz), 3,64-and 3.72 (2H, m), of 3.77-a 3.83 (1H, m), 4,19 (2H, q, J=7.2 Hz).

Stage 2

2-[(3S)-3-Methylmorpholin-4-yl]ethanol

Specified in the title compound (1.3 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained in the above stage 1 (1.6 g).

1H-NMR (CDCl3) δ: 1,00 (3H, d, J=6,1 Hz), 2,25-of 2.38 (2H, m), 2.49 USD at 2.59 (1H, m), 2,73 (1H, user. C), 2,78-to 2.85 (1H, m), 2,93-to 3.02 (1H, m), or 3.28 (1H, DD, J=11,1, 8,4 Hz), 3,49-to 3.58 (1H, m), 3,61-to 3.73 (3H, m), 3.75 to 3,82 (1H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-{2-[(3S)-3-methylmorpholin-4-yl]ethyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (443 mg) was obtained in a way similar to stage 3 of example 35, use the I connection obtained in stage 2 of example 35 (400 mg)and the compound obtained in the above stage 2 (296 mg).

1H-NMR (CDCl3) δ: of 0.85 (3H, d, J=6.3 Hz), 1,71-of 1.78 (2H, m), 1,83-1,90 (2H, m), 2,27-of 2.34 (2H, m), 2,37-of 2.54 (5H, m), 2,85 (1H, dt, J=11,5, 2,9 Hz), 3,01-and 3.16 (2H, m), 3,55-of 3.64 (2H, m), of 3.78 (1H, dt, J=11,0, 2.7 Hz), a 3.87-3,98 (2H, m), 5,97-of 6.02 (1H, m), 7,38 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz).

Stage 4

6-Bromo-1-{2-[(3S)-3-methylmorpholin-4-yl]ethyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (364 mg) was obtained as a pale yellow amorphous substance in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (443 mg).

1H-NMR (CDCl3) δ: from 0.84 (3H, d, J=6.3 Hz), 2,39-2,52 (3H, m), 2.77-to of 2.86 (1H, m), 2.95 and-is 3.08 (1H, m), is 3.08-3,17 (1H, m), 3,53-of 3.64 (2H, m), 3,71-of 3.80 (1H, m), 3,81-of 3.94 (2H, m), 7,34-7,41 (1H, m), 8,01-8,08 (1H, m).

Stage 5

1-{2-[(3S)-3-Methylmorpholin-4-yl]ethyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (78 mg) was obtained as a colourless solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (147 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (126 mg).

MS (ESI) m/z: 379 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H22N6O2379,18825; found: 379,18744.

1H-NMR (DMSO-d6) δ: 0.75 in (3H, d, J=6,1 Hz), 2,27-2,47 (2, m), 2,87-2,96 (2H, m), 3,02-of 3.12 (1H, m), 3,34-of 3.42 (1H, m), 3,49 (2H, DD, J=11,0, 2,8 Hz), 3,61-3,68 (1H, m), 3,86-of 3.96 (1H, m), 3,97-4,08 (1H, m), of 6.49-6,53 (1H, m), 7,53 (1H, t, J=2,9 Hz), 7,86-7,88 (1H, m), by 8.22-of 8.25 (2H, m), 8,54 (1H, d, J=2.0 Hz), to 11.56 (1H, user. C)11,73 (1H, user. C).

(Example 55)

1-(2-Morpholine-4-retil)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-(2-morpholine-4-retil)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (340 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (300 mg), and N-(2-hydroxyethyl)morpholine (201 mg).

1H-NMR (CDCl3) δ: 1,71-of 1.78 (2H, m), 1,83-1,90 (2H, m), 2,27-of 2.34 (2H, m), 2,39 at 2.45 (2H, m), of 2.53 (4H, t, J=4.6 Hz), 2,68 (2H, t, J=6.4 Hz), to 3.67 (4H, t, J=4.6 Hz), of 3.97 (2H, t, J=6.4 Hz), 5,99-of 6.02 (1H, m), 7,39 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-(2-morpholine-4-retil)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (308 mg) was obtained as a pale yellow amorphous substance in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (325 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (234 mg).

1H-NMR (CDCl3) δ: 1,74-to 1.82 (2H, m), 1,86-of 1.95 (2H, m), 2,31-of 2.38 (2H, m), 2,47 of $ 2.53 (2H, m), 2,53 at 2.59 (4H, m)of 2.75 (2H, t, J=6.6 Hz), 3,65-3,70 (4H, m), 4,08 2H, t, J=6.6 Hz), 6,05-6,09 (1H, m), 6,59 (1H, DD, J=3,7, 2.0 Hz), 7,38-7,41 (1H, m), the 7.43 (1H, d, J=2.0 Hz), 8,07 (1H, d, J=1.7 Hz), of 8.28 (1H, d, J=2.0 Hz), 8,49 (1H, d, J=2.2 Hz), which is 9.09 (1H, s).

Stage 3

1-(2-Morpholine-4-retil)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (143 mg) was obtained as a colourless solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (308 mg).

MS (ESI) m/z: 365 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N6O2365,17260; found: 365,17207.

1H-NMR (DMSO-d6) δ: 2,44-2,49 (4H, m), 2.63 in (2H, t, J=6.3 Hz), 3,48-of 3.53 (4H, m)4,00 (2H, t, J=6.2 Hz), 6,51 (1H, d, J=3,4 Hz), 7,51-rate of 7.54 (1H, m), 7,87 (1H, s), by 8.22-of 8.25 (2H, m), 8,54 (1H, d, J=2.0 Hz), 11,57 (1H, user. C)11,73 (1H, user. C).

(Example 56)

1-[(1-Methylpiperidin-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(1-methylpiperidin-4-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (126 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg), and (1 methylpiperidin-4-yl)methanol (132 mg).

1H-NMR (CDCl3) δ: 1,36 of 1.50 (2H, m), 1,63 is 1.96 (9H, m), 2.26 and-of 2.34 (2H, m), and 2.27 (3H, s), 2,38 is 2.44 (2H, m), 2,82-2,90 (2H, m), of 3.73 (2H, d, J=7,1 Hz), 5,97-6,03 (1H, m), 7,25-7,28 (1H, m), 8,08 1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(1-methylpiperidin-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (132 mg) was obtained as a pale yellow amorphous substance in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (126 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (91 mg).

1H-NMR (CDCl3) δ: 1,40-of 1.55 (2H, m), 1,69-of 1.81 (4H, m), 1,84-of 1.95 (6H, m), of 2.25 (3H, s), 2,29-of 2.38 (2H, m), 2,45-2,52 (2H, m), 2,80-2,89 (2H, m), 3,83 (2H, d, J=6.8 Hz), 6,04-6,09 (1H, m), 6,57-of 6.61 (1H, m), 7,35 (1H, d, J=1.7 Hz), of 7.36-7,40 (1H, m), of 8.06 (1H, d, J=2.1 Hz), of 8.28 (1H, d, J=2.1 Hz), 8,49 (1H, d, J=2.1 Hz), 8,91 (1H, user. C).

Stage 3

1-[(1-Methylpiperidin-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (50 mg) was obtained as a colourless solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (132 mg).

MS (ESI) m/z: 363 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H22N6O 363,19333; found: 363,19277.

1H-NMR (DMSO-d6) δ: 1,22-of 1.39 (2H, m), 1,52-of 1.62 (2H, m), 1,75 is 1.91 (3H, m), of 2.15 (3H, s), 2,77 (2H, d, J=10.0 Hz), 3,76 (2H, d, J=7,1 Hz), of 6.49-is 6.54 (1H, m), 7,51-of 7.55 (1H, m), 7,87-to $ 7.91 (1H, m), by 8.22 compared to 8.26 (2H, m), 8,53-8,56 (1H, m), 11,58 (1H, user. C)11,73 (1H, user. C).

(Example 57)

1-[2-Piperazine-1-ileti]-6-(1H-p is Rolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

1-[2-(4-Acetylpiperidine-1-yl)ethyl]-6-bromo-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (174 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and 2-(4-acetylpiperidine-1-yl)ethanol (176 mg).

1H-NMR (CDCl3) δ: 1.70 to of 1.78 (2H, m), 1,82-1,90 (2H, m), of 2.08 (3H, s), 2,27-of 2.34 (2H, m), 2,37 is 2.44 (2H, m), 2.49 USD (2H, t, J=4.9 Hz), 2,53 (2H, t, J=4.9 Hz), 2,70 (2H, t, J=6.3 Hz), to 3.41 (2H, t, J=5.0 Hz), of 3.57 (2H, t, J=5.0 Hz), 3,98 (2H, t, J=6.3 Hz), 5,98-of 6.02 (1H, m), 7,35 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=2.0 Hz).

Stage 2

1-[2-(4-Acetylpiperidine-1-yl)ethyl]-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (156 mg) was obtained as a pale yellow amorphous substance in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (174 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (114 mg).

1H-NMR (CDCl3) δ: 1,73-to 1.82 (2H, m), 1,82-of 1.94 (2H, m)2,07 (3H, s), 2,30-of 2.38 (2H, m), 2,45-2,60 (6H, m), 2,77 (2H, t, J=6.5 Hz), 3,42 (2H, t, J=4,9 Hz)to 3.58 (2H, t, J=4.9 Hz), 4.09 to (2H, t, J=6.5 Hz), 6,04-6,10 (1H, m), 6,59 (1H, DD, J=3,5, 1.8 Hz), 7,40-7,44 (2H, m), 8,08 (1H, d, J=2.0 Hz), 8,30 (1H, d, J=2.0 Hz), and 8.50 (1H, d, J=2.0 Hz), 10,04 (1H, user. C).

Stage 3

1-[2-Piperazine-1-ileti]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]feast the DIN-2-he

Specified in the title compound (34 mg) was obtained as a colourless solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (156 mg).

MS (ESI) m/z: 364 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H23N7O2364,18858; found: 364,18800.

1H-NMR (DMSO-d6) δ: 2,34-of 2.45 (4H, m), 2,55-to 2.67 (6H, m), 3,93-was 4.02 (2H, m), of 6.49-6,53 (1H, m), 7,50-7,56 (1H, m), 7,82-7,87 (1H, m), 8,21 compared to 8.26 (2H, m), charged 8.52-to 8.57 (1H, m), 11,73 (1H, user. C).

(Example 58)

1-[2-(4-Methylpiperazin-1-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-[2-(4-methylpiperazin-1-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (177 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and 2-(4-methylpiperazin-1-yl)ethanol (147 mg).

1H-NMR (CDCl3) δ: 1.70 to to 1.79 (2H, m), 1,81 is 1.91 (2H, m), 2,25-of 2.34 (2H, m), of 2.28 (3H, s), a 2.36-2,48 (6H, m), 2,50-2,62 (4H, m)to 2.67 (2H, t, J=6.4 Hz), of 3.96 (2H, t, J=6.4 Hz), 5,98-of 6.02 (1H, m), 7,42 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[2-(4-methylpiperazin-1-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (173 mg) was obtained as a light yellow amorphous substance of the act is obom, similar to the one used in stage 3 of example 1 using the compound obtained in the above stage 1 (177 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (123 mg).

1H-NMR (CDCl3) δ: 1,72-of 1.81 (2H, m), 1,86-of 1.94 (2H, m), and 2.27 (3H, s), 2,30-of 2.38 (2H, m), 2,38-2,70 (10H, m), was 2.76 (2H, t, J=6.8 Hz), 4,07 (2H, t, J=6.8 Hz), 6,05-6,09 (1H, m), 6,59 (1H, DD, J=3,4, 2.0 Hz), 7,38-7,42 (1H, m,), 7,47 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz), of 8.28 (1H, d, J=1.7 Hz), and 8.50 (1H, d, J=2.2 Hz), 9,37 (1H, user. C).

Stage 3

1-[2-(4-Methylpiperazin-1-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (74 mg) was obtained as a colourless solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (173 mg).

MS (ESI) m/z: 378 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H23N7O 378,20290; found: 378,20325.

1H-NMR (DMSO-d6) δ: 2,10 (3H, s), 2,17 to 2.35 (4H, m), 2,62 (2H, t, J=6.2 Hz), 3,28-3,30 (4H, m), of 3.97 (2H, t, J=6.2 Hz), of 6.49-of 6.52 (1H, m), 7,51-rate of 7.54 (1H, m), a 7.85-7,87 (1H, m), 8,23 (2H, DD, J=5,7, 1.8 Hz), 8,54 (1H, d, J=2.0 Hz), for 11.55 (1H, user. C)11,73 (1H, user. C).

(Example 59)

1-[2-(4-Acetylpiperidine-1-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Tert-butyl 4-[2-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-ethyl]piperazine-1-carboxylate

Specified the title compound (551 mg) was obtained by way similar to the one used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (400 mg)and tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (468 mg).

1H-NMR (CDCl3) δ: of 1.45 (9H, s), 1.70 to of 1.78 (2H, m), 1,82-1,90 (2H, m), 2,27-of 2.34 (2H, m), 2,38 is 2.44 (2H, m), of 2.44-2.50 (4H, m), 2,68 (2H, t, J=6.5 Hz), 3,36-to 3.41 (4H, m), of 3.97 (2H, t, J=6.5 Hz), 5,98-of 6.02 (1H, m), 7,37 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz).

Stage 2

6-Bromo-1-(2-piperazine-4-ileti]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (249 mg) was obtained as a colorless amorphous substance in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (551 mg).

1H-NMR (CDCl3) δ: 2,49-to 2.57 (4H, m), 2,68 (2H, t, J=6.2 Hz), is 2.88 (4H, t, J=4.9 Hz), of 3.95 (2H, t, J=6.2 Hz), 7,41 (1H, d, J=2.0 Hz), of 8.04 (1H, d, J=2.0 Hz).

Stage 3

1-[2-(4-Acetylpiperidine-1-yl)ethyl]-6-bromo-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above step 2 (100 mg), was dissolved in chloroform (10 ml). Was added dropwise while cooling with ice, triethylamine (0,128 ml) and acetyl chloride (0,026 ml) and the mixture was stirred at the same temperature for 30 minutes and then stirred at room temperature for 1.5 hours. The reaction solution was concentrated and the residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain specified in the title the information of the compound (114 mg) as a colorless solid.

1H-NMR (CDCl3) δ: of 2.08 (3H, s), 2,52 (2H, t, J=5,1 Hz), to 2.57 (2H, t, J=5.0 Hz), of 2.72 (2H, t, J=6.2 Hz), 3,44 (2H, t, J=4,8 Hz), of 3.60 (2H, t, J=5.0 Hz), 3,98 (2H, t, J=6.2 Hz), 7,37 (1H, d, J=2.0 Hz), 8,08 (1H, d, J=2.0 Hz), 10,70 (1H, user. C).

Stage 4

1-[2-(4-Acetylpiperidine-1-yl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (38 mg) was obtained as a colourless solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (114 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (91 mg).

MS (ESI) m/z: 406 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H23N7O2406,19915; found: 406,19850.

1H-NMR (DMSO-d6) δ: 1,96 (3H, s), 2,38-of 2.50 (4H, m), 2.63 in-a 2.71 (2H, m), 3,32-to 3.38 (4H, m), 3,97-of 4.05 (2H, m), of 6.49-6,53 (1H, m), 7,51-of 7.55 (1H, m), a 7.85-of 7.90 (1H, m), by 8.22-of 8.27 (2H, m), 8,53-to 8.57 (1H, m), 11,57 (1H, user. C)11,73 (1H, user. C).

(Example 60)

1-{2-[4-(Methylsulphonyl)piperazine-1-yl]ethyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-1-{2-[4-(methylsulphonyl)piperazine-1-yl]ethyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in stage 2 of example 59 (100 mg), was dissolved in chloroform (10 ml). Was added dropwise while cooling with ice, triethylamine (0,128 ml) and methanesulfonamide (0.036 ml) and the mixture was stirred at the same the temperature for 10 minutes and then stirred at room temperature for 1.5 hours. The reaction solution was concentrated and the residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (82 mg) as a colorless solid.

1H-NMR (CD3OD) δ: 2.63 in (4H, t, J=4.9 Hz), is 2.74 (2H, t, J=6,1 Hz), 2,80 (3H, s), 3,15 (4H, t, J=4.9 Hz), was 4.02 (2H, t, J=6,1 Hz), 7,71-7,73 (1H, m), 7,88 (1H, user. C)8,02 (1H, d, J=2.0 Hz).

Stage 2

1-{2-[4-(Methylsulphonyl)piperazine-1-yl]ethyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (68 mg) was obtained as a colourless solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (82 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (59 mg).

MS (ESI) m/z: 442 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H23N7O3S 442,16613; found: 442,16415.

1H-NMR (DMSO-d6) δ: 2,55-2,62 (4H, m), 2,68 is 2.75 (2H, m), 2,80 (3H, s), 3.00 and-of 3.07 (4H, m), 3,97-Android 4.04 (2H, m), of 6.49-6,53 (1H, m), 7,53 (1H, t, J=2.7 Hz), 7,86-of 7.90 (1H, m), by 8.22 compared to 8.26 (2H, m), 8,54-8,56 (1H, m), 11,57 (1H, user. C)11,73 (1H, user. C).

(Example 61)

1-{[TRANS-4-Hydroxymitragynine-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

Methyl 4-oxitetraciclina-3-carboxylate

55% sodium Hydride (1.9 g) suspended in tetrahydrofuran (30 ml), and within 10 minutes was added dropwise a solution of methylglucose (3.6 g) in tetrahydrofuran (10 ml). After stirring at room temperature for 30 minutes, the solvent was evaporated to obtain a colorless solid. This substance was suspended in dimethyl sulfoxide (20 ml) was added methyl acrylate (4.3 ml) under cooling with ice. The mixture was stirred at the same temperature for 15 minutes and then stirred at room temperature for 45 minutes. The reaction solution was poured into 5% aqueous solution of sulfuric acid (50 ml), then was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (3.0 g) as a colourless solid.

1H-NMR (CDCl3) δ: 3,54 (1H, t, J=8,3 Hz), with 3.79 (3H, s), of 3.97 (1H, d, J=17,1 Hz), of 4.05 (1H, d, J=17,1 Hz), 4,43-of 4.54 (2H, m).

Stage 2

Methyl 4-hydroxymitragynine-3-carboxylate

The compound obtained in the above stage 1 (1.6 g)was dissolved in methanol (150 ml). Under ice cooling was added sodium borohydride (0.6 g) and the mixture was stirred at the same temperature for 2 hours. To the reaction solution was added water, then was extracted with chloroform. The organic layer was washed with saturated saline and then dried nadaswaram sodium sulfate and the solvent was evaporated to obtain specified in the title compound (1.3 g).

Stage 3

Methyl TRANS-4-{[tert-butyl(dimethyl)silyl]oxy}tetrahydrofuran-3-carboxylate

Methyl CIS-4-{[tert-butyl(dimethyl)silyl]oxy}tetrahydrofuran-3-carboxylate

The compound obtained in the above step 2 (1.3 g)was dissolved in N,N-dimethylformamide (10 ml). Added imidazole (1.2 g) and tert-butyldimethylsilyl chloride (1.7 g) and the mixture was stirred at room temperature for 17 hours. Added water, then was extracted with ethyl acetate. The organic layer was washed with water and saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was separated and purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the title compounds, respectively, TRANS-isomer (0.6 g) and the CIS isomer (1.4 g), as colorless oils.

the TRANS-isomer

1H-NMR (CDCl3) δ: 0,07 (3H, s), and 0.08 (3H, s)to 0.88 (9H, s), 2.95 and-a 3.01 (1H, m), 3,62 (1H, DD, J=9,0, and 3.7 Hz), and 3.72 (3H, s), 3,91-4,00 (2H, m), 4,14 (1H, t, J=8,3 Hz), 4.63 to-and 4.68 (1H, m).

CIS-isomer

1H-NMR (CDCl3) δ: 0,05 (3H, s)0,06 (3H, s)0,86 (9H, s), 3,07 is 3.15 (1H, m), 3,70 (3H, s), and 3.72 (1H, d, J=2.4 Hz), of 3.94 (1H, DD, J=9,4, a 4.3 Hz), 4,01 (1H, t, J=8,3 Hz), 4,20 (1H, t, J=9.0 Hz), 4,59 with 4.64 (1H, m).

Stage 4

[TRANS-4-{[tert-butyl(dimethyl)silyl]oxy}tetrahydrofuran-3-yl]methanol

Specified in the title compound (0.16 g) was obtained as colorless oil by the way, analogichnymi in stage 2 of example 33, using the compound obtained in the above stage 3 (0,59 g).

1H-NMR (CDCl3) δ: 0,07 (3H, s), and 0.08 (3H, s)to 0.89 (9H, s), 1.77 in (1H, user. C), 2,24 to 2.35 (1H, m), 3,54 at 3.69 (4H, m), 3,93 (1H, DD, J=9,1, 5,2 Hz), a 4.03 (1H, DD, J=8,8, 6,8 Hz), 4,21-4,27 (1H, m).

Stage 5

6-Bromo-1-{[TRANS-4-{[tert-butyl(dimethyl)silyl]oxy}tetrahydrofuran-3-yl]methyl}-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (229 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and the compound obtained in the above stage 4 (160 mg).

1H-NMR (CDCl3) δ: -0,10 (3H, s)-0,06 (3H, s)to 0.80 (9H, s), 1,71-to 1.79 (2H, m), 1,83 is 1.91 (2H, m), 2,28-of 2.34 (2H, m), 2,38 at 2.45 (2H, m), 2.57 m)-2,66 (1H, m), 3,60-3,71 (3H, m)to 3.92 (1H, DD, J=14,4, 9,0 Hz)to 4.01 (1H, DD, J=of 9.3 and 6.1 Hz), 4,13 (1H, DD, J=9,3, 5,1 Hz), 4,20-4,24 (1H, m), 5,98-6,01 (1H, m), 7,32 (1H, d, J=2.0 Hz), 8,11 (1H, d, J=2.0 Hz).

Stage 6

1-{[TRANS-4-{[tert-Butyl(dimethyl)silyl]oxy}tetrahydrofuran-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (191 mg) was obtained as a pale yellow amorphous substance in a way similar to stage 3 of example 1 using the compound obtained in the above stage 5 (229 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (165 mg).

1H-NMR (CDCl3) δ: -0,09 (3H, s)-0,06 (3H, s), 78 (9H, C), 1,74-to 1.82 (2H, m), 1,86-of 1.95 (2H, m), 2,31-of 2.38 (2H, m), 2,46-of 2.54 (2H, m), 2,67 was 2.76 (1H, m), the 3.65 (1H, DD, J=9,3, 2,9 Hz), to 3.73-3,82 (2H, m), 3,98-4,08 (2H, m), 4,17 (1H, DD, J=9,3, 5,1 Hz), 4.26 deaths-4,30 (1H, m), 6,05-6,10 (1H, m), 6,60 (1H, DD, J=3,4, 2.0 Hz), 7,42 (1H, d, J=1.7 Hz), 7,44-7,47 (1H, m), of 8.09 (1H, d, J=2.0 Hz), with 8.33 (1H, d, J=1.7 Hz), 8,51 (1H, d, J=2.0 Hz), 10,48 (1H, user. C).

Stage 7

1-{[TRANS-4-Hydroxymitragynine-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (61 mg) was obtained as a light brown powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (191 mg).

MS (ESI) m/z: 352 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H17N5O3352,14096; found: 352,14065.

1H-NMR (DMSO-d6) δ: 3,44-3,50 (1H, m), 3,55 (1H, DD, J=8,7, 3.8 Hz), 3,69-3,97 (5H, m), 4,05 is 4.13 (1H, m), 4,94-4,99 (1H, m), 6,51 (1H, d, J=2.7 Hz), 7,52 (1H, d, J=2,9 Hz), 7,80-7,87 (1H, m), by 8.22-of 8.25 (2H, m), 8,54 (1H, d, J=2.0 Hz), 11,73 (1H, user. C).

(Example 62)

1-{[CIS-4-Hydroxymitragynine-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

CIS-4-(Hydroxymethyl)tetrahydrofuran-3-ol

Specified in the title compound (0.17 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained h is stage 3 of example 61 (0,42 g).

1H-NMR (CDCl3) δ: 2,37-2,47 (1H, m), 3,61-of 3.95 (7H, m), is 4.21 (1H, user. C), 4,45-4,50 (1H, m).

Stage 2

CIS-4-({[tert-Butyl(diphenyl)silyl]oxy}methyl)tetrahydrofuran-3-yl]methyl}tetrahydrofuran-3-ol

The compound obtained in the above stage 1 (0.39 g)was dissolved in dichloromethane (20 ml). Under ice cooling was added triethylamine (0,92 ml), dimethylaminopyridine (0.04 g) and tert-butyldiphenylsilyl (1,02 ml) and the mixture was stirred at room temperature for 65 hours. To the reaction solution was added water, then was extracted with chloroform. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.0 g) as a colourless oil.

1H-NMR (CDCl3) δ with 1.07 (9H, s), 2,37-2,48 (1H, m), 2,85-of 2.93 (1H, m)to 3.67 (1H, t, J=8,8 Hz), of 3.77-3,86 (2H, m), 3,86-of 3.94 (3H, m), 4,46-to 4.52 (1H, m), of 7.36-7,47 (6H, m), of 7.64-of 7.69 (4H, m).

Stage 3

tert-Butyl(diphenyl){[CIS-4-(Tetra-2H-Piran-2-yloxy)tetrahydrofuran-3-yl]methoxy}silane

The compound obtained in the above stage 2 (149 mg), was dissolved in dichloromethane (10 ml). Added 3,4-dihydro-2H-Piran (0,11 ml) and p-toluensulfonate acid (14 mg) and the mixture was stirred at room temperature for 21 hours. To the reaction is aStore was added saturated aqueous sodium bicarbonate solution, then was extracted with chloroform. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (126 mg) as a colourless oil.

1H-NMR (CDCl3) δ: of 1.05 (9H, s), 1,34-of 1.81 (6H, m), 2,43-2,61 (1H, m), 3,36-3,51 (1H, m), 3,56-4,10 (7H, m), 4,33-to 4.46 (1H, m), 4,62-and 4.68 (1H, m), 7,34-7,46 (6H, m), 7,62-of 7.70 (4H, m).

Stage 4

[CIS-4-(Tetra-2H-Piran-2-yloxy)tetrahydrofuran-3-yl]methanol

The compound obtained in the above stage 3 (126 mg)was dissolved in tetrahydrofuran (5 ml). Added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (0,32 ml) and the mixture was stirred at room temperature for one hour. To the reaction solution was added saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (49 mg) as a colourless oil.

1H-NMR (CDCl3) δ: 1,49-of 1.66 (4H, m), 1.70 to to 1.87 (2H, m), 2,43-2,62 (1,5H, m), 3,48-to 3.58 (1,5H, m), 3,59-4,01 (7H, m), 4,36-4,43 (0,5H, m), 4,45-of 4.54 (1H, is), 4,70-4,74 (0,5H, m).

Stage 5

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[CIS-4-(Tetra-2H-Piran-2-yloxy)tetrahydrofuran-3-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (91 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (71 mg)and the compound obtained in the above stage 4 (49 mg).

1H-NMR (CDCl3) δ: 1,46-of 1.95 (10H, m), 2.26 and-of 2.38 (2H, m), a 2.36-2.49 USD (2H, m), was 2.76-2,89 (1H, m), 3,42 of 3.56 (1H, m), 3,74-4,16 (6H, m), 4,24-4,33 (0,5H, m), 4,45-4,50 (0,5H, m), to 4.52-4,58 (0,5H, m), with 4.64 (0,5H, DD, J=of 4.9 and 2.7 Hz), 5,98-6,05 (1H, m), of 7.36 (0,5H, d, J=2.0 Hz), 7,46 (0,5H, d, J=2.0 Hz), 7,56 (0,5H, d, J=2.0 Hz), 8,06-8,10 (1H, m), 8,11 (0,5H, d, J=2.0 Hz).

Stage 6

3-Cyclohex-1-EN-1-yl-1-{[CIS-4-(Tetra-2H-Piran-2-yloxy)tetrahydrofuran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (82 mg) was obtained as a pale yellow oil in a way similar to stage 3 of example 1 using the compound obtained in the above stage 5 (91 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (69 mg).

1H-NMR (CDCl3) δ: 1.30 and of 1.66 (4H, m), 1,67-of 1.84 (4H, m), 1,86-of 1.95 (2H, m), 2,30-of 2.38 (2H, m), 2,46-of 2.54 (2H, m), 2,84-2,96 (1H, m), 3,39-3,55 (1H, m), 3,70-3,78 (0,5H, m), 3,79-4,08 (5,0H, m), 4,11-4,39 (2H, m), 4,51-4,56 (0,5H, m), 4,56-4,60 (0,5H, m), 4,65-4,69 (0,5H, m), 6,06-6,10 (1H, m), 6,58-of 6.61 (1H, m), 7,41-7,45 (1,5H, m), EUR 7.57 (0,5H, d, J=2.0 Hz), 8.07-a to 8.12 (1H, m), 8,30 (1H, t, J=2.2 Hz), 8,49-8,55 (1H, m), 9,83-9,92 (1, m).

Stage 7

1-{[CIS-4-Hydroxymitragynine-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (22 mg) was obtained as a light brown powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (82 mg).

MS (ESI) m/z: 352 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H17N5O3352,14096; found: 352,14081.

1H-NMR (DMSO-d6) δ: 2,53-of 2.64 (1H, m), 3,56-3,66 (2H, m), of 3.73-3,81 (2H, m), 3,94-4,06 (2H, m), 4,15-is 4.21 (1H, m), 5.17 to at 5.27 (1H, m), 6,51 (1H, d, J=3,4 Hz), 7,50-rate of 7.54 (1H, m), 7,86-7,89 (1H, m), 8,24 (2H, d, J=2.0 Hz), 8,54 (1H, d, J=2.0 Hz), 11,66 (1H, user. C)11,73 (1H, user. C).

(Example 63)

1-{[CIS-4-Methoxyacridine-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

tert-Butyl{[CIS-4-methoxyacridine-3-yl]methoxy}diphenylsilane

CIS-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)tetrahydrofuran-3-yl]methyl}tetrahydrofuran-3-ol, obtained in stage 2 of example 62 (0,93 g), was dissolved in tetrahydrofuran (30 ml). In nitrogen atmosphere at 0°C was added 55% sodium hydride (228 mg) and the mixture was stirred at the same temperature for five minutes and then stirred at room temperature for 30 minutes. We use the and methyliodide (1,62 ml) and the mixture was stirred at room temperature for 15 hours. Was added water under ice cooling and then the tetrahydrofuran drove away. The residue was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (0,91 g) as a colourless solid.

1H-NMR (CDCl3) δ: of 1.05 (9H, s), 2,47-of 2.58 (1H, m), with 3.27 (3H, s), 3,59-the 3.65 (1H, m), and 3.72 (1H, DD, J=10,0, 7,3 Hz), with 3.79 (1H, DD, J=10,0, 4,2 Hz), 3,88-3,99 (4H, m), 7,34 was 7.45 (6H, m), of 7.64-7,71 (4H, m).

Stage 2

[CIS-4-Methoxyacridine-3-yl]methanol

Specified in the title compound (171 mg) was obtained as colorless oil by the method similar to that applied in stage 4 of example 11 using the compound obtained in the above stage 1 (0,91 g).

1H-NMR (CDCl3) δ: 2,42-of 2.54 (1H, m)of 2.75 (1H, user. C)3,37 (3H, s), 3,76-of 3.96 (6H, m), to 4.01-4.09 to (1H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[CIS-4-methoxyacridine-3-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (334 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (250 mg)and the compound obtained in the above stage 2 (169 mg).

1H-NMR (CDCl3) δ: 1,68-to 1.79 (2H, m), 1,83 is 1.91 (2H, m, of 2.27 to 2.35 (2H, m), 2,38 is 2.46 (2H, m), 2,78-2,89 (1H, m), and 3.31 (3H, s), 3,65-of 3.78 (3H, m), 3,91-4,07 (4H, m), 5,99-6,04 (1H, m), 7,47 (1H, d, J=1.2 Hz), of 8.09 (1H, t, J=1.0 Hz).

Stage 4

3-Cyclohex-1-EN-1-yl-1-{[CIS-4-methoxyacridine-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (246 mg) was obtained as a pale orange amorphous material in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (334 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (240 mg).

1H-NMR (CDCl3) δ: 1,73-of 1.81 (2H, m), 1,86-of 1.94 (2H, m), 2,30-of 2.38 (2H, m), 2,48-of 2.54 (2H, m), 2,89-of 3.00 (1H, m), 3,29 (3H, s), of 3.73-3,81 (2H, m), 3,81-3,86 (1H, m), 3,98-4,07 (3H, m), 4,18 (1H, DD, J=14,3, 7.9 Hz), 6,07-6,11 (1H, m), 6,60 (1H, DD, J=3,5, 1.8 Hz), 7,43-7,47 (1H, m), 7,55 (1H, d, J=2.0 Hz), to 8.12 (1H, d, J=2.0 Hz), 8,32 (1H, d, J=2.0 Hz), 8,54 (1H, d, J=2.2 Hz), of 10.58 (1H, user. C).

Stage 5

1-{[CIS-4-Methoxyacridine-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (50 mg) was obtained as colorless powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (246 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H19N5O3366,15661; found: 366,15583.

1H-NMR (DMSO-d6) δ: 2,73-to 2.85 (1H, m), 3,23 (3H, s)to 3.58 (1H, t, J=8,9 Hz), to 3.67 (1H, DD, J=9,6, 3.5 Hz), 3,76 (1H, t, J=7.8 Hz), 3,83-3,91 (2H, m), of 3.97 (1H, DD, J=14,0, and 8.4 Hz), 4,07 (1H, DD, J=14,5, 6.5 Hz), 6,51 (1H, d, J=3,4 Hz), 7,52 (1H, t, J=2.7 Hz), 7,81-to 7.84 (1H, m), by 8.22 compared to 8.26 (2H, m), 8,55 (1H, d, J=2.0 Hz), 11,60 (1H, user. C)11,73 (1H, user. C).

(Example 64)

1-{[TRANS-4-Methoxyacridine-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

TRANS-4-(Hydroxymethyl)tetrahydrofuran-3-ol

Specified in the header of the connection (between 0.30 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained in stage 3 of example 61 (0,89 g).

1H-NMR (CDCl3) δ: 1,66-1,72 (1H, m), 2,31-to 2.42 (1H, m), 3,55-3,74 (4H, m), a 3.87 (1H, t, J=5.6 Hz), of 3.94 (1H, DD, J=9,8, 5,1 Hz), 4.09 to (1H, DD, J=8,8, 7,3 Hz)to 4.33 (1H, user. C).

Stage 2

TRANS-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)tetrahydrofuran-3-yl]methyl}tetrahydrofuran-3-ol

Specified in the title compound (0.39 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 62, using the compound obtained in the above stage 1 (0,30 g).

1H-NMR (CDCl3) δ: of 1.06 (9H, s), 2,19 (1H, user. C)2,34 is 2.43 (1H, m), 3,55-3,63 (2H, m), 3,64-3,70 (2H, m), 3,82 (1H, DD, J=9,6, 5.0 Hz), Android 4.04 (1H, DD, J=8,8, 7,6 Hz), 4,27-to 4.33 (1H, m), of 7.36-7,46 (6H, m), 7,62-to 7.68 (4H, m).

Stage 3

tert-Butyl{[TRANS-4-methoxyacridine-3-yl]methoxy}diphenylsilane

Specified in is the head of the compound (0.35 g) was obtained as colorless oil by the way similar to the one used in stage 1 of example 63, using the compound obtained in the above stage 2 (0.39 g).

1H-NMR (CDCl3) δ: of 1.06 (9H, s), 2.40 a-2,50 (1H, m), 3,29 (3H, s), 3,52-to 3.67 (3H, m), of 3.73-a-3.84 (3H, m), of 3.97 (1H, DD, J=8,9, 7,0 Hz), 7,34-7,47 (6H, m), 7,60-to 7.68 (4H, m).

Stage 4

[TRANS-4-Methoxyacridine-3-yl]methanol

Specified in the title compound (0.075 g) was obtained as colorless oil by the method similar to that applied in stage 4 of example 62, using the compound obtained in the above stage 3 (0.35 g).

1H-NMR (CDCl3) δ: 1,25 (1H, user. C), 2,38-2,47 (1H, m)to 3.34 (3H, s), 3,59-to 3.67 (3H, m), of 3.78 (1H, DD, J=9,8, 2.7 Hz), 3,81-of 3.85 (1H, m), 3,91 (1H, DD, J=9,5, 5,1 Hz), 4,00 (1H, DD, J=9,0, 6,8 Hz).

Stage 5

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[TRANS-4-methoxyacridine-3-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (118 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (166 mg)and [TRANS-4-methoxyacridine-3-yl]methanol obtained in the above stage 4 (75 mg).

1H-NMR (CDCl3) δ: 1.70 to to 1.79 (2H, m), 1,82 is 1.91 (2H, m), 2,28-of 2.34 (2H, m), 2,37 at 2.45 (2H, m), 2,68-2,78 (1H, m), 3,21 (3H, s), 3,62 of 3.75 (2H, m), of 3.78 (1H, DD, J=9,9, 3.1 Hz), 3,81-of 3.85 (1H, m), 3,91-4,00 (2H, m), 4.09 to (1H, DD, J=9,9, 5,2 Hz), 5,98-6,03 (1H, m), 7,35 (1H, d, J=2.0 Hz), to 8.12 (1H, d, J=2.0 Hz).

Stage 6

3-Cyclohex-1-EN-1-yl-1-{[TRANS-4-methoxyacridine-3-yl]methyl}-6-(1H-feast of the olo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (102 mg) was obtained as a pale yellow solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 5 (119 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (197 mg).

1H-NMR (CDCl3) δ: 1,73-to 1.82 (2H, m), 1,87-of 1.95 (2H, m), 2,31-of 2.38 (2H, m), 2,46 of $ 2.53 (2H, m), 2,79-2,87 (1H, m), up 3.22 (3H, s), and 3.72 (1H, DD, J=9,0, and 3.7 Hz), of 3.77-3,86 (2H, m), a 3.87-to 3.92 (1H, m), of 3.97-4.09 to (2H, m), of 4.12 (1H, DD, J=10,0, 5,1 Hz), 6,06-6,10 (1H, m), 6,60 (1H, DD, J=3,5, 1.8 Hz), 7,41-7,44 (2H, m), of 8.09 (1H, d, J=2.0 Hz), 8,32 (1H, d, J=2.0 Hz), 8,51 (1H, d, J=2.0 Hz), 9,84 (1H, user. C).

Stage 7

1-{[TRANS-4-Methoxyacridine-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (26 mg) was obtained as a pale orange powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (102 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H19N5O3366,15661; found: 366,15599.

1H-NMR (DMSO-d6) δ: 2,70-and 2.79 (1H, m), 3,03 (3H, s), of 3.54 (1H, DD, J=9,0, 4,2 Hz), 3,66 (1H, DD, J=9,8 and 2.2 Hz), 3,79-of 3.95 (5H, m), 6,51 (1H, DD, J=3,4, 1.7 Hz), 7,51-rate of 7.54 (1H, m), of 7.96 (1H, d, J=2.0 Hz), 8,24-of 8.28 (2H, m), 8,56 (1H, d, J=2.2 Hz), 11,67 (1H, user. C)11,74 (1H, user. C).

(Example 65)

1-{[CIS-5-Hydroxyacetamido-2H-Piran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]feast the DIN-2-he

and its enantiomer

Stage 1

Methyl 4-aniline-2,5-dihydrofuran-3-carboxylate

The compound obtained in stage 1 of example 61 (1.0 g), was dissolved in toluene (20 ml). Added aniline (0,76 ml) and p-toluensulfonate acid (0,011 g) and the mixture was heated under reflux with dehydration for 17 hours. After cooling, the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.2 g) as a solid light yellow color.

1H-NMR (CDCl3) δ: 3,76 (3H, s), 4,80 (2H, t, J=3.2 Hz), of 4.95 (2H, t, J=3.2 Hz), 6,93 (2H, d, J=8,3 Hz), was 7.08 (1H, t, J=7,3 Hz), 7,30 (2H, t, J=7.9 Hz), 9,10 (1H, user. C).

Stage 2

Methyl (4Z)-3-(iodomethyl)-4-(phenylimino)tetrahydrofuran-3-carboxylate

Tert-piperonyl potassium (5,2 g) suspended in benzene (40 ml). Solution was added the compound obtained in the above stage 1 (8.5 g)and 18-crown-6 (12.3 g) in benzene (40 ml) under nitrogen atmosphere and the mixture was stirred at room temperature for 30 minutes. Then added diameter (9.4 ml) and the mixture was stirred at room temperature for 24 hours. The reaction solution was diluted with ethyl acetate, washed with 5% aqueous sodium thiosulfate solution and saturated saline and then dried over anhydrous sodium sulfate and dissolve the spruce was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (3.5 g) as a solid light yellow color.

1H-NMR (CDCl3) δ: 3,61 (1H, d, J=10.1 Hz), with 3.79 (1H, d, J=10.1 Hz), 3,85 (3H, s), 4,17 (1H, d, J=9.9 Hz), 4,19 (1H, d, J=16.0 Hz), 4,28 (1H, d, J=16.0 Hz), 4,60 (1H, d, J=9.9 Hz), 6,78-6,83 (2H, m), 7,11-7,16 (1H, m), 7,29-to 7.35 (2H, m).

Stage 3

Methyl 5-exoterica-2H-Piran-3-carboxylate

The compound obtained in the above stage 2 (3.5 g)was dissolved in benzene (300 ml). Was added dropwise a solution of hydride tri-n-butyanova (3,9 ml) and azobisisobutyronitrile (0.3 g) in benzene (300 ml) at reflux under nitrogen atmosphere for 6 hours. Then the mixture was heated under reflux for 2 hours. After cooling, the solvent was evaporated. The residue was diluted with chloroform, washed with 10% aqueous solution of fluoride potassium and saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.3 g) as a pale yellow oil.

1H-NMR (CDCl3) δ: 2,69 (1H, DD, J=17,0, 6.2 Hz), 2,84 (1H, DD, J=17,1, 7,3 Hz), 3,14 is 3.23 (1H, m in), 3.75 (3H, s), of 4.00 (1H, DD, J=11,7, and 6.6 Hz), Android 4.04 (2H, s)4,08 (1H, DD, J=11,7, 4,4 Hz).

Stage 4

Methyl CIS-5-[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-carboxylate

Methyl TRANS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-carboxylate

The compound obtained in the above stage 3 (1.6 g)was dissolved in methanol (100 ml). Was added under ice cooling sodium borohydride (0.5 g) and the mixture was stirred at the same temperature for 3 hours. To the reaction solution was added water, then neutralized with acetic acid. Methanol drove away. To the remaining solution was added sodium chloride and then was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to give the crude alcohol (1.5 g).

Both in the title compound, CIS-isomer) (2.1 g) and TRANS-isomer (0.18 g)was obtained as colorless oil by a method similar to those used in stage 3 of example 61, using the resulting crude alcohol (1.5 g).

CIS-isomer

1H-NMR (CDCl3) δ: 0,06 (3H, s)of 0.07 (3H, s)to 0.88 (9H, s), 1,54-of 1.66 (1H, m), 2,24 to 2.35 (1H, m), 2,64 was 2.76 (1H, m), to 3.02 (1H, t, J=10.4 Hz), 3,32 (1H, t, J=11,1 Hz), 3,64-of 3.77 (1H, m), 3,66 (3H, s), 3,80-are 3.90 (1H, m), 4,01-4,10 (1H, m).

the TRANS-isomer

1H-NMR (CDCl3) δ: 0,08 (3H, s), and 0.08 (3H, s)of 0.90 (9H, s), 1,76-of 1.85 (1H, m), 2.06 to to 2.15 (1H, m), 2,87-2,95 (1H, m)to 3.41 (1H, DD, J=11,2, 5,9 Hz), 3,59-the 3.65 (1H, m), 3,70 (3H, s), of 3.77-3,86 (2H, m), a 3.87-of 3.94 (1H, m).

Stage 5

CIS-5-{[tert-buildkey)silyl]oxy}tetrahydro-2H-Piran-3-carboxylic acid

Methyl CIS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-carboxylate obtained in the above stage 4 (300 mg)was dissolved in methanol (15 ml). Added 1 N. aqueous sodium hydroxide solution (3.2 ml) and the mixture was stirred at room temperature for 24 hours. Methanol drove and then to the residue was added 1 N. aqueous solution of hydrochloric acid (3.2 ml), then was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated to obtain specified in the title compound (267 mg) as colorless solids.

1H-NMR (CDCl3) δ: x 0.07 (6H, d, J=3,9 Hz)to 0.88 (9H, s), 1,61-1,72 (1H, m), 2,24 is 2.33 (1H, m), 2,66 was 2.76 (1H, m), 3,10 (1H, DD, J=10,9, 9,2 Hz), 3,42 (1H, t, J=10,7 Hz), 3,68-of 3.78 (1H, m), 3,79-3,86 (1H, m), a 4.03 (1H, DDD, J=11,4, 4,3, 1.2 Hz), 10,52 (1H, user. C).

Stage 6

[CIS-5-{[tert-Butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-yl]methanol

The compound obtained in the above stage 5 (267 mg), was dissolved in tetrahydrofuran (10 ml). Under ice cooling was added triethylamine (0,214 ml) and ethylchloride (amount of 0.118 ml). The mixture was stirred at the same temperature for 30 minutes and then the precipitate was removed by filtration. To the filtrate under ice cooling was added dropwise a solution of sodium borohydride (77,7 mg) in water (2 ml) and the mixture was stirred at room temperature in ECENA 22 hours. Tetrahydrofuran drove and then to the residue was added saturated aqueous sodium bicarbonate solution, then was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (251 mg) as a colourless oil.

1H-NMR (CDCl3) δ: x 0.07 (6H, d, J=3.2 Hz), to 0.88 (9H, s), 1,13-of 1.27 (1H, m), 1,84-of 1.95 (1H, m), 1,95-2,05 (1H, m), 3.00 and is 3.15 (2H, m), 3,45-3,55 (2H, m), 3,67 is 3.76 (1H, m), 3,79-of 3.85 (1H, m), 3,90-of 3.96 (1H, m).

Stage 7

6-Bromo-1-{[CIS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-yl]methyl}-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (405 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and the compound obtained in the above stage 6 (251 mg).

1H-NMR (CDCl3) δ: x 0.07 (6H, d, J=1.0 Hz), to 0.88 (9H, s)and 1.51-of 1.53 (1H, m), 1.70 to of 1.78 (2H, m), 1,82 is 1.91 (2H, m), 1,99-2,07 (1H, m), 2,17-of 2.27 (1H, m), 2,27-of 2.34 (2H, m), 2,38 is 2.44 (2H, m), 3,11-is 3.21 (2H, m), 3,65-3,93 (5H, m), 5,98-of 6.02 (1H, m), 7,31 (1H, d, J=2.0 Hz), 8,10 (1H, d, J=2.0 Hz).

Stage 8

1-{[CIS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridi the-2-he

Specified in the title compound (204 mg) was obtained as a pale yellow oil in a way similar to stage 3 of example 1 using the compound obtained in the above stage 7 (405 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (204 mg).

1H-NMR (CDCl3) δ: 0,06 (6H, d, J=2,4 Hz)to 0.88 (9H, s), of 1.34 to 1.47 (1H, m), 1,73-to 1.82 (2H, m), 1,86-of 1.94 (2H, m), is 2.05 and 2.13 (1H, m), 2,25-of 2.38 (3H, m), 2,46 of $ 2.53 (2H, m)and 3.15 (1H, DD, J=10,7, 8.5 Hz), 3,24 (1H, DD, J=11,2, 9.5 Hz), 3,70-of 3.85 (4H, m)to 3.99 (1H, DD, J=14,4, 9.0 Hz), 6,06-6,10 (1H, m), 6,60 (1H, DD, J=3,5, 1.8 Hz), 7,41 (1H, d, J=2.0 Hz), 7,42-7,46 (1H, m), of 8.09 (1H, d, J=2.0 Hz), 8,31 (1H, d, J=1.7 Hz), charged 8.52 (1H, d, J=2.2 Hz), 10,18 (1H, user. C).

Stage 9

1-{[CIS-5-Hydroxyacetamido-2H-Piran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (10 mg) was obtained as a colourless solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 8 (204 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H19N5O3366,15661; found: 366,15645.

1H-NMR (CD3OD) δ: 1,25-of 1.36 (1H, m), 2,07-of 2.16 (1H, m), 2,22 to 2.35 (1H, m), is 3.08 (1H, t, J=10.0 Hz), up 3.22 (1H, t, J=10,6 Hz), to 3.58-3,68 (1H, m), of 3.77-to 3.92 (3H, m), of 3.96 (1H, DD, J=14,5, 7,7 Hz), to 6.58 (1H, d, J=3,4 Hz), 7,46 (1H, d, J=3,4 Hz), 7,82 (1H, d, J=1.7 Hz), 8,24 (1H, d, J=1.7 Hz), of 8.27 (1H, d, J=2.0 Hz), 8,46 (1H, d, J=2.0 Hz).

(Example 66)

1-{[TRANS-5-Hydroxyacetamido-2H-Piran-3-yl]IU the Il}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

TRANS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-carboxylic acid

Specified in the title compound (165 mg) was obtained as colorless oil in a way similar to stage 5 of example 65, using methyl TRANS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-carboxylate (184 mg)obtained in stage 4 of example 65.

1H-NMR (CDCl3) δ: 0,08 (6H, d, J=3.2 Hz), of 0.90 (9H, s), 1,79-to 1.87 (1H, m), 2,07-of 2.16 (1H, m), 2.91 in-2,99 (1H, m)to 3.41 (1H, DD, J=11,4, 5.7 Hz), the 3.65 (1H, DD, J=11,2, 2.7 Hz), 3,79-of 3.96 (3H, m).

Stage 2

[TRANS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-yl]methanol

Specified in the title compound (154 mg) was obtained in a way similar to the stage 6 of example 65, using the compound obtained in the above stage 1 (165 mg).

1H-NMR (CDCl3) δ: 0,06 (6H, s)to 0.89 (9H, s), 1,68 (2H, t, J=5.7 Hz), 2,07-of 2.20 (1H, m), of 2.38 (1H, user. C)of 3.42 (1H, DD, J=11,4, 5.7 Hz), 3,47-3,55 (1H, m), 3,57-of 3.64 (3H, m), of 3.77 (1H, DD, J=11,4, 3.5 Hz), 3,80-3,88 (1H, m).

Stage 3

6-Bromo-1-{[TRANS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-yl]methyl}-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (167 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (183 mg)and the compound obtained is as described above stage 2 (154 mg).

1H-NMR (CDCl3) δ: 0,03 (6H, d, J=11.7 Hz)to 0.85 (9H, s), 1,64 is 1.70 (2H, m), 1.70 to of 1.78 (2H, m), 1,82-1,90 (2H, m), 2,27-of 2.34 (2H, m), 2,37 is 2.43 (2H, m), 2,45 is 2.55 (1H, m), 3,42 (2H, TD, J=10,9, 6.2 Hz), 3,64-to 3.73 (2H, m), 3,78 (1H, DD, J=14,3, 8,2 Hz), a 3.87 (1H, DD, J=14,2, 7,3 Hz), 3,89-of 3.97 (1H, m), 5,97-of 6.02 (1H, m), 7,32 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=2.0 Hz).

Stage 4

1-{[TRANS-5-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-Piran-3-yl]methyl}-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (138 mg) was obtained as a pale yellow oil in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (167 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (117 mg).

1H-NMR (CDCl3) δ: 0,01 (6H, d, J=11.5 Hz), of 0.82 (9H, s), 1,67-of 1.81 (4H, m), 1.85 to was 1.94 (2H, m), 2,30-is 2.37 (2H, m), 2,46 of $ 2.53 (2H, m), 2,55-of 2.66 (1H, m), 3,40-of 3.53 (2H, m), 3,66-of 3.78 (2H, m), 3,84-4,01 (3H, m), 6,05-6,10 (1H, m), 6,58-6,60 (1H, m), the 7.43 (1H, d, J=1.7 Hz), 7,44-7,47 (1H, m), of 8.09 (1H, d, J=2.0 Hz), 8,31 (1H, d, J=1.7 Hz), 8,51 (1H, d, J=2.0 Hz), of 10.76 (1H, user. C).

Stage 5

1-{[TRANS-5-Hydroxyacetamido-2H-Piran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (50 mg) was obtained as light brown powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (138 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+ calculated: C 19H19N5O3366,15661; found: 366,15579.

1H-NMR (DMSO-d6) δ: 1,07-of 1.13 (1H, m), 1,50-of 1.62 (2H, m), 3,51 (2H, DD, J=11,5, 2,4 Hz)and 3.59 (2H, DD, J=11,2, 2,9 Hz), 3,69-with 3.79 (3H, m)and 4.65 (1H, user. C)6,50 (1H, d, J=3,4 Hz), 7,51 (1H, d, J=3,4 Hz), to 7.67-7,72 (1H, m), 8,16-8,19 (1H, m), 8,21 (1H, d, J=2.2 Hz), charged 8.52 (1H, d, J=2.2 Hz), 11,71 (1H, user. C).

(Example 67)

1-{[CIS-5-Methoxytyramine-2H-Piran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

Tert-butyl(dimethyl)({CIS-5-[(tetrahydro-2H-Piran-2-yloxy)methyl]tetrahydro-2H-Piran-3-yl}oxy)silane

Specified in the title compound (222 mg) was obtained as colorless oil by the method similar to those used in stage 3 of example 62, using the compound obtained in stage 6 of example 65 (180 mg).

1H-NMR (CDCl3) δ: 0,06 (12H, d, J=3,4 Hz)to 0.88 (18H, s), 1,13-of 1.29 (2H, m), 1,46 is 1.91 (9H, m), 1,95-of 2.09 (4H, m), 2.95 and-3,10 (4H, m), 3,17-3,29 (2H, m), 3.46 in-was 4.02 (14H, m), 4,51-of 4.57 (2H, m), 4,93-to 4.98 (1H, m).

Stage 2

CIS-5-[(Tetrahydro-2H-Piran-2-yloxy)methyl]tetrahydro-2H-Piran-3-ol

Specified in the title compound (136 mg) was obtained as colorless oil by the method similar to that applied in stage 4 of example 62, using the compound obtained in the above stage 1 (222 mg).

1H-NMR (CDCl3) δ: 1,17-1,32 (2H, m), 1,47 is 1.86 (6H, m), 1,97-to 2.18 (2H, m), is 2.37 (1H, user. C)3,02-to 3.33 (3H, m), 3.46 in-was 4.02 (5H, m), 4.53-in-4,60 (1H, m).

Stage 3

CIS-3-Met the xylose-5-[(tetrahydro-2H-Piran-2-yloxy)methyl]tetrahydro-2H-Piran

Specified in the title compound (123 mg) was obtained as colorless oil by the method similar to those used in stage 1 of example 63, using the compound obtained in the above stage 2 (136 mg).

1H-NMR (CDCl3) δ: 1,08-1,20 (1H, m), 1,47-to 1.63 (4H, m), 1,64-of 1.74 (1H, m), 1,74 is 1.86 (1H, m), 1,96-of 2.08 (1H, m), 2,14 was 2.25 (1H, m), 2,99 is 3.15 (2H, m), 3,21-3,37 (2H, m)to 3.38 (3H, s), 3.46 in-3,55 (1H, m), 3,56-3,66 (1H, m), 3,76-3,86 (1H, m), 3,91-4,10 (2H, m), to 4.52-4,58 (1H, m).

Stage 4

[CIS-5-Methoxytyramine-2H-Piran-3-yl]methanol

The compound obtained in the above stage 3 (115 mg), was dissolved in methanol (10 ml). Added p-toluensulfonate acid (10 mg) and the mixture was stirred at room temperature for 14 hours. After distillation of the methanol, the residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (68 mg) as a colourless oil.

1H-NMR (CDCl3) δ: 1,14 of 1.28 (1H, m), 1,83-of 1.97 (2H, m), 2,13-of 2.20 (1H, m), 3,11-up 3.22 (2H, m), 3,28-3,37 (1H, m)to 3.38 (3H, s), 3,53-3,61 (2H, m), 3,91-was 4.02 (2H, m).

Stage 5

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[CIS-5-methoxytyramine-2H-Piran-3-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (114 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (137 mg)and the compound obtained in the above stage 4 (68 mg).

H-NMR (CDCl3) δ: of 1.34 to 1.47 (1H, m), 1,70-1,80 (2H, m), 1,81 is 1.91 (2H, m), 2,07-2,17 (1H, m), 2,18-of 2.36 (3H, m), 2,38 at 2.45 (2H, m), 3,26-to 3.36 (3H, m)to 3.38 (3H, s), 3,71-a 3.83 (2H, m), 3,86-of 3.95 (2H, m), 5,98-6,03 (1H, m), 7,38 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=2.0 Hz).

Stage 6

3-Cyclohex-1-EN-1-yl-1-{[CIS-5-methoxytyramine-2H-Piran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (113 mg) was obtained as a pale yellow oil in a way similar to stage 3 of example 1 using the compound obtained in the above stage 5 (114 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (99 mg).

1H-NMR (CDCl3) δ: 1,37 is 1.48 (1H, m), 1,72-of 1.81 (2H, m), 1,83-of 1.95 (2H, m), 2,15-of 2.23 (1H, m), 2,28-is 2.37 (3H, m), 2,47 of $ 2.53 (2H, m), 3.27 to 3,37 (3H, m), 3,37 (3H, s), 3,78-a 4.03 (4H, m), 6,06-6,11 (1H, m), 6,60 (1H, DD, J=3,5, 1.8 Hz), 7,45-of 7.48 (2H, m), 8,11 (1H, d, J=2.0 Hz), 8,31 (1H, d, J=2.0 Hz), 8,53 (1H, d, J=2.2 Hz), 10,90 (1H, user. C).

Stage 7

1-{[CIS-5-Methoxytyramine-2H-Piran-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (68 mg) was obtained as a light brown powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (113 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,07-to 1.21 (1H, m), 2,09-of 2.23 (2H, m), 2,95 (1H, t, J=10.1 Hz), 3,10 (1H, t, J=10.5 Hz), 3,17-of 3.25 (1H, m), 3,24 (3H, s), 3,67-of 3.95 (4H, m), 6,50-6,53 (1H, m), 7,51-of 7.55 (1H, m), 7,88-of 7.90 1H, m), 8,24 (2H, d, J=1.7 Hz), 8,54 (1H, d, J=2.0 Hz), are 11.62 (1H, user. C)11,74 (1H, user. C).

(Example 68)

1-[(4-Methoxytyramine-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

4 Methoxytyramine-2H-Piran-4-carbaldehyde

Specified in the header of the connection (of 0.47 g) was obtained by the method similar to those used in stage 1 of example 25 using (4 methoxytyramine-2H-Piran-4-yl)methanol obtained by the method described in WO 2008/029825 (0.68 g).

Stage 2

5-Bromo-N3-[(4-methoxytyramine-2H-Piran-4-yl)methyl]pyridine-2,3-diamine

Specified in the title compound (0.11 g) was obtained by the method similar to those used in stage 1 of example 24, using 2,3-diamino-5-bromopyridine (0.56 g) and the compound obtained in the above stage 1 (0,47 g).

MS (ESI) m/z: 316 (M+H)+.

Stage 3

6-Bromo-1-[(4-methoxytyramine-2H-Piran-4-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (0.12 g) was obtained in a way similar to step 2 of example 1 using the compound obtained in the above stage 2 (0.11 g).

MS (ESI) m/z: 344 (M+H)+.

Stage 4

1-[(4-Methoxytyramine-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (45 mg) was obtained in a way similar is in stage 3 of example 1, using the compound obtained in the above stage 3 (115 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (82 mg).

HRMS (ESI) [(M+H)+] calculated: C20H22N5O3380,17226; found: 380,17388.

1H-NMR (DMSO-d6) δ: 1,59-of 1.73 (4H, m), 3,40 (3H, s), 3,42 is 3.57 (2H, m), 3,61-3,70 (2H, m), 3,91-3,98 (2H, m), of 6.49-is 6.54 (1H, m), 7,50-7,58 (1H, m), 7,82 (1H, d, J=1,8 Hz), 8,19-of 8.27 (2H, m), and 8.50 (1H, DD, J=11,0, 1.8 Hz), 11,74 (1H, user. C).

(Example 69)

1-[(4-Porterage-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Methyl 4-Porterage-2H-Piran-4-carboxylate

Specified in the title compound (0.4 g) was obtained as a pale yellow solid by the method similar to those used in stage 1 of example 51, using methyl tetrahydro-2H-Piran-4-carboxylate (2.0 g).

1H-NMR (CDCl3) δ: 1,83-of 1.93 (2H, m), 2,07-of 2.28 (2H, m), 3,71-with 3.79 (2H, m), 3,82 (3H, s), 3,88 (2H, DDD, J=11,7, 5,1, 2,4 Hz).

Stage 2

(4 Porterage-2H-Piran-4-yl)methanol

Specified in the title compound (0.15 g) was obtained as colorless oil by the method similar to those used in stage 2 of example 33 using the compound obtained in the above stage 1 (0,41 g).

1H-NMR (CDCl3) δ: 1,63-1,89 (4H, m)2,00 (1H, user. C), 3,61 (2H, d, J=20.7 Hz), to 3.73 (2H, TD, J=11,3, 2.4 Hz), 3,79-a 3.87 (2H, m).

Stage 3

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(4-porter the hydro-2H-Piran-4-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (353 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and the compound obtained in the above stage 2 (134 mg).

1H-NMR (CDCl3) δ: 1.70 to to 1.82 (4H, m), 1,82 is 2.01 (4H, m), and 2.27 to 2.35 (2H, m), 2,38 is 2.46 (2H, m), 3,70 (2H, m), 3,82-are 3.90 (2H, m)to 4.01 (2H, d, J=22.9 Hz), 5,99-6,05 (1H, m), of 7.48 (1H, m), 8,11 (1H, d, J=1.7 Hz).

Stage 4

3-Cyclohex-1-EN-1-yl-1-[(4-Porterage-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (200 mg) was obtained as a pale yellow solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (353 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (181 mg).

1H-NMR (CDCl3) δ: 1,73-to 2.06 (8H, m), 2,31-2,39 (2H, m), 2,46 of $ 2.53 (2H, m), and 3.72 (2H, m), 3,84-3,93 (2H, m), 4,07-4,17 (2H, m), 6,06-6,11 (1H, m), 6,59 (1H, DD, J=3,4, 2.0 Hz), 7,39-the 7.43 (1H, m), EUR 7.57 (1H, m), of 8.09 (1H, J=the 2.2 Hz), 8,32 (1H, J=2.0 Hz), 8,51 (1H, J=2.0 Hz), 9,50 (1H, user. C).

Stage 5

1-[(4-Porterage-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (127 mg) was obtained as a light brown powder in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (200 is g).

MS (ESI) m/z: 368 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H18FN5O2368,15119; found: 368,15228.

1H-NMR (DMSO-d6) δ: 1,66-of 1.95 (4H, m), 3,47 of 3.56 (2H, m), 3.72 points-of 3.80 (2H, m), 4,14 (2H, J=22,2 Hz), 6,50-is 6.54 (1H, m), 7,53 (1H, m), to 7.77-7,80 (1H, m), 8,19 (1H, d, J=2.1 Hz), compared to 8.26 (1H, d, J=1.7 Hz) and 8.50 (1H, d, J=2.1 Hz), 11,71 (1H, user. C)of 11.75 (1H, user. C).

(Example 70)

1-[(2,2-Dimethylether-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

2,2-Dimethylether-2H-Piran-4-carbonitril

To a solution of 2,2-dimethylether-4H-Piran-4-it (350 mg) in dimethoxyethane (10 ml) with stirring was added n-toluensulfonate (693 mg) and tert-butanol (438 μl). The three parts were added tert-piperonyl potassium (766 mg), cooling at -20°C. the Mixture was heated to room temperature and then was stirred for 18 hours. Added diethyl ether and the mixture filtered through celite. Then the solvent was evaporated under reduced pressure to obtain specified in the title compound (321 mg).

1H-NMR (CDCl3) δ: 1,21 (3H, s)of 1.28 (3H, s), 1,69-of 1.93 (4H, m), 2,82-2,89 (1H, m), 3,61-3,66 (1H, m), of 3.77-3,81 (1H, m).

Stage 2

2,2-Dimethylether-2H-Piran-4-carboxylic acid

To the compound obtained in the above stage 1 (321 mg)was added to 2.25 M aqueous solution of potassium hydroxide (6 ml) and the mixture was heated with about ATiM fridge over night. The reaction solution was left to cool to room temperature and then washed with diethyl ether and was added concentrated hydrochloric acid until then, until the reaction solution became acid, then was extracted with ethyl acetate. The organic layer was washed with saturated saline solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain specified in the title compound (264 mg).

1H-NMR (CDCl3) δ: 1,23 (3H, s)of 1.26 (3H, s), 1,55-1,71 (2H, m), equal to 1.82 (2H, t, J=13,7 Hz), 2,69 is 2.75 (1H, m), 3,64 at 3.69 (1H, m), 3,78-3,81 (1H, m).

Stage 3

(2,2-Dimethylether-2H-Piran-4-yl)methanol

Specified in the title compound (220 mg) was obtained in a way similar to step 2 of example 33 using the compound obtained in the above stage 2 (264 mg).

1H-NMR (CDCl3) δ: 1,08-1,25 (8H, m), 1,58-of 1.65 (2H, m), 1,92-of 1.94 (1H, m), of 3.46 (2H, t, J=6.6 Hz), 3,66-3,71 (1H, m), 3,76-3,81 (1H, m).

Stage 4

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(2,2-dimethylether-2H-Piran-4-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (255 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (150 mg)and the compound obtained in the above stage 3 (103 mg).

MS (ESI) m/z: 420 (M+H)+.

1H-NMR (CDCl3) δ: 1,19 (3H, s)of 1.23 (3H, s), 53-1,56 (2H, m), 1,72-to 1.77 (2H, m), 1,84-1,89 (2H, m), 2,22 is 2.33 (3H, m), 2.40 a is 2.44 (2H, m), 3,59-of 3.78 (5H, m), 6,01-of 6.02 (1H, m), 7,28 (1H, d, J=1.7 Hz), 8,10 (1H, d, J=1.7 Hz).

Stage 5

3-Cyclohex-1-EN-1-yl-1-[(2,2-dimethylether-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (176 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (255 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (108 mg).

MS (ESI) m/z: 458 (M+H)+.

1H-NMR (CDCl3) δ: 1,19 (3H, s), 1,24 (3H, s), 1,57-of 1.62 (2H, m), of 1.76 and 1.80 (2H, m), 1,88-of 1.93 (2H, m), 2,32-is 2.37 (3H, m), 2,49-2,52 (2H, m), 3,63 (1H, t, J=12.3 Hz), to 3.73-3,82 (3H, m), between 6.08-6,10 (1H, m), 6,60-of 6.61 (1H, m), 7,35-7,37 (1H, m), 8,07 (1H, s), 8,29-8,30 (1H, m), 8,49-and 8.50 (1H, m), 9,07 (1H, user. C).

Stage 6

1-[(2,2-Dimethylether-2H-Piran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (57 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 5 (176 mg).

MS (ESI) m/z: 378 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C21H23N5O2378,19300; found: 378,19044.

1H-NMR (DMSO-d6) δ: 1,09 (3H, s), 1,10-1,25 (2H, m), 1,11 (3H, s)of 1.47 (2H, t, J=11.2 Hz), 2,22-2,31 (1H, m), 3,47-to 3.52 (1H, m)and 3.59 (1H, DD, J=12,0, 4.0 Hz), and 3.72 (2H, d, J=7,4 Hz), 6,51-of 6.52 (1H, m), 7,52-rate of 7.54 (1H, m), to $ 7.91-a 7.92 (1H, m), 8,23-of 8.25 (2H, m), 8,55 (1H, d, J=23 Hz), 11,59 (1H, user. C)of 11.75 (1H, user. C).

(Example 71)

1-{[(2R-4r-6S)-2,6-Dimethylether-2H-Piran-4-yl]methyl}-6-(1H-pyrrolo-[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[(2R-4r-6S)-2,6-dimethylether-2H-Piran-4-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (152 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (150 mg)and [(2R-4r-6S)-2,6-dimethylether-2H-Piran-4-yl]methanol (103 mg)obtained by the method described in WO 2007/070201.

MS (ESI) m/z: 420 (M+H)+.

1H-NMR (CDCl3) δ: 0,97-of 1.05 (2H, m), 1,19 (3H, s)of 1.20 (3H, s), 1,58-of 1.62 (2H, m), 1,72-to 1.77 (2H, m), 1,84-1,89 (2H, m), 2,10-2,19 (1H, m), 2,29 is 2.33 (2H, m), 2,41 is 2.44 (2H, m), 3,42-of 3.48 (2H, m), of 3.69 (2H, d, J=7,4 Hz), 6,01-of 6.02 (1H, m), 7,26-7,27 (1H, m), 8,10 (1H, d, J=1.7 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-{[(2R-4r-6S)-2,6-dimethylether-2H-Piran-4-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (150 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (152 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (97 mg).

MS (ESI) m/z: 458 (M+H)+.

1H-NMR (CDCl3) δ: 1,02-of 1.09 (2H, m), 1,19 (3H, s)of 1.20 (3H, s), 1,65 by 1.68 (2H, m), 1,75-1,80 (2H, m), 1,88-of 1.93 (2H, m), 2,18-of 2.27 (1H, m), 2,33-of 2.36 (2H, m, 2,49-2,52 (2H, m), 3,44-of 3.48 (2H, m), 3,80 (2H, d, J=6.9 Hz), between 6.08 and 6,09 (1H, m), 6,60 (1H, DD, J=3,4, 1.7 Hz), 7,35 (1H, d, J=1.7 Hz), 8,07 (1H, d, J=2.3 Hz), 8,29 (1H, d, J=1.7 Hz), 8,49 (1H, d, J=2.3 Hz), 8,76 (1H, user. C).

Stage 3

1-{[(2R-4r-6S)-2,6-Dimethylether-2H-Piran-4-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (65 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above step 2 (150 mg).

MS (ESI) m/z: 378 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C21H23N5O2378,19300; found: 378,19088.

1H-NMR (DMSO-d6) δ: 0,86-0,93 (2H, m)of 1.05 (3H, s)of 1.06 (3H, s), 1,54-of 1.57 (2H, m), 2,12-of 2.21 (1H, m), 3.33 and-3,39 (2H, m), 3,74 (2H, d, J=7,4 Hz), 6,51-of 6.52 (1H, m), 7,52-7,53 (1H, m), of 7.90 (1H, s), 8,24 is 8.25 (2H, m), 8,55 (1H, d, J=2.3 Hz), 11,59 (1H, user. C)11,74 (1H, user. C).

(Example 72)

6-(3-Amino-1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

2-Fluoro-5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]benzonitrile

Specified in the title compound (56 mg) was obtained in a way similar to stage 3 of example 1, using (3-cyano-4-forfinal)boric acid (35 mg) and the compound obtained in stage 1 of example 4 (60 mg).

MS (ESI) m/z: 353 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H18FN4O2353,14138; on the Deno: 353,14387.

1H-NMR (DMSO-d6) δ: 1,21-to 1.38 (2H, m), 1,43-and 1.54 (2H, m), 2,01-2,17 (1H, m), 3,19-3,30 (1H, m), 3,71-3,88 (4H, m), to 7.61-of 7.69 (1H, m), to 7.93 (1H, d, J=1,8 Hz), 8,12-to 8.20 (1H, m), 8,28-of 8.33 (2H, m), 11,72 (1H, user. C).

Stage 2

6-(3-Amino-1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above stage 1 (52 mg), prepared in the form of a solution in ethanol (3 ml). Added hydrazinoacetate (36 μl) and the mixture was heated under reflux for 3 hours. Additionally added hydrazinoacetate (72 μl) and the mixture was heated under reflux for 24 hours. Adding more hydrazinoacetate (144 μl) and the mixture was heated under reflux for 24 hours. After that, the reaction solution was concentrated and purified by thin-layer chromatography (elwira a mixture of methanol-dichloromethane) to obtain the specified title compound (27 mg).

MS (ESI) m/z: 365 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N6O2365,17260; found: 365,17303.

1H-NMR (DMSO-d6) δ: 1,22-of 1.39 (2H, m), 1,46-of 1.56 (2H, m), 2,02-2,17 (1H, m), 3,19-3,30 (2H, m), 3.72 points-a 3.87 (4H, m), of 5.40 (2H, s), 7,32 (1H, d, J=8.7 Hz), EUR 7.57 (1H, DD, J=8,7, 1.8 Hz), to 7.77 (1H, d, J=1,8 Hz), 8,00 (1H, s), 8,18 (1H, d, J=2.3 Hz), 11,44 (1H, user. C)for 11.55 (1H, user. C).

(Example 73)

6-Pyrazolo[1,5-a]pyrimidine-6-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-(Tributylstannyl)pyrazolo[1,5-a]pyrimidine

6-Bromopyrazole[1,5-a]pyrimidine (150 mg) was dissolved in toluene (3 ml). Added hexamethylditin (0,188 ml) and tetranitroaniline palladium (92 mg) and the mixture was stirred at 115°C for 2 hours. The reaction solution was cooled to room temperature and then the solvent was evaporated. The obtained residue was purified by thin-layer chromatography (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (145 mg).

MS (ESI) m/z: 284 (M+H)+.

1H-NMR (CDCl3) δ: 0,43 (9H, s), 6,64-of 6.65 (1H, m), 8.07-a 8,07 (1H, m), to 8.41-to 8.41 (1H, m), 8,59 at 8.60 (1H, m).

Stage 2

6-Pyrazolo[1,5-a]pyrimidine-6-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Bis(triphenylphosphine)palladium(II) dichloride (36 mg) was added to a solution of the compound obtained in the above stage 1 (145 mg)and the compound obtained in stage 1 of example 4 (60 mg)in N,N-dimethylformamide (2.6 ml) in nitrogen atmosphere. The mixture was stirred under microwave radiation at 150°C for 15 minutes. The reaction solution was concentrated under reduced pressure and the residue was purified by thin-layer chromatography (elwira a mixture of methanol-dichloromethane) to obtain the specified title compound (28 mg).

MS (ESI) m/z: 351 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H19N6O2351,15695; Nai is prohibited: 351,16154.

1H-NMR (DMSO-d6) δ: 1,21-to 1.38 (2H, m), 1,45-1,55 (2H, m), 2,04-2,19 (1H, m), 3,19-of 3.25 (2H, m), 3,74 (2H, d, J=7,3 Hz), 3,78-3,86 (2H, m), 6,77-to 6.80 (1H, m), of 8.04 (1H, d, J=1,8 Hz), compared to 8.26 (1H, d, J=2.3 Hz), 8,40 (1H, d, J=1,8 Hz), 8,99 (1H, d, J=2.3 Hz), at 9.53-9,49 (1H, m), 11,73 (1H, s).

(Example 74)

6-(1H-Pyrazolo[3,4-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[3,4-b]pyridine

5-Bromo-1H-pyrazolo[3,4-b]pyridine (200 mg) was dissolved in N,N-dimethylformamide (5 ml). Was added 55% sodium hydride at 0°C (53 mg) and the mixture was stirred at the same temperature for five minutes and then stirred at room temperature for 20 minutes. Was added 2-(chloromethoxy)ethyltrimethoxysilane (0,213 ml) and the mixture was stirred at 0°C for 2 hours. Under ice cooling was added a saturated aqueous solution of ammonium chloride, then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (0,224 g).

1H-NMR (CDCl3) δ: 0,00 (9H, s), 0,96-1,00 (2H, m), 3,68-and 3.72 (2H, m), 5,90 (2H, s), 8,07 (1H, s), of 8.27 (1H, d, J=2.2 Hz), 8,65 (1H, d, J=2.2 Hz).

Stage 2

5-Tributylstannyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[3,4-b]pyridine

Listed is in the title compound (115 mg) was obtained by way similar to the one used in stage 1 of example 73, using the compound obtained in the above stage 1 (116 mg).

1H-NMR (CDCl3) δ: 1,71-of 1.81 (4H, m), 3.43 points (3H, s), 3,64-to 3.67 (2H, m), 3,76-with 3.79 (2H, m)to 4.01 (2H, s), 7,40 (1H, d, J=2.0 Hz), 8,10 (1H, d, J=2.0 Hz), of 9.56 (1H, s).

Stage 3

1-(Tetrahydro-2H-Piran-4-ylmethyl)-6-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[3,4-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (13 mg) was obtained in a way similar to step 2 of example 73, using the compound obtained in the above stage 2 (85 mg)and the compound obtained in stage 1 of example 4 (60 mg).

MS (ESI) m/z: 481 (M+H)+.

1H-NMR (CDCl3) δ: 0,04 (9H, s), 0,95-of 1.03 (2H, m), 1,49 is 1.58 (2H, m), 1,63-of 1.73 (2H, m), 2,12-to 2.29 (1H, m), 3,35 is-3.45 (2H, m), 3,69 is 3.76 (2H, m), 3,82-to 3.89 (2H, m), 3,98-4,07 (2H, m), 5,96 (2H, d, J=1.4 Hz), 7,37-7,41 (1H, m), 8,19 (1H, d, J=1,8 Hz), 8,23 compared to 8.26 (1H, m), 8,28-8,31 (1H, m), at 8.60 (1H, user. C)8,83-8,79 (1H, m).

Stage 4

6-(1H-Pyrazolo[3,4-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 3 (13 mg)in tetrahydrofuran (1 ml) was added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (0.3 ml) and the mixture was heated under reflux for 8.5 hours. Addition was added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (1 ml) and the mixture was heated with reverse you can see what these lamps for 8 hours. The reaction solution was concentrated under reduced pressure and the residue was purified by thin-layer chromatography (elwira a mixture of methanol-dichloromethane) to obtain the specified title compound (6 mg).

MS (ESI) m/z: 351 (M+H)+.

HRMS (ESI) [M+H]+calculated: C18H19N6O2351,15695; found: 351,15591.

1H-NMR (DMSO-d6) δ: 1,24-of 1.37 (4H, m), 1,44-to 1.61 (4H, m), 2,03-2,17 (1H, m), 3,10-up 3.22 (2H, m), 3,70-a 3.87 (4H, m), 7,95 (1H, d, J=1,8 Hz), 8,21 (1H, s), of 8.28 (1H, d, J=1.4 Hz), 8,51 (1H, d, J=2.3 Hz), 8,87 (1H, d, J=2,3 Hz), 11,64 (1H, user. C).

(Example 75)

6-(5H-Pyrrolo[2,3-b]pyrazin-2-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Tert-butyl 2-bromo-5H-pyrrolo[2,3-b]pyrazin-5-carboxylate

Specified in the title compound (244 mg) was obtained in a way similar to stage 1 of example 35 using 2-bromo-5H-pyrrolo[2,3-b]pyrazin (168 mg).

1H-NMR (CDCl3) δ: 1,68 (9H, s)of 6.71 (1H, J=4,1 Hz), of 7.96 (1H, J=4,1 Hz), 8,49 (1H, s).

Stage 2

3-Cyclohex-1-EN-1-yl-6-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (131 mg) was obtained as a pale yellow solid in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (120 mg)and the compound obtained in stage 4 note the RA 35 (216 mg).

MS (ESI) m/z: 432 (M+H)+.

1H-NMR (CDCl3) δ: 1,46-of 1.57 (2H, m), 1.60-to a rate of 1.67 (2H, m), 1,75-1,80 (2H, m), 1,88-of 1.94 (2H, m), 2,18-of 2.24 (1H, m), 2,32-is 2.37 (2H, m), 2,48-2,52 (2H, m), 3,37 (2H, m), a 3.87 (2H, d, J=7,1 Hz)to 3.99 (2H, DD, J=11,6, 2,8 Hz), between 6.08-6,10 (1H, m), 6,82-6,83 (1H, m), to 7.67 (1H, m), of 7.96 (1H, d, J=1.7 Hz), 8,64 (1H, d, J=2.0 Hz), 8,71 (1H, s), 8,99 (1H, m).

Stage 3

6-(5H-Pyrrolo[2,3-b]pyrazin-2-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (54 mg) was obtained in the form of solid opal in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (130 mg).

HRMS (ESI) [M+H]+calculated: C18H19N6O2351,15695; found: 351,15860.

MS (ESI) m/z: 351 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,29-to 1.38 (2H, m), 1,50-1,55 (2H, m), 2,07 and 2.13 (1H, m), 3,22-3,30 (2H, m), 3,79-of 3.85 (4H, m), 6,69-6,70 (1H, m), to $ 7.91 (1H, m), 8,17 (1H, d, J=2.0 Hz), 8,67 (1H, d, J=1.7 Hz), 8,89 (1H, s), 11,70 (1H, ), 12,11 (1H, m).

(Example 76)

6-(7H-Pyrrolo[2,3-c]pyridazin-3-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

4-Bromo-6-chloropyridin-3-amine

3-Amino-6-chloro pyridazine (7,87 g) was dissolved in methanol (115 ml). Was added sodium bicarbonate (10.2 g) and then was added dropwise bromine (3.1 ml) and the mixture was stirred at room temperature for 16 hours. The reaction solution was filtered and then diluted with water (500 m is) and the aqueous layer was extracted with ethyl acetate three times. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (5.2 g) as a solid brown color.

MS (ESI) m/z: 208 (M+H)+.

1H-NMR (DMSO-d6) δ: 6,98 (2H, user. C)of 8.00 (1H, s).

Stage 2

6-Chloro-4-[(trimethylsilyl)ethinyl]pyridazin-3-amine

Specified in the title compound (1.06 g) was obtained in the form of a solid brown color in a way similar to step 2 of example 36 using 4-bromo-6-chloropyridin-3-amine obtained in the above stage 1 (1.5 g).

MS (ESI) m/z: 226 (M+H)+.

1H-NMR (CDCl3) δ: 0,29 (9H, s), lower than the 5.37 (2H, user. C)to 7.25 (1H, s).

Stage 3

N-Acetyl-N-{6-chloro-4-[(trimethylsilyl)ethinyl]pyridazin-3-yl}ndimethylacetamide

The compound obtained in the above stage 2 (1.06 g)was dissolved in dichloromethane (20 ml). Sequentially added pyridine (0,57 ml) and acetylchloride (0.33 ml) under ice cooling and the mixture was stirred at room temperature overnight. The reaction solution was washed with water and saturated saline solution in this order and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified of chromatogra what s on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (0.45 g) as a solid light yellow color.

MS (ESI) m/z: 310 (M+H)+.

1H-NMR (CDCl3) δ: 0,26 (9H, s), of 2.33 (6H, s), the 7.65 (1H, s).

Stage 4

6-Chloro-4-(2,2-dimethoxymethyl)pyridin-3-amine

The compound obtained in the above stage 3 (310 mg), was dissolved in methanol (20 ml). Was added potassium carbonate (276 mg) and the mixture was stirred over night. The reaction solution was concentrated, diluted with ethyl acetate, washed with water and saturated saline solution in this order and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (233 mg) as a brown oil.

MS (ESI) m/z: 218 (M+H)+.

1H-NMR (CDCl3) δ: 2,80 (2H, d, J=5.0 Hz), 3,41 (6H, s), a 4.53 (1H, t, J=5.0 Hz), a 5.25 (2H, s), to 7.09 (1H, s).

Stage 5

3-Chloro-7H-pyrrolo[2,3-c]pyridazin

The compound obtained in the above stage 4 (250 mg)was dissolved in ethanol (3 ml). Added 1 N. aqueous solution of hydrochloric acid (1 ml) and the mixture was stirred at 60°C for 3 hours. Addition was added concentrated hydrochloric acid (0.5 ml) and the mixture was stirred at 80°C for 2 hours. The reaction solution was neutralized with saturated aqueous sodium bicarbonate solution and then was extracted with a 10% mixture of methanol/chloroform three times and organic the ski layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (150 mg) in the form of a solid of light yellow color.

MS (ESI) m/z 154 (M+H)+.

1H-NMR (CDCl3) δ: is 6.54 (1H, d, J=3,4 Hz), 7,80 (1H, s), to 7.84 (1H, d, J=2.0 Hz), 12,01 (1H, user. C).

Stage 6

3-Cyclohex-1-EN-1-yl-6-(7H-pyrrolo[2,3-c]pyridazin-3-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (41 mg) was obtained as a pale yellow oil in a way similar to stage 3 of example 1 using the compound obtained in the above stage 5 (40 mg)and the compound obtained in stage 4 of example 35 (100 mg).

MS (ESI) m/z: 431 (M+H)+.

Stage 7

6-(7H-Pyrrolo[2,3-c]pyridazin-3-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (8 mg) was obtained in a solid green color in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (40 mg).

HRMS (ESI) [M+H]+calculated: C18H19N6O2351,15695; found: 351,15944.

MS (ESI) m/z: 351 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,29-to 1.38 (2H, m)and 1.51-of 1.55 (2H, m), of 2.08 and 2.13 (1H, m), 3,24-3,26 (2H, m), 3,80-of 3.85 (4H, m), 6,60 (1H, is, J=2,9 Hz), 7,92 (1H, m), 8,24 (1H, s), 8,40 (1H, s), 8,67 (1H, d, J=1.7 Hz), 11,70 (1H, s), 12,48 (1H, s).

(Example 77)

6-(3-Amino-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]boronic acid

Specified in the header connection (0,98 g) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in stage 4 of example 35 (1.56 g).

MS (ESI) m/z: 278 (M+H)+.

Stage 2

Tert-butyl (5-bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)carbamate

Specified in the title compound (350 mg) was obtained in the form of a solid brown color with a method similar to those used in stage 1 of example 35, using 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-amine, obtained by the method described in WO 2003/028724 (300 mg).

MS (ESI) m/z: 312 (M+H)+.

1H-NMR (DMSO-d6) δ: for 1.49 (9H, s), 7,54 (1H, s)8,23 (1H, d, J=2.3 Hz), to 8.41 (1H, s), 9,34 (1H, s), to 11.52 (1H, s).

Stage 3

Tert-butyl {5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-yl}carbamate

Specified in the title compound (90 mg) was obtained as a pale yellow solid in a way similar to stage 3 of example 1 using the compound obtained in the above step 2 (150 mg), and connect the s, obtained in the above stage 1 (173 mg).

MS (ESI) m/z: 465 (M+H)+.

1H-NMR (DMSO-d6) δ: of 1.29 to 1.37 (2H, m)of 1.50 (9H, s), 2,07 and 2.13 (1H, m), 3,22-to 3.36 (4H, m), of 3.77 (2H, m), 3,82-of 3.85 (2H, m), 7,53 (1H, s), a 7.85 (1H, d, J=1.7 Hz), to 8.20 (1H, d, J=1.7 Hz), 8,49 (1H, s), 8,53 (1H, d, J=1,7 Hz), 9,34 (1H, s), 11,35 (1H, s), of 11.61 (1H, s).

Stage 4

6-(3-Amino-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 3 (90 mg), in dichloromethane under ice cooling was added dropwise triperoxonane acid (1 ml) and the mixture was stirred for 6 hours while gradually warming to room temperature. Reaction solution was diluted with water, washed with chloroform. The aqueous layer was neutralized with saturated aqueous sodium bicarbonate solution and then was extracted with a 10% mixture of methanol/chloroform three times and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained solid was washed with ethyl acetate to obtain specified in the title compound (12 mg) as a solid light yellow color.

HRMS (ESI) [M+H]+calculated: C19H21N6O2365,17260; found: 365,17097.

MS (ESI) m/z: 365 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,27-to 1.38 (2H, m), 1,48-and 1.54 (2H, m), 2.05 is-of 2.16 (1H, m), 3,21-of 3.27 (2H, m), 3,76-with 3.79 (2H, m), 3,82-a-3.84 (2H, m), 4,35 (2H, user. C)of 6.71 (1H, d, J=1,8 Hz), 7,86 (1H, d, J=1,8 Hz), to 8.20 (1H, d, J=1,8 Hz), 8,23 (1H, d, J=2.3 Hz), 8,44 (1H, d, J=2.3 Hz), of 10.72 (1H, s), 11,59 (1H, s).

(Example 78)

6-(6-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-6-chloropyridin-2-amine

6-Chloropyridin-2-amine (2.0 g) was dissolved in acetonitrile (40 ml). Was added N-bromosuccinimide (3.1 g) and the mixture was stirred conditions dimming at room temperature for 13 hours. The reaction solution was concentrated and the obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (2.8 g).

MS (ESI) m/z: 207 (M+H)+.

Stage 2

5-Bromo-6-chloro-3-yodellin-2-amine

Specified in the title compound (1.8 g) was obtained by the method similar to those used in stage 1 of example 36, using the compound obtained in the above stage 1 (1.4 g).

MS (ESI) m/z: 333 (M+H)+.

1H-NMR (CDCl3) δ: of 5.05 (2H, user. C)to 7.99 (1H, s).

Stage 3

5-Bromo-6-chloro-3-[(trimethylsilyl)ethinyl]pyridine-2-amine

Specified in the title compound (1.8 g) was obtained in a way similar to step 2 of example 36, using the compound obtained in the above stage 2 (1.8 g).

MS (ESI) m/z: 303 (M+H)+.

1H-NMR (CDCl3) δ: 0,26 (9H, s), 5,11 (2H, user. C)of 7.70 (1H, s).

Stage 4

N-{5-Bromo-6-chloro-3-[(trimethylsilyl)ethinyl]pyridine-2-yl}ndimethylacetamide

The compound obtained in the above stage 3 (1.6 g)was dissolved in pyridine (0.8 ml) and dichloromethane (11 ml). Slowly under ice cooling was added dropwise acetylchloride (0.4 ml) and then the mixture was heated to room temperature and was stirred for 4 hours. To the reaction solution were added water. The organic layer was separated and dried over anhydrous sodium sulfate and the solvent was evaporated. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (0.95 g).

MS (ESI) m/z: 345 (M+H)+.

1H-NMR (CDCl3) δ: 0,29 (9H, s), of 2.53 (3H, s), of 7.90 (1H, s), 8,02 (1H, s).

Stage 5

5-Bromo-6-chloro-1H-pyrrolo[2,3-b]pyridine

The compound obtained in the above stage 4 (0.95 g)was dissolved in tetrahydrofuran (15 ml). Added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (5.5 ml) and the mixture was heated under reflux for 1.5 hours. The reaction solution was cooled to room temperature and then the tetrahydrofuran drove away. The residue was distributed between ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The obtained solid substance was collected by filtration from chloroform to obtain a decree of the tion in the title compound (0.4 g).

MS (ESI) m/z: 231 (M+H)+.

1H-NMR (DMSO-d6) δ: 6,47-of 6.49 (1H, m), to 7.59-to 7.59 (1H, m), 8,40-8,42 (1H, m), 12,04-12,06 (1H, m).

Stage 6

6-(6-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (11 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 77 (31 mg)and the compound obtained in the above stage 5 (26 mg).

MS (ESI) m/z: 384 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H19ClN5O2384,12273; found: 384,12511.

1H-NMR (DMSO-d6) δ: 1,24-1,32 (2H, m), 1,45-is 1.51 (2H, m), 1,99-2,07 (1H, m), up 3.22 (2H, t, J=11.2 Hz), 3,68-3,74 (2H, m), 3,80-a 3.83 (2H, m), is 6.54 (1H, d, J=3,4 Hz), 7,58-to 7.59 (1H, m), 7,69 (1H, s), of 7.97 (1H, d, J=1.7 Hz), 8,07 (1H, s), 11,67 (1H, s), 11,96 (1H, user. C).

(Example 79)

6-(6-Fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-6-fluoro-3-yodellin-2-amine

Specified in the title compound (1.7 g) was obtained by the method similar to those used in stage 1 of example 36 using 5-bromo-6-herperidin-2-amine, obtained by the method described in US 2008/221149 (1.3 g).

MS (ESI) m/z: 316 (M+H)+.

1H-NMR (CDCl3) δ: free 5.01 (2H, user. C)to 7.99 (1H, d, J=8,3 Hz).

Stage 2

5-Bromo-6-fluoro-3-[(trimethylsilyl)ethinyl]pyridine-2-amine

Specified in sagola the ECS compound (0.7 g) was obtained by way similar to the one used in stage 2 of example 36 using 5-bromo-6-fluoro-3-yodellin-2-amine obtained in the above stage 1 (1.3 g).

MS (ESI) m/z: 287 (M+H)+.

1H-NMR (CDCl3) δ: 0,27 (9H, s), 5,11 (2H, user. C), 7,74 (1H, d, J=8,5 Hz).

Stage 3

N-{5-Bromo-6-fluoro-3-[(trimethylsilyl)ethinyl]pyridine-2-yl}ndimethylacetamide

Specified in the title compound (165 mg) was obtained in a way similar to stage 4 of example 78, using the compound obtained in the above stage 2 (707 mg).

MS (ESI) m/z: 329 (M+H)+.

1H-NMR (CDCl3) δ: 0,29 (9H, s), 2,52 (3H, s), 7,95 (1H, d, J=8,3 Hz), 8,07 (1H, user. C).

Stage 4

5-Bromo-6-fluoro-1H-pyrrolo[2,3-b]pyridine

Specified in the title compound (81 mg) was obtained in a way similar to stage 5 of example 78, using the compound obtained in the above stage 3 (165 mg).

MS (ESI) m/z: 215 (M+H)+.

1H-NMR (CDCl3) δ: 6,48-of 6.49 (1H, m), 7,26-7,29 (1H, m), 8,17 (1H, d, J=8.5 Hz), 8,63 (1H, user. C).

Stage 5

6-(6-Fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (78 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 77 (119 mg)and 5-bromo-6-fluoro-1H-pyrrolo[2,3-b]pyridine obtained in the above stage 4 (77 mg).

MS (ESI) m/z: 368 (M+H)+.

HRMS (SI) [M+H] +calculated: C19H19FN5O2368,15228; found: 368,15482.

1H-NMR (DMSO-d6) δ: 1,26-of 1.35 (2H, m), 1,50 (2H, d, J=13,7 Hz), 2,04-2,10 (1H, m), 3,23 (2H, t, J=11.7 Hz), 3,74 is 3.76 (2H, m), 3,81-a-3.84 (2H, m), 6,56 (1H, s), 7,49-7,51 (1H, m), 7,78 (1H, s), 8,10 (1H, s), 8,23 compared to 8.26 (1H, m,), 11,66 (1H, user. C), 11.87 per (1H, user. C).

(Example 80)

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-indole-2-carboxylic acid

Stage 1

Benzyl 5-bromo-1H-indole-2-carboxylate

To a solution of 5-bromo-1H-indole-2-carboxylic acid (161 mg) in acetonitrile (3.5 ml) was added benzylbromide (160 ml) and 1,8-diazabicyclo[5,4,0]undec-7-ene (201 μl) at room temperature, then was stirred for 22.5 hours. The reaction solution was concentrated and separated by adding ethyl acetate and distilled water. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was led from a mixture of dichloromethane-hexane, collected by filtration and washed with hexane. This substance was dried under reduced pressure to obtain specified in the title compound (189 mg).

MS (ESI) m/z: 328 (M+H)+.

1H-NMR (CDCl3) δ: of 5.39 (2H, s), 7.18 in-7,21 (1H, m), 7,27-7,31 (1H, m), 7,34-of 7.48 (6H, m), 7,81-7,83 (1H, m), 8,91 (1H, user. C).

Stage 2

2-Benzyl 1-tert-butyl 5-bromo-1H-in the ol-1,2, in primary forms

Specified in the title compound (225 mg) was obtained in a way similar to stage 1 of example 35, using benzyl 5-bromo-1H-indole-2-carboxylate obtained in the above stage 1 (184 mg).

1H-NMR (CDCl3) δ: to 5.35 (2H, s), 7.03 is-7,05 (1H, m), 7,32-7,41 (3H, m), 7,41 was 7.45 (2H, m), 7,46-7,51 (1H, m), 7,70-7,73 (1H, m), 7,98-to 7.93 (1H, m).

Stage 3

2-Benzyl 1-tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1,2 -, in primary forms

Specified in the title compound (150 mg) was obtained in a way similar to stage 1 of example 27, using the compound obtained in the above stage 2 (220 mg).

1H-NMR (CDCl3) δ: 1,36 (13H, s)of 1.57 (9H, s), are 5.36 (2H, d, J=1,8 Hz), 7,14 (1H, d, J=1,8 Hz), 7,31-7,42 (3H, m), 7,45 (2H, d, J=7,3 Hz), to 7.84 (1H, d, J=8,3 Hz), with 8.05 (1H, d, J=8,3 Hz), 8,08 (1H, s).

Stage 4

Benzyl 5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-indole-2-carboxylate

Specified in the title compound (52 mg) was obtained in a way similar to stage 1 of example 3, using the compound obtained in the above stage 3 (150 mg)and the compound obtained in stage 1 of example 4 (98 mg).

MS (ESI) m/z: 483 (M+H)+.

HRMS (ESI) [M+H]+calculated: C28H27N4O4483,20323; found: 483,20082.

1H-NMR (DMSO-d6) δ: of 1.20 to 1.37 (2H, m), 1,42-and 1.54 (3H, m), 2.00 in and 2.14 (1H, m), 3,16-3,30 (2H, m), 3,76 (2H, d, J=7,3 Hz), 3,78-of 3.85 (2H, m), of 5.39 (2H, s), 7.24 to 7,27 (1H, m), 7,33 was 7.45 (3H, m), 7,47-7,52 (3H, m), 7,54 (1H, d, J=8.7 Hz), to 7.61 (1H, DD, J=8,7, 1.8 Hz), 7,82 (1H, d, J=2.3 Hz), 7,95 (1H, s), 8,19 (1H, d, J=1,8 Hz), to 11.56 (1H, user. C)12,00 (1H, user. C).

Stage 5

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-indole-2-carboxylic acid

Into a solution of the compound obtained in the above stage 4 (49 mg)in ethanol (6 ml) was added to a mixture of 4 G. hydrochloric acid and dioxane (1 ml) and 10% of the catalyst is palladium on coal (30 mg)and the mixture was stirred in an atmosphere of hydrogen for 21 hours. The catalyst was filtered. After washing with ethanol, the filtrate was concentrated under reduced pressure. The obtained residue was purified by thin-layer chromatography (elwira a mixture of methanol-water-chloroform) to obtain the specified title compound (39 mg).

MS (ESI) m/z: 393 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H21N4O4393,15628; found: 363,15310.

1H-NMR (DMSO-d6) δ: 1,19-to 1.38 (2H, m), 1,42-and 1.54 (2H, m), 1,99-to 2.15 (1H, m), 3,18-and 3.31 (2H, m), 3.72 points-3,86 (4H, m), of 6.71 (1H, s), of 7.36-7,47 (2H, m), 7,79-7,81 (2H, m), 8,17 (1H, s), br11.01 (1H, user. C)11,50 (1H, user. C).

(Example 81)

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-indole-3-carbaldehyde

Stage 1

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-3-carbaldehyde

Specified in the title compound (0.65 g) was obtained by the method similar to that applied to the and stage 1 of example 27, using 5-bromo-1H-indole-3-carbaldehyde (1.5 g).

MS (ESI) m/z: 272 (M+H)+.

1H-NMR (CDCl3) δ: 1,37 (11H, s), the 7.43 (1H, d, J=8,3 Hz), to 7.77 (1H, d, J=8,3 Hz), 7,86 (1H, d, J=2,8 Hz), 8,81 (1H, s), 8,83 (1H, user. C), 10,11 (1H, s).

Stage 2

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-indole-3-carbaldehyde

Specified in the title compound (128 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (150 mg)and the compound obtained in stage 1 of example 4 (173 mg).

HRMS (ESI) [M+H]+calculated: C21H21N4O3377,16136; found: 377,16065.

1H-NMR (DMSO-d6) δ: 1,19-1,32 (2H, m), 1.41 to 1,49 (2H, m), 1,98-2,11 (1H, m), 3,16-of 3.25 (2H, m), 3.95 to of 3.97 (4H, m), 7,56 (1H, DD, J=8,3, 2.0 Hz), a 7.62 (1H, d, J=8.6 Hz), to 7.77 (1H, d, J=1.7 Hz), 8,16 (1H, d, J=2.3 Hz), 8,27 (1H, s), 8,31-of 8.28 (1H, m), of 9.89 (1H, s).

(Example 82)

6-(1H-Pyrrolo[3,2-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Tert-butyl 5-chloro-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

Specified in the header connection (839 mg) was obtained in a way similar to stage 1 of example 35, using 5-chloro-1H-pyrrolo[3,2-b]pyridine (600 mg).

1H-NMR (CDCl3) δ: 1,68 (9H, s)of 6.71 (1H, DD, J=3,7, 0.6 Hz), 7,24 (1H, d, J=8.5 Hz), 7,83 (1H, d, J=3,7 Hz), 8,31-of 8.33 (1H, m).

Stage 2

3-Cyclohex-1-EN-1-yl-6-(1H-pyrrolo[3,2-b]PI is one-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (95 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (79 mg)and the compound obtained in stage 4 of example 35 (130 mg).

MS (ESI) m/z: 430 (M+H)+.

1H-NMR (CDCl3) δ: 1,45-and 1.54 (2H, m), 1,61 was 1.69 (2H, m), 1,73-to 1.82 (2H, m), 1,86-of 1.92 (2H, m), 2,15-of 2.28 (1H, m), 2,30-of 2.38 (2H, m), 2,46-of 2.54 (2H, m), 3,31-to 3.41 (2H, m), a 3.87 (2H, d, J=7,3 Hz), 3,93-was 4.02 (2H, m), 6,05-6,11 (1H, m), 6,85 (1H, s), 7,49-rate of 7.54 (1H, m), to 7.59 (1H, d, J=8.7 Hz), 7,79 (1H, d, J=8.7 Hz), of 8.04 (1H, d, J=1,8 Hz), with 8.33 (1H, user. C)8,59 (1H, d, J=1,8 Hz).

Stage 3

6-(1H-Pyrrolo[3,2-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (30 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (90 mg).

MS (ESI) m/z: 350 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N5O2350,16170; found: 350,16064.

1H-NMR (DMSO-d6) δ: 1,26-of 1.40 (2H, m), 1,47-of 1.57 (2H, m), 2,01-of 2.16 (1H, m), 3,20 to be 3.29 (2H, m), 3,76-3,88 (4H, m), 6,60-only 6.64 (1H, m), 7,66-of 7.69 (1H, m), 7,73 (1H, d, J=8.7 Hz), 7,86 (1H, d, J=8.7 Hz), to 8.12 (1H, d, J=1,8 Hz), 8,63 (1H, d, J=1,8 Hz), 11,35 (1H, user. C)are 11.62 (1H, user. C).

(Example 83)

6-(1H-Pyrrolo[2,3-c]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Tert-butyl 5-chloro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate

<> Specified in the header connection (811 mg) was obtained in a way similar to stage 1 of example 35, using 5-chloro-1H-pyrrolo[2,3-c]pyridine (583 mg).

1H-NMR (CDCl3) δ: 1.69 in (9H, s), 6,55 (1H, d, J=3,7 Hz), 7,50-7,51 (1H, m), to 7.77 for 7.78 (1H, m), 9,14 (1H, s).

Stage 2

3-Cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-c]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (79 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (85 mg)and the compound obtained in stage 4 of example 35 (140 mg).

MS (ESI) m/z: 430 (M+H)+.

1H-NMR (CDCl3) δ: 1,43-of 1.57 (4H, m), 1,73-of 1.81 (2H, m), 1,86-of 1.94 (2H, m), 2,13-of 2.27 (1H, m), 2,30-of 2.38 (2H, m), 2,47 is 2.55 (2H, m), 3,31-to 3.41 (2H, m), 3,85 (2H, d, J=7,3 Hz), 3,93-4,01 (2H, m), 6,06-6,10 (1H, m), to 6.67 (3H, d, J=3.2 Hz), was 7.45 (1H, d, J=3.2 Hz), 7,98-to 7.93 (2H, m), 8,61 (1H, d, J=1,8 Hz), 8,67 (1H, user. C)of 8.92 (1H, s).

Stage 3

6-(1H-Pyrrolo[2,3-c]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (58 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (78 mg).

MS (ESI) m/z: 350 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N5O2350,16170; found: 350,16216.

1H-NMR (DMSO-d6) δ: 1,22-of 1.39 (2H, m), 1,45 is 1.58 (2H, m), 2,02-of 2.16 (1H, m), 3,21-3,29 (2H, m), with 3.79 (2H, d, J=7,4 Hz), 3,81-a 3.87 (2H, m), 6,54 return of 6.58 (1H, m), 7,62-7,66 (1H, m)to 8.12 (1H, d, J=2,9 Hz), 8,15 (1H, s), 8,65 (1H, d, J=2.3 Hz), 8,84 (1H, s), 11,57 (1H, user. C)11,63 (1H, user. C).

(Example 84)

1-(Tetrahydro-2H-Piran-4-ylmethyl)-6-[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-1-[(4-were)sulfonyl]-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine

5-Bromo-3-iodine-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2006/015123 (240 mg)was dissolved in N,N-dimethylformamide (5 ml). Added copper iodide (96 mg) and methyl debtor(persulfonic)acetate (0,254 ml) and the mixture was stirred with heating at 80°C for 18 hours. The reaction solution was diluted with ethyl acetate and the insoluble substance was separated by filtration. The filtrate was washed with saturated brine, saturated aqueous sodium bicarbonate solution and again with saturated salt solution. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (140 mg).

MS (ESI) m/z: 419 (M+H)+.

1H-NMR (CDCl3) δ: 2,43 (3H, s), of 7.36 (2H, d, J=8.5 Hz), 8,13 (4H, m), 8,56 (1H, d, J=2.2 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-6-{1-[(4-were)sulfonyl]-3-(trifluoromethyl)-1H-feast of the olo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (74 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (122 mg)and the compound obtained in stage 4 of example 35 (120 mg).

MS (ESI) m/z: 652 (M+H)+.

1H-NMR (CDCl3) δ: 1,24 is 1.34 (2H, m), 1.41 to and 1.54 (2H, m), 1,72-of 1.81 (2H, m), 1,86-of 1.93 (3H, m), 2,07-2,22 (1H, m), 2,29-is 2.37 (2H, m), 2,42 (3H, s), 2,44-2,52 (2H, m), 3,31-to 3.41 (2H, m), 3,83 (2H, d, J=6.9 Hz), 3,93-a 4.03 (2H, m), 6,04-6,09 (1H, m), 7,27 (1H, d, J=2,8 Hz), was 7.36 (2H, d, J=8,3 Hz), 8,05-8,08 (1H, m), 8,20-8,15 (3H, m), by 8.22 (1H, d, J=2.3 Hz), 8,68 (1H, d, J=1,8 Hz).

Stage 3

3-Cyclohex-1-EN-1-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-6-[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 2 (72 mg)in tetrahydrofuran (1 ml) was added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (280 μl) and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure. The obtained residue was purified by thin-layer chromatography (elwira a mixture of methanol-dichloromethane) to obtain the specified title compound (29 mg).

MS (ESI) m/z: 498 (M+H)+.

1H-NMR (CDCl3) δ: 1,46-of 1.55 (2H, m), 1,60 was 1.69 (2H, m), 1,74-to 1.82 (2H, m), 1,87 is 1.96 (2H, m), 2,11-of 2.26 (1H, m), 2,30-2,39 (2H, m), 2,46-of 2.54 (2H, m), 3,37 (2H, t, J=11.2 Hz), 3,85 (2H, d, J=7,3 Hz), 3.95 to a 4.03 (2H, m), between 6.08 (1H, s), 7,34-7,38 (1H, m), of 7.75 (1H, s), 8,18 (1H, s), compared to 8.26-8.30 to (1H, m), 57-8,61 (1H, m), to 9.32 (1H, user. C).

Stage 4

1-(Tetrahydro-2H-Piran-4-ylmethyl)-6-[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (19 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (28 mg).

MS (ESI) m/z: 418 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H19F3N5O2418,14908; found: 418,14801.

1H-NMR (DMSO-d6) δ: 1,22-of 1.39 (2H, m), 1,45-1,55 (2H, m), 2,03-to 2.18 (1H, m), 3,19-3,29 (2H, m), 3,74-3,86 (4H, m), 7,95 (1H, d, J=1,8 Hz), 8,21-of 8.25 (2H, m), compared to 8.26 (1H, d, J=1,8 Hz), 8,71 (1H, d, J=1,8 Hz), 11,66 (1H, user. C).

(Example 85)

6-(3-Acetyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

1-(5-Bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)alanon

To a solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine (250 mg) in dichloromethane (5 ml) at room temperature for 10 minutes was added trichloride aluminum (846 mg). Then was added acetyl chloride (135 μl) and the mixture was stirred at room temperature for 5 hours. The reaction solution was poured into ice-cold water and were separated by addition of dichloromethane. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. Receiving the hydrated residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (186 mg).

MS (ESI) m/z: 239 (M+H)+.

1H-NMR (CDCl3) δ: to 2.55 (3H, s), 7,98 (1H, d, J=2,8 Hz), to 8.45 (1H, d, J=2.3 Hz), cent to 8.85 (1H, d, J=1,8 Hz), 10,28 (1H, user. C).

Stage 2

6-(3-Acetyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (26 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (65 mg)and the compound obtained in stage 4 of example 35 (113 mg).

MS (ESI) m/z: 472 (M+H)+.

1H-NMR (CDCl3) δ: 1,43-and 1.54 (2H, m), 1,61 is 1.70 (2H, m), 1,74 of-1.83 (2H, m), 1,86 is 1.96 (2H, m), 2,11-of 2.25 (1H, m), 2,31-of 2.38 (2H, m), 2,47-of 2.54 (2H, m), 2,59 (3H, d, J=2,8 Hz), 3,32-of 3.43 (2H, m), 3,82-to 3.89 (2H, m), 3,94-4,04 (2H, m), 6,05-6,12 (1H, m), 7,41 (1H, d, J=1,8 Hz), 8,01-of 8.06 (1H, m), 8,29-of 8.33 (1H, m), 8,59 (1H, s), 8,84-8,88 (1H, m), 9,63 (1H, user. C).

Stage 3

6-(3-Acetyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (5 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (25 mg).

MS (ESI) m/z: 392 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H22N5O3392,17226; found: 392,17437.

1H-NMR (DMSO-d6) δ: 1,27-to 1.38 (2H, m), 1,46-of 1.55 (2H, m), 2,03-2,17 (1H, m), 3,19 of 3.28 (2H, m), with 3.79 (2H, d, J=7,4 Hz), 3,80-3,86 (2H, m), 7,74 (1H, d, J=2,9 Hz), of 7.97 (1H, d, J=1.7 Hz), 8,18 (1H, d, J=1.7 Hz), of 8.28 (1H, d, J=17 Hz), 8,65 (1H, d, J=2.3 Hz), 11,63 (1H, user. C)12,09 (1H, user. C).

(Example 86)

6-[2-(Ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-3-(3-{[tert-butyl(dimethyl)silyl]oxy}prop-1-Jn-1-yl)pyridine-2-amine

In the solution of the dichloride bis(triphenylphosphine)palladium(II) (105 mg) in triethylamine (10.4 ml) was added copper iodide (57 mg) and the mixture was heated under reflux for 15 minutes. The reaction solution was cooled to 40°C. was Added tert-butyl(dimethyl)(propyne-2-in-1 yloxy)silane (752 mg) and then 5-bromo-3-yodellin-2-amine (896 mg) and the mixture was stirred at the same temperature for one hour. The solvent was evaporated under reduced pressure and the obtained residue was separated by adding ethyl acetate and distilled water. The obtained organic layer is washed with 10% aqueous citric acid solution and saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (606 mg).

MS (ESI) m/z: 341 (M+H)+.

1H-NMR (CDCl3) δ: 0,16 (6H, s)of 0.93 (9H, s), 4,56 (2H, s)5,00 (2H, user. C)to 7.59 (1H, d, J=2.3 Hz), with 8.05 (1H, d, J=2.3 Hz).

Stage 2

6-[2-({[Tert-butyl(dimethyl)silyl]the XI}methyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-3-cyclohex-1-EN-1-yl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (64 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (114 mg)and the compound obtained in stage 4 of example 35 (140 mg).

MS (ESI) m/z 574 (M+H)+.

1H-NMR (CDCl3) δ: 0,15 (6H, s)to 0.96 (9H, s), 1,44 was 1.69 (4H, m), 1,74 of-1.83 (2H, m), 1,86 is 1.96 (2H, m), 2,11-of 2.25 (1H, m), 2,30-2,39 (2H, m), 2,45-of 2.54 (2H, m), 3,31-of 3.42 (2H, m), a-3.84 (2H, d, J=7,3 Hz), 3.95 to Android 4.04 (2H, m), 4,94 (2H, s), 6,04-6,10 (1H, m), 6,33-6,36 (1H, m), of 7.36 (1H, d, J=1,8 Hz), 7,98 (1H, d, J=1,8 Hz), of 8.28 (1H, d, J=1,8 Hz), 8,43 (1H, d, J=2.3 Hz), of 8.90 (1H, user. C).

Stage 3

6-[2-(Ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (9 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (61 mg).

HRMS (ESI) [M+H]+calculated: C22H26N5O3408,20356; found: 408,20579.

1H-NMR (CDCl3) δ: 1,24 to 1.31 (3H, m), 1,45-and 1.54 (2H, m), 1,61 by 1.68 (2H, m), 3,32-of 3.42 (2H, m), 3,57-3,66 (2H, m), 3,82 (2H, d, J=7,3 Hz), 3,94-a 4.03 (2H, m), 4.72 in (2H, s), 6,44 (1H, s), 7,34-7,39 (1H, m), 8,00-8,02 (1H, m), 8,24 compared to 8.26 (1H, m), 8,44-of 8.47 (1H, m), 8,99 (1H, user. C).

(Example 87)

6-(2,3-Dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-2,3-dimethyl-1H-pyrrolo[2,3-b]pyridine

To a solution of 5-bromo-2-guide is azidopyridine (1000 mg) in ethanol (10 ml) was added 2-butanone (715 μl) and the mixture was heated under reflux for 2 hours. The reaction solution was concentrated under reduced pressure. Added diethylene glycol (10 ml) and the mixture was heated under reflux for 23 hours. The reaction solution was concentrated under reduced pressure and separated by adding dichloromethane and distilled water. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (104 mg).

1H-NMR (CDCl3) δ: 2,17 (3H, s), is 2.40 (3H, s), a 7.85 (1H, d, J=1,8 Hz), to 8.20 (1H, d, J=1,8 Hz), 8,69 (1H, user. C).

Stage 2

3-Cyclohex-1-EN-1-yl-6-(2,3-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (37 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (75 mg)and the compound obtained in stage 4 of example 35 (140 mg).

MS (ESI) m/z: 458 (M+H)+.

1H-NMR (CDCl3) δ: 1,42 is 1.58 (2H, m), 1,73-to 1.82 (2H, m), 1.85 to 1,99 (4H, m), 2,10-of 2.24 (1H, m), and 2.27 (3H, s), 2,31-of 2.38 (2H, m), is 2.44 (3H, s), 2,46-of 2.54 (2H, m), 3,31-of 3.42 (2H, m), a-3.84 (2H, d, J=6.4 Hz), 3,93-a 4.03 (2H, m), 6,04-6,11 (1H, m), 7,34-7,38 (1H, m), a 7.85 (1H, s), compared to 8.26-8.30 to (1H, m), 8,33-at 8.36 (1H, m), 8,54 (1H, user. C).

Stadia

6-(2,3-Dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (17 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (37 mg).

MS (ESI) m/z: 378 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H24N5O2378,19300; found: 378,19290.

1H-NMR (DMSO-d6) δ: 1,22-to 1.38 (2H, m), 1,46-of 1.55 (2H, m), 2,04-to 2.15 (1H, m), 2,22 (3H, s), of 2.34 (3H, s), 3,20 to be 3.29 (2H, m), of 3.78 (2H, d, J=7,4 Hz), 3,80-3,86 (2H, m), 7,89 (1H, d, J=1.7 Hz), 8,03 (1H, d, J=2.3 Hz), 8,23 (1H, d, J=1.7 Hz), 8,40 (1H, d, J=1.7 Hz), of 11.29 (1H, s), 11,57 (1H, user. C).

(Example 88)

6-(1H-Pyrrolo[3,2-b]pyridine-6-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (33 mg) was obtained in a way similar to stage 3 of example 1, using 6-bromo-1H-pyrrolo[3,2-b]pyridine (100 mg) and the compound obtained in stage 1 of example 77 (118 mg).

MS (ESI) m/z: 350 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H19N5O2350,16170; found: 350,1628.

1H-NMR (DMSO-d6) δ: 1,21-of 1.39 (2H, m), 1,47-of 1.55 (2H, m), 2,03-2,17 (1H, m), 3,19-3,29 (2H, m), of 3.78 (2H, d, J=7,3 Hz), 3,80-a 3.87 (2H, m), is 6.61 (1H, s), 7.68 per-7,72 (1H, m), 7,94 (1H, d, J=1,8 Hz), 8,01-with 8.05 (1H, m), compared to 8.26 (1H, d, J=1,8 Hz), 8,67 (1H, d, J=1,8 Hz), 11,46 (1H, user. C)11,64 (1H, user. C).

(Example 89)

6-{3-[(Dimethylamino)methyl]-1H-p is Rolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (100 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (200 mg)and 5-bromo-1H-pyrrolo[2,3-b]pyridine (89 mg).

MS (ESI) m/z: 430 (M+H)+.

Stage 2

3-Cyclohex-1-EN-1-yl-6-{3-[(dimethylamino)methyl]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

In the solution dimethylaminohydrolase (40 mg) in acetic acid (0.5 ml) under ice cooling was added formalin (34 μl) and the mixture was stirred at the same temperature for 10 minutes. After heating to room temperature was added 3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he obtained in the above stage 1 (100 mg)and the mixture was stirred at the same temperature for 16 hours. Acetic acid is kept under reduced pressure and added water, then was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloro who Orme) to obtain the specified title compound (102 mg).

MS (ESI) m/z: 487 (M+H)+.

Stage 3

6-{3-[(Dimethylamino)methyl]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (48 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (102 mg).

MS (ESI) m/z: 407 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C22H27N6O2407,21955; found: 407,21458.

1H-NMR (DMSO-d6) δ: 1,28-of 1.36 (2H, m)and 1.51 (2H, d, J=10,9 Hz), 2,08-2,12 (1H, m)to 2.18 (6H, s), 3,24 (2H, t, J=10,9 Hz), 3,61 (2H, s), 3,78-a-3.84 (4H, m), 7,40-7,42 (1H, m), 7,88-7,89 (1H, m), 8,20-8,21 (1H, m), by 8.22-8,23 (1H, m), charged 8.52-8,53 (1H, m), 11,59 (1H, user. C)to 11.61 (1H, user. C).

(Example 90)

6-{3-Isopropyl-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-3-Isopropenyl-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine

5-Bromo-3-iodine-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2006/015123 (150 mg), was dissolved in a mixed solvent of acetonitrile (1.5 ml) and aqueous sodium carbonate solution (2 M, 1.5 ml). Added pinacolone ether Isopropenyl-Bronevoy acid (0,071 ml) and dichloride bis(triphenylphosphine)palladium(II) (11 mg) and the mixture was heated with stirring at 60°C overnight and at 80°C for 7 hours in a nitrogen atmosphere is hermetically closed vessel. The reaction solution was cooled to room temperature, diluted with ethyl acetate and washed with saturated saline solution. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The obtained residue was purified by thin-layer chromatography (elwira a mixture of toluene) to obtain specified in the title compound (53 mg).

MS (ESI) m/z: 391 (M+H)+.

1H-NMR (CDCl3) δ: 2,15-of 2.16 (3H, m), of 2.38 (3H, s), to 5.21-5,24 (1H, m), 5.40 to-5,42 (1H, m), 7,29 (2H, d, J=8.1 Hz), 7,71 (1H, s), with 8.05 (2H, d, J=8.1 Hz), by 8.22 (1H, d, J=2.2 Hz), 8,44 (1H, d, J=2.2 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-6-{3-Isopropenyl-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (102 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (100 mg)and the compound obtained in the above stage 1 (88 mg).

MS (ESI) m/z: 624 (M+H)+.

Stage 3

3-Cyclohex-1-EN-1-yl-6-{3-Isopropenyl-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (50 mg) was obtained in a way similar to stage 3 of example 84 using the compound obtained in the above stage 2 (102 mg).

MS (ESI) m/z: 470 (M+H)+.

Stage 4

6-{3-Isopropyl-1H-PI is Rolo[2,3-b]pyridine-5-yl}-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (8 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (50 mg).

MS (ESI) m/z: 392 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C22H26N5O2392,20865; found: 392,20520.

1H-NMR (CDCl3) δ: of 1.41 (3H, s)of 1.42 (3H, s), 1,46-of 1.57 (2H, m), 1,64-1,71 (2H, m), 2,16-of 2.26 (1H, m), 3,23-3,30 (1H, m), 3,35-to 3.41 (2H, m), a 3.87 (2H, d, J=7,3 Hz), 3,98-was 4.02 (2H, m), 7,19-7,20 (1H, m), 7,41-7,42 (1H, m), 8,11 (1H, d, J=1,8 Hz), 8,32 (1H, d, J=1,8 Hz), 8,53 (1H, d, J=1,8 Hz), RS 9.69 (1H, user. C)10,80 (1H, user. C).

(Example 91)

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

Stage 1

2-Amino-5-bromo-3-edisonnation.com

Specified in the header connection (vs. 5.47 g) was obtained by the method similar to those used in stage 1 of example 36 using 2-amino-5-bromo-isonicotinamide obtained by the method described in WO 2007/113226 (5,00 g).

MS (ESI) m/z: 324 (M+H)+.

Stage 2

2-Amino-5-bromo-3-[(trimethylsilyl)ethinyl]isonicotinamide

Specified in the header connection (1,38 g) was obtained in a way similar to step 2 of example 36, using the compound obtained in the above stage 1 (3.00 g).

MS (ESI) m/z: 294 (M+H)+.

Stage 3

N-{5-Bromo-4-cyano-3-[(trimethylsilyl)ethinyl]pyridine-2-yl}ndimethylacetamide

The decree is Noah in the title compound (646 mg) was obtained by way similar to the one used in stage 4 of example 78, using the compound obtained in the above stage 2 (1,33 g).

MS (ESI) m/z: 336 (M+H)+.

Stage 4

5-Bromo-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

Specified in the title compound (78 mg) was obtained in a way similar to stage 5 of example 78, using the compound obtained in the above stage 3 (646 mg).

MS (ESI) m/z: 222 (M+H)+.

1H-NMR (DMSO-d6) δ: of 6.65 (1H, d, J=3.5 Hz), of 7.90 (1H, d, J=3.5 Hz), 8,55 (1H, s).

Stage 5

Tert-butyl 5-bromo-4-cyano-1H-pyrrolo[2,3-b]pyridine-carboxylate

Specified in the title compound (108 mg) was obtained in a way similar to stage 1 of example 35 using the compound obtained in the above stage 4 (78 mg).

MS (ESI) m/z: 266 (M-tBu+H)+.

Stage 6

5-[3-Cyclohex-1-EN-1-yl-2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

Specified in the title compound (125 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (163 mg)and the compound obtained in the above stage 5 (108 mg).

MS (ESI) m/z: 455 (M+H)+.

Stage 7

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

Specified in the header of the compounds is their (54 mg) was obtained by way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (125 mg).

MS (ESI) m/z: 375 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C20H19N6O2375,15695; found: 375,15940.

1H-NMR (DMSO-d6) δ: of 1.30 and 1.33 (2H, m), 1,48-of 1.52 (2H, m), 2.05 is-a 2.12 (1H, m), up 3.22 (2H, t, J=11.2 Hz), 3.72 points of 3.75 (2H, m), 3,79-a 3.83 (2H, m), 6,67-6,69 (1H, m), 7,88-of 7.90 (2H, m), 8,15-8,17 (1H, m), 8,51-charged 8.52 (1H, m), to 11.79 (1H, user. C), 12,46 (1H, user. C).

(Example 92)

Ethyl 5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

Stage 1

5-Bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

To a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde obtained by the method described in WO 2004/101565 (150 mg), in methanol (1.0 ml) under nitrogen atmosphere was added gidroxinimesoulid (46 mg) and the mixture was stirred at room temperature for one hour. After azeotropic distillation with toluene, the suspension of the residue in toluene (2 ml) was added thionyl chloride (118 μl)and the mixture was stirred at 80°C for 16 hours and at 100°C for 8 hours. After cooling to room temperature was added a saturated aqueous solution of sodium bicarbonate, then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. Received the initial residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (88 mg).

MS (ESI) m/z: 222 (M+H)+.

1H-NMR (DMSO-d6) δ: scored 8.38 is 8.38 (1H, m), of 8.47-of 8.47 (1H, m), and 8.50 (1H, s).

Stage 2

Tert-butyl 5-bromo-3-cyano-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

Specified in the title compound (91 mg) was obtained in a way similar to stage 1 of example 35 using the compound obtained in the above stage 1 (88 mg).

MS (ESI) m/z: 266 (M-tBu+H)+.

Stage 3

5-[3-Cyclohex-1-EN-1-yl-2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Specified in the title compound (77 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (138 mg), and the compound obtained in the above stage 2 (91 mg).

MS (ESI) m/z: 455 (M+H)+.

Stage 4

Ethyl 5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

Specified in the title compound (37 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (75 mg).

MS (ESI) m/z: 422 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C22H24N5O4422,18283; found: 422,18716.

1H-NMR (DMSO-d6) δ: of 1.29 to 1.37 (5H, m), 1,50 (2H, d, J=10,9 Hz), 2.06 to 2,11 (1H, m), up 3.22 (2H, t, J=10,9 Hz), of 3.77-a 3.83 (4H, m), or 4.31 (2H, q, J=7,1 Hz), 7,92 (1H, d, J=1 Hz), 8,21 (1H, d, J=1.7 Hz), compared to 8.26 (1H, s), 8,49 (1H, d, J=2.3 Hz), 8,63 (1H, d, J=2.3 Hz), 11,65 (1H, user. C).

(Example 93)

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid

Stage 1

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid

The aqueous layer was in the process of separation in stage 4 of example 92 was concentrated and purified by thin-layer chromatography (elwira a mixture of methanol-water-chloroform) to obtain the specified title compound (14 mg).

MS (ESI) m/z: 394 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C20H20N5O4394,15153; found: 394,15466.

1H-NMR (DMSO-d6) δ: 1,27-of 1.35 (2H, m), for 1.49 (2H, d, J=11.5 Hz), 2.05 is-a 2.12 (1H, m), 3,19-of 3.25 (1H, m), of 3.77-a 3.83 (4H, m), to $ 7.91 (1H, d, J=1.7 Hz), 8,16 (1H, s), 8,19 (1H, d, J=1.7 Hz), 8,49-and 8.50 (1H, m), 8,59 at 8.60 (1H, m), 11,63 (1H, user. C), 12,48 (1H, user. C).

(Example 94)

N-Methyl-5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide

Stage 1

N-Methyl-5-[2-oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide

The compound obtained in stage 4 of example 92 (34 mg), was dissolved in a solution of methylamine in methanol (1 M, 20 ml) and the solution was stirred germ is almost a closed vessel at 100°C for 16 hours. The solvent was evaporated under reduced pressure. The residue was again dissolved in a solution of methylamine in methanol (1 M, 20 ml) and the solution was stirred in a sealed vessel at 120°C for 23 hours. After cooling to room temperature the solvent was concentrated under reduced pressure and the residue was purified by thin-layer chromatography (elwira a mixture of methanol-chloroform) to obtain the specified title compound (14 mg).

MS (ESI) m/z: 407 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C21H23N6O3407,18316; found: 407,18633.

1H-NMR (DMSO-d6) δ: 1,28-to 1.38 (2H, m), 1,48-of 1.55 (2H, m), 2,07 with 2.14 (1H, m), 2,82 (3H, s)of 3.25 (2H, t, J=12.0 Hz), 3,79-of 3.85 (4H, m), to $ 7.91 (1H, s), 8,08 (1H, user. C), 8,13 (1H, s), 8,24 (1H, s), at 8.60 (1H, s), 8,68 (1H, s), of 11.69 (1H, user. C), 12,21 (1H, user. C).

(Example 95)

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Stage 1

5-[2-Oxo-1-(tetrahydro-2H-Piran-4-ylmethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl]-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Specified in the title compound (62 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 77 (112 mg)and the compound obtained in stage 1 of example 92 (75 mg).

MS (ESI) m/z: 375 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C20H9 FN6O2375,15695; found: 375,15878.

1H-NMR (DMSO-d6) δ: of 1.28 to 1.37 (2H, m)and 1.51 (2H, d, J=10.3 Hz), 2,08 with 2.14 (1H, m), 3,24 (2H, t, J=10,6 Hz), with 3.79 (2H, d, J=7,4 Hz), 3,81-of 3.85 (2H, m), 7,80 (1H, user. C)8,01 (1H, d, J=2.3 Hz), with 8.33 (1H, d, J=2.3 Hz), 8,40 (1H, d, J=2.3 Hz), 8,51 (1H, s), is 8.75 (1H, d, J=2.3 Hz), 11,66 (1H, user. C).

(Example 96)

6-(3-Fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Tert-butyl 5-bromo-3-fluoro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Specified in the title compound (0.52 g) was obtained by the method similar to those used in stage 1 of example 35, using 5-bromo-3-fluoro-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2009/016460 (1.2 g).

1H-NMR (CDCl3) δ: of 1.66 (9H, s), 7,42 (1H, d, J=2.0 Hz), of 8.06 (1H, d, J=2.0 Hz), to 8.57 (1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (104 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 4 of example 35 (192 mg)and the compound obtained in the above stage 1 (125 mg).

MS (ESI) m/z: 448 (M+H)+.

Stage 3

6-(3-Fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (60 mg) recip is there any way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (104 mg).

MS (ESI) m/z: 368 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C19H18FN5O2368,15228; found: 368,15682.

1H-NMR (DMSO-d6) δ: of 1.28 to 1.37 (2H, m), 1,49-of 1.52 (2H, m), 2,07 with 2.14 (1H, m), 3,24 (2H, t, J=11.2 Hz), of 3.77 (2H, d, J=6.9 Hz), 3,81-of 3.85 (2H, m), 7,52-rate of 7.54 (1H, m), of 7.97 (1H, s), 8,29-8,30 (2H, m), 8,63 (1H, d, J=1.7 Hz), 11,59 (1H, user. C)are 11.62 (1H, user. C).

(Example 97)

1-[(1,1-Dissidocerida-2H-thiopyran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(1,1-dissidocerida-2H-thiopyran-4-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (313 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg), and (1,1-dissidocerida-2H-thiopyran-4-yl)methanol obtained by the method described in US 2007/82931 (187 mg).

MS (APCI) m/z: 440 [M+H]+.

1H-NMR (CDCl3) δ: 1,71-of 1.78 (2H, m), 1,83-1,90 (2H, m), 1,96-of 2.20 (5H, m), 2,28-of 2.34 (2H, m), 2,38 is 2.44 (2H, m), of 2.97 (2H, DD, J=17,9, and 8.7 Hz), 3,11 (2H, d, J=13,4 Hz), of 3.78 (2H, d, J=6.8 Hz), 6,00-of 6.02 (1H, m), 7,28 (1H, d, J=2.0 Hz), to 8.12 (1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(1,1-dissidocerida-2H-thiopyran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in is the head of the compound (91 mg) was obtained by way similar to the one used in stage 3 of example 1 using the compound obtained in the above stage 1 (309 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 478 [M+H]+.

Stage 3

1-[(1,1-Dissidocerida-2H-thiopyran-4-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (63 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (91 mg).

MS (APCI) m/z: 398 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,72-of 1.84 (2H, m), 1,97 is 2.00 (2H, user. m), 2.21 are of 2.23 (1H, user. m)3,09-3,11 (4H, m), 3,83 (2H, d, J=7,1 Hz), of 6.52 (1H, DD, J=3.1 and 1.9 Hz), 7,53 (1H, t, J=3.1 Hz), 7,95 (1H, d, J=1.9 Hz), 8,24-of 8.28 (2H, m), 8,56 (1H, d, J=1.9 Hz), 11,64 (1H, user. C)of 11.75 (1H, user. C).

(Example 98)

1-[(TRANS-4-Methoxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

(TRANS-4-Methoxycyclohexyl)methanol

(CIS-4-Methoxycyclohexyl)methanol

Specified in the title compound, TRANS-isomer (0,59 g) and CIS-isomer (0,94 g) was obtained in a way similar to step 2 of example 33, using 4-methoxycyclohexanone acid (2.0 g).

the TRANS-isomer

1H-NMR (CDCl3) δ: 0,98-1,02 (2H, m), 1,15-1,25 (2H, m), 1,44 of 1.50 (1H, m), 1,83-to 1.87 (2H, m), of 2.08 and 2.13 (2H, m), 3,07-of 3.12 (1H, m)to 3.35 (3H, s), of 3.46 (2H, d, J=,3 Hz).

CIS-isomer

1H-NMR (CDCl3) δ: 1.32 to 1.55V (7H, m), 1,88-of 1.92 (2H, m), and 3.31 (3H, s), 3.43-3.45 points (1H, m), 3,47-of 3.48 (2H, m).

Stage 2

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(TRANS-4-methoxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (216 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg), and (TRANS-4-methoxycyclohexyl)methanol obtained in the above stage 1 (164 mg).

MS (APCI) m/z: 420 [M+H]+.

1H-NMR (CDCl3) δ: 1,10-1,23 (5H, m), 1,73-1,88 (7H, m), 2,08-2,11 (2H, m), 2,30-2,31 (2H, m), 2,42 is 2.43 (2H, m)to 3.34 (3H, s), 3,68 (2H, d, J=7,1 Hz), 6,00-of 6.02 (1H, m), 7,27 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=2.0 Hz).

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(TRANS-4-methoxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (223 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (205 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (131 mg).

MS (APCI) m/z: 458 [M+H]+.

Stage 4

1-[(TRANS-4-Methoxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (141 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained by you is ukazannoi stage 3 (223 mg).

MS (APCI) m/z: 378 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,08-1,14 (5H, m), 1,66 by 1.68 (2H, m), 1,81-of 1.84 (1H, m), 1,97 of 1.99 (2H, m), 3,19 (3H, s), 3.72 points-3,74 (3H, m), of 6.52 (1H, DD, J=2,8, 1.9 Hz), 7,53 (1H, t, J=2,8 Hz), 7,86 (1H, d, J=1.9 Hz), 8,24 (2H, t, J=2.3 Hz), 8,55 (1H, d, J=2.3 Hz), 11,58 (1H, user. C)11,74 (1H, user. C).

(Example 99)

1-[(CIS-4-Methoxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(CIS-4-methoxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (298 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg)and the compound obtained in stage 1 of example 98 (164 mg).

MS (APCI) m/z: 420 [M+H]+.

1H-NMR (CDCl3) δ: 1,33 of 1.46 (6H, m), 1,73-to 1.77 (2H, m), 1,86-of 1.93 (5H, m), 2,30-2,31 (2H, m), 2,42-to 2.42 (2H, m), and 3.31 (3H, s), 3.43 points-of 3.46 (1H, user. m), 3,68 (2H, d, J=7,3 Hz), 6,00-of 6.02 (1H, m), 7,28 (1H, d, J=2.0 Hz), 8,07 (1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(CIS-4-methoxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (208 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (191 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 458 [M+H]+.

tadia 3

1-[(CIS-4-Methoxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (135 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (208 mg).

MS (APCI) m/z: 378 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,40-of 1.92 (10H, m), 3,18 (4H, s), of 3.73 (3H, d, J=7,1 Hz), 6,51 (1H, DD, J=3.3, which is 1.8 Hz), 7,52 (1H, t, J=2,8 Hz), 7,88 (1H, d, J=1,8 Hz), 8,24 (2H, DD, J=4,1, 2,1 Hz), 8,54 (1H, d, J=2.1 Hz), 11,57 (1H, user. C)11,73 (1H, user. C).

(Example 100)

4-{[2-Oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]methyl}tetrahydro-2H-Piran-4-carbonitril

Stage 1

4-[(6-Bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)methyl]tetrahydro-2H-Piran-4-carbonitril

Specified in the title compound (39 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg), and (4 cyanoacrylate-2H-Piran-4-yl)methanol obtained by the method described in WO 2008/029825 (161 mg).

MS (APCI) m/z: 417 [M+H]+.

Stage 2

4-{[3-Cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]methyl}tetrahydro-2H-Piran-4-carbonitril

Specified in the title compound (39 mg) was obtained in a way similar to stage 3 of example 1, using the the group obtained in the above stage 1 (39 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (25 mg).

MS (APCI) m/z: 455 [M+H]+.

Stage 3

4-{[2-Oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]methyl}tetrahydro-2H-Piran-4-carbonitril

Specified in the title compound (15 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (39 mg).

MS (APCI) m/z: 375 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,85-of 1.95 (4H, m), of 3.46 (2H, t, J=12.0 Hz), 3,92-of 3.94 (2H, user. m), 4,22 (2H, s), of 6.52 (1H, DD, J=3.3, which is 1.6 Hz), 7,53 (1H, DD, J=2.2, while the 1.6 Hz), 8,11 (1H, d, J=2.0 Hz), 8,21 (1H, d, J=2.2 Hz), of 8.28 (1H, d, J=1.6 Hz), 8,53 (1H, d, J=2.0 Hz), 11,76 (2H, user. C).

(Example 101)

1-[(TRANS-4-Hydroxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

TRANS-ethyl 4-{[Tert-butyl(dimethyl)silyl]oxy}cyclohexanecarboxylate

CIS-ethyl 4-{[Tert-butyl(dimethyl)silyl]oxy}cyclohexanecarboxylate

Specified in the title compound, TRANS-isomer (0.85 grams) and CIS-isomer (1.0 g), obtained in a way similar to step 2 of example 62, using ethyl 4-hydroxycyclohexanecarboxylate (2.0 g).

the TRANS-isomer

1H-NMR (CDCl3) δ: of 0.05 (6H, s)to 0.88 (9H, s)of 1.24 (3H, t, J=7,1 Hz), 1.30 and 1.32 to (2H, m), 1,46-1,49 (2H, m), 1,89 is 1.96 (4H, m), 2.21 are of 2.23 (1H, m), 3,55-to 3.58 (1H, m), 4,11 (2H, q, J=7,1 is C).

CIS-isomer

1H-NMR (CDCl3) δ: 0,03 (6H, s)to 0.89 (9H, s), 1,25 (3H, t, J=7,1 Hz), 1,49 of 1.50 (2H, m), 1,61-of 1.66 (4H, m), 1,92-of 1.95 (2H, m), 2,27-of 2.30 (1H, m), 3,88-are 3.90 (1H, m), of 4.12 (2H, q, J=7,1 Hz).

Stage 2

(TRANS-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)methanol

Specified in the header connection (0,83 g) was obtained in a way similar to step 2 of example 33, using TRANS-ethyl 4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanecarboxylate obtained in the above stage 1 (0.85 grams).

1H-NMR (CDCl3) δ: 0,06 (6H, s)to 0.89 (9H, s)of 0.97 to 1.00 (2H, m), 1,27-1,32 (2H, m), of 1.45 to 1.47 (1H, m), 1,78-of 1.81 (2H, m), 1,87 is 1.91 (2H, m), of 3.45 (2H, d, J=6.3 Hz), 3,51-of 3.54 (1H, m).

Stage 3

6-Bromo-1-[(TRANS-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)methyl]-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (273 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg)and the compound obtained in the above stage 2 (279 mg).

MS (APCI) m/z: 520 [M+H]+.

Stage 4

1-[(TRANS-4-{[tert-Butyl(dimethyl)silyl]oxy}cyclohexyl)methyl]-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (205 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (208 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 558 [M+H]+.

Stage 5

1-[(TRANS-4-Hydroxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (96 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (205 mg).

MS (APCI) m/z: 364 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,06-1,14 (5H, m), 1.60-to and 1.63 (2H, user. m), 1,81-to 1.87 (3H, user. m)to 3.73 (2H, d, J=10,2 Hz), 4,49 (1H, d, J=4.4 Hz), of 6.52 (1H, DD, J=3.3, which is 1.7 Hz), 7,53 (1H, DD, J=2,9) and 1.7 Hz), 7,86 (1H, d, J=1.7 Hz), 8,24 (2H, DD, J=2,9, 2.0 Hz), 8,55 (1H, d, J=2.0 Hz), 11,58 (1H, user. C)11,74 (1H, user. C).

(Example 102)

1-[(CIS-4-Hydroxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

(CIS-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)methanol

Specified in the header connection (0,89 g) was obtained in a way similar to step 2 of example 33, using CIS-ethyl 4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanecarboxylate obtained in stage 1 of example 101 (1.0 g).

1H-NMR (CDCl3) δ: 0,03 (6H, s)to 0.89 (9H, s), 1,26-of 1.29 (1H, m)of 1.46 to 1.48 (6H, m), 1,65-of 1.66 (2H, m), 3.46 in-3,49 (2H, m), 3.96 points-of 3.97 (1H, m).

Stage 2

6-Bromo-1-[(CIS-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)methyl]-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (251 mg) was obtained method is m, similar to the one used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg)and the compound obtained in the above stage 1 (279 mg).

MS (APCI) m/z: 520 [M+H]+.

Stage 3

1-[(CIS-4-{[tert-Butyl(dimethyl)silyl]oxy}cyclohexyl)methyl]-3-cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (194 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (208 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 558 [M+H]+.

Stage 4

1-[(CIS-4-Hydroxycyclohexyl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (92 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (194 mg).

MS (APCI) m/z: 364 [M+H]+.

1H-NMR (DMSO-d6) δ: 1.30 and to 1.98 (6H, m), of 3.73-3,81 (3H, m), the 4.29 (1H, d, J=3.2 Hz), 6,51-of 6.52 (1H, m), 7,52 (1H, DD, J=2,8, and 1.6 Hz), 7,87 (1H, d, J=6.8 Hz), 8,23 compared to 8.26 (2H, m), 8,54 (1H, d, J=2.0 Hz), 11,58 (1H, user. C)11,73 (1H, user. C).

(Example 103)

1-[(4,4-Diverticulosis)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

(4,4-Diverticulosis)methanol

Pointed to by the e in the title compound (0,423 g) was obtained by way similar to the one used in stage 2 of example 33, using ethyl 4,4-diverticulopexia (1.13 g).

1H-NMR (CDCl3) δ: of 1.29 and 1.33 (2H, m), 1.56 to was 1.58 (1H, m), 1,63 and 1.80 (2H, m), 1,84 is 1.86 (2H, m), 2,09 with 2.14 (2H, m), 3,52 (2H, d, J=6,6 Hz).

Stage 2

6-Bromo-3-cyclohex-1-EN-1-yl-1-[(4,4-diverticulosis)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (236 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg), and (4,4-diverticulosis)methanol obtained in the above stage 1 (171 mg).

MS (APCI) m/z: 426 [M+H]+.

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(4,4-diverticulosis)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (108 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (171 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 464 [M+H]+.

Stage 4

1-[(4,4-Diverticulosis)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (86 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (108 mg).

MS (APCI) m/z: 384 [M+H]+.

1H is the Mr (DMSO-d 6) δ: 1,26-of 1.40 (2H, m), 1,66-of 1.78 (4H, m), 1,94-of 2.09 (3H, s), 3,80 (2H, d, J=7,3 Hz), of 6.52 (1H, DD, J=3.3, which is 1.8 Hz), 7,52-rate of 7.54 (1H, m), 7,92 (1H, d, J=2.0 Hz), of 8.25 (2H, d, J=2.0 Hz), 8,55 (1H, d, J=2.2 Hz), to 11.61 (1H, s), 11,74 (1H, s).

(Example 104)

1-{[TRANS-3-Methoxycyclohexyl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

(TRANS-3-methoxycyclohexyl)methanol

(CIS-3-methoxycyclohexyl)methanol

Specified in the title compound, TRANS-isomer (0,41 g) and CIS-isomer (0.39 g)was obtained in a way similar to step 2 of example 33, using 3-methoxycyclohexanone acid (2.0 g).

the TRANS-isomer

1H-NMR (CDCl3) δ: 1,02-of 1.05 (1H, m), 1,14-to 1.21 (1H, m), 1,25-of 1.27 (1H, m), 1,33-of 1.36 (1H, m), 1,49-of 1.56 (1H, m), 1,71 is 1.75 (1H, m), 1,84-of 1.94 (3H, m), and 3.31 (3H, s), 3,45-3,47 (2H, m), 3,53-of 3.54 (1H, m).

CIS-isomer

1H-NMR (CDCl3) δ: 0,85-0,89 (2H, m), 1,09 is 1.16 (1H, m), 1,23-of 1.30 (1H, m), 1,53-of 1.57 (1H, m), 1.70 to about 1.75 (1H, m), 1,82-of 1.85 (1H, m), 2.05 is-of 2.08 (1H, m), 2,13-to 2.15 (1H, m), 3,13-3,18 (1H, m)to 3.36 (3H, s), 3,50-3,51 (2H, m).

Stage 2

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[TRANS-4-methoxycyclohexyl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (281 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (280 mg), (TRANS-3-methoxycyclohexyl)methanol obtained in the above stage 1 (164 mg), and bis(2-methoxyethyl)azodicarboxylate instead of diisopropylcarbodiimide (267 mg).

MS (APCI) m/z: 420 [M+H]+.

1H-NMR (DMSO-d6) δ: equal to 1.03-1.05 (1H, m), 1,16-1,22 (1H, m), of 1.28 and 1.33 (1H, m), 1,40 was 1.43 (2H, m), of 1.52-1.55V (1H, m), 1,60 to 1.76 (6H, m), 2.05 is-2,10 (1H, m), 2.21 are 2,22 (2H, m), 2,32 of-2.32 (2H, m), 3,17 (3H, s), 3.46 in-of 3.48 (1H, m), 3,68 (2H, d, J=7,6 Hz), 5,91-to 5.93 (1H, m), to $ 7.91 (1H, d, J=2.1 Hz), of 8.06 (1H, d, J=2.1 Hz).

Stage 3

3-Cyclohex-1-EN-1-yl-1-{[TRANS-3-methoxycyclohexyl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (142 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (168 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 458 [M+H]+.

1H-NMR (CDCl3) δ: 1,09-1,98 (12H, m), 2,25-is 2.37 (3H, m), 2,47 of $ 2.53 (2H, m)of 3.25 (4H, s), 3,54-3,59 (1H, m), with 3.79 (2H, d, J=7,3 Hz), 6,06-6,09 (1H, m), 6,60 (1H, DD, J=3,7, 1.8 Hz), 7,37 (1H, d, J=1,8 Hz), 7,39-7,42 (1H, m,), of 8.09 (1H, d, J=1,8 Hz), of 8.28 (1H, d, J=1,8 Hz)and 8.50 (1H, s), a 9.35 (1H, s).

Stage 4

1-{[TRANS-3-methoxycyclohexyl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (86 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (141 mg).

MS (APCI) m/z: 378 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,02-of 1.42 (5H, m), 1,54-of 1.57 (1H, m), 1,69-1,72 (2H, m), 2,12-to 2.15 (1H, m)to 3.09 (3H, s), 3,44-3,47 (1H, user. m)to 3.73 (2H, d, J=16,3 Hz), 6,50 (1H, DD, J=3.2, and 1.8 Hz), 7,51 (1H, t, J=3.0 Hz), to 7.84 (1H,d, J=1,8 Hz), by 8.22 (2H, d, J=1,8 Hz), charged 8.52 (1H, d, J=2.3 Hz), 11,57 (1H, user. C)11,72 (1H, user. C).

(Example 105)

1-{[CIS-3-methoxycyclohexyl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

and its enantiomer

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[CIS-4-methoxycyclohexyl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (215 mg) was obtained in a way similar to step 2 of example 104, using the compound obtained in stage 2 of example 35 (280 mg), and (CIS-3-methoxycyclohexyl)methanol obtained in stage 1 of example 104 (164 mg).

MS (APCI) m/z: 420 [M+H]+.

1H-NMR (DMSO-d6) δ: 0,83-a 1.01 (2H, m), 1,13-to 1.21 (1H, m)and 1.51-of 1.54 (1H, m), 1,67-of 1.78 (6H, m), 1,94-of 1.97 (2H, m), 2.21 are of 2.21 (2H, m), 2,32 is 2.33 (2H, m), 3,06-3,11 (1H, m), 3,21 (3H, s), 3,66-of 3.77 (2H, m), 5,91-to 5.93 (1H, m), a 7.92 (1H, d, J=2.0 Hz), 8,07 (1H, d, J=2.0 Hz).

Stage 2

3-Cyclohex-1-EN-1-yl-1-{[CIS-3-methoxycyclohexyl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (124 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (168 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 458 [M+H]+.

1H-NMR (CDCl3) δ: 0,98-of 1.94 (10H, m), 1,97 and 2.13 (3H, m), 2,32 to 2.35 (2H, m), 2,49-2,52 (2H, m), 3,11 -, and 3.16 (1H, m)to 3.33 (3H, s), 3,81 (2H, DDD, J=2,9, to 7.2, 3.6 Hz), 6,07-6,09 (1H, m), 6,60 (1H, DD, J=3,7, 1.8 Hz), was 7.36 (1H, d, J=1,8 Hz), the 7.43 (1H, t, J=2.7 Hz), of 8.09 (1H, d, J=2.3 Hz), 8,29 (1H, d, J=1,8 Hz), 8,51 (1H, d, J=2.3 Hz), 9,80 (1H, user. C).

Stage 3

1-{[CIS-3-Methoxycyclohexyl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (86 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (123 mg).

MS (APCI) m/z: 378 [M+H]+.

1H-NMR (DMSO-d6) δ: 0,86-a 1.01 (3H, m), 1,11-of 1.15 (1H, m), of 1.52-1.55V (1H, m), 1,67-1,71 (1H, m), 1,83 is 1.96 (3H, m), 3,02-of 3.07 (1H, m), 3,17 (3H, s), 3.72 points-of 3.77 (2H, m), 6,50 (1H, DD, J=3,4, and 1.6 Hz), 7,51 (1H, t, J=3.0 Hz), 7,86 (1H, d, J=1,8 Hz), 8,23 (2H, d, J=1,8 Hz), 8,53 (1H, d, J=2.3 Hz), 11,57 (1H, user. C)11,72 (1H, user. C).

(Example 106)

1-[(4-Exoterica-2H-Piran-3-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

Ethyl 4-exoterica-2H-Piran-3-carboxylate

In a solution of tetrahydro-4H-Piran-4-it (260 mg) in tetrahydrofuran (13 ml) at -78°C was added dropwise diisopropylamide lithium (1,14 mol/l solution in a mixture of n-hexane/tetrahydrofuran, 2.5 ml) and the mixture was stirred for one hour while heating to 0°C. the Reaction solution was again cooled to -78°C, was added hexamethylphosphoric triamide (452 μl) and then added ethylcyanoacrylate (280 μl) at the same temperature. The mixture was stirred for about the nogo hours when heated to 0°C. The reaction solution was separated by adding distilled water and ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (210 mg).

1H-NMR (CDCl3) δ: of 1.30 (3H, t, J=6.9 Hz), a 2.36-to 2.42 (2H, m), 3,82-3,88 (2H, m), 4,23 (3H, q, J=7,3 Hz), the 4.29-4.26 deaths (2H, m), up 11,86 (1H, s).

Stage 2

Ethyl 1,4,8-dioxaspiro[4,5]decane-6-carboxylate

Into a solution of the compound obtained in the above stage 1 (860 mg)in dichloromethane (50 ml) at room temperature was added bis(trimethylsiloxy)ethane (3,68 ml). The reaction solution was cooled to -15°C and added trimethylsilyltrifluoromethane (92 μl). The mixture was stirred for 2 hours while warming to 0°C and then stirred at room temperature for 3.5 hours. Under ice cooling was added pyridine (0.2 ml) and then the mixture was separated by adding dichloromethane and saturated aqueous sodium bicarbonate solution. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column with what likehell (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (956 mg).

1H-NMR (CDCl3) δ: of 1.28 (3H, t, J=7,3 Hz)of 1.65 and 1.75 (1H, m), 2,00-2,09 (1H, m), 2,75-2,82 (1H, m), 3.75 to of 3.85 (2H, m), 3,90-a 4.03 (6H, m), 4,18 (2H, q, J=6.9 Hz).

Stage 3

1,4,8-Dioxaspiro[4,5]Dec-6-ylmethanol

Specified in the title compound (152 mg) was obtained in a way similar to step 2 of example 33 using the compound obtained in the above stage 2 (211 mg), and alumoweld lithium (60 mg).

1H-NMR (CDCl3) δ: 1,17-of 1.27 (1H, m), 1,60-1,70 (1H, m), 1,81-1,90 (1H, m), 1,98 e 2.06 (1H, m), 2,45-2,52 (1H, m), 3,76-of 3.64 (4H, m), 3,92 is 3.76 (4H, m).

Stage 4

6-Bromo-3-cyclohex-1-EN-1-yl-1-(1,4,8-dioxaspiro[4,5]Dec-6-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (120 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in the above stage 3 (151 mg)and the compound obtained in stage 2 of example 35 (243 mg).

MS (ESI) m/z: 450 (M+H)+.

1H-NMR (CDCl3) δ: 1,61-of 1.78 (3H, m), 1,82-of 1.92 (3H, m), 2,24-of 2.34 (3H, m), 2,37 is 2.44 (2H, m), 3,49 (1H, d, J=5.5 Hz), 3,55-3,63 (1H, m), 3,74-to 3.89 (4H, m), 3.96 points-of 4.11 (4H, m), 6,03-5,96 (1H, m), 7,40 (1H, d, J=1,8 Hz), 8,09 (1H, d, J=1,8 Hz).

Stage 5

3-Cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(1,4,8-dioxaspiro[4,5]Dec-6-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (94 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (115 what g), and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (76 mg).

MS (ESI) m/z: 488 (M+H)+.

1H-NMR (CDCl3) δ: 1,62-1,71 (1H, m), 1,73-of 1.81 (2H, m), 1.85 to 1,95 (3H, m), 2,30-to 2.40 (3H, m), 2,45 of $ 2.53 (2H, m), 3,62 at 3.69 (1H, m), of 3.77-a-3.84 (3H, m), 3,92-to 4.15 (6H, m), 6,03-6,09 (1H, m), 6,58-6,62 (1H, m), of 7.36-7,40 (1H, m,), to 7.50 (1H, d, J=1,8 Hz), 8,08 (1H, d, J=2.3 Hz), of 8.28 (1H, d, J=1,8 Hz)and 8.50 (1H, d, J=2.3 Hz), the rate of 8.75 (1H, user. C).

Stage 6

1-[(4-Exoterica-2H-Piran-3-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (11 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 5 (90 mg).

MS (ESI) m/z: 346 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H17N5O3364,14096; found: 364,14502.

1H-NMR (DMSO-d6) δ: 2,34-2,47 (2H, m), 3,20-3,51 (4H, m), 4,59 (2H, s), 6,47-of 6.52 (1H, m), 7,40-7,44 (1H, m), 7,49-7,53 (1H, m), 7,74 (1H, d, J=2.3 Hz), 8,19 (1H, d, J=1,8 Hz), 8,24 (1H, d, J=1,8 Hz), 8,49 (1H, d, J=2,3 Hz), 11,65 (1H, user. C)11,71 (1H, user. C).

(Example 107)

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydrofuran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-3-cyclohex-1-EN-1-yl-1-(tetrahydrofuran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (85 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage Primera 35 (100 mg), and tetrahydrofuran-3-ylmethanol (42 μl).

MS (APCI) m/z: 378 [M+H]+.

1H-NMR (CDCl3) δ: 1,71-to 1.79 (5H, m), 1,86-of 1.88 (2H, m), 2,01-of 2.09 (1H, m), 2,30 of-2.32 (2H, m), 2,39 is 2.44 (2H, m), 2,78-to 2.85 (1H, m)to 3.64 (1H, DD, J=8,9, and 4.8 Hz), of 3.77-of 3.80 (3H, m), 3,90 (1H, DD, J=14.2 per cent and 7.6 Hz), 3,99 (1H, TD, J=8,2, 5.8 Hz), 6,00-6,03 (1H, m), 7,34 (1H, d, J=2.0 Hz), 8,10 (1H, d, J=2.0 Hz).

Stage 2

6-Bromo-1-(tetrahydrofuran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (55 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (85 mg).

MS (APCI) m/z: 298 [M+H]+.

Stage 3

6-(1H-Pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydrofuran-3-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (39 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (55 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (50 mg).

MS (APCI) m/z: 336 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,64-to 1.67 (1H, m), 1,89-of 1.94 (1H, m), 2,48-of 2.50 (4H, m), was 2.76-2,82 (1H, m), 3,51 (1H, DD, J=8,4, 5,5 Hz), 3,61-to 3.67 (2H, m), 3,80 (1H, TD, J=8.0 a, 5,5 Hz), a 3.87 (2H, d, J=7,6 Hz), 6,50 (1H, DD, J=3.1 and 1.8 Hz), 7,51 (1H, t, J=3.1 Hz), 7,92 (1H, d, J=2.1 Hz), 8,24 (2H, d, J=1,8 Hz), charged 8.52 (1H, d, J=2.1 Hz), to 11.61 (1H, s), 11,71 (1H, user. C).

(Example 108)

1-(Morpholine-3-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

tert-Butyl 3-[(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)methyl]morpholine-4-carboxylate

Specified in the title compound (469 mg) was obtained by the method used in stage 3 of example 35 using the compound obtained in stage 2 of example 35 (471 mg)and tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate obtained by the method described in WO 2006/99352 (521 mg).

MS (APCI) m/z: 493 [M+H]+.

Stage 2

tert-Butyl 3-{[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]methyl}morpholine-4-carboxylate

Specified in the title compound (177 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (197 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 531 [M+H]+.

Stage 3

1-(Morpholine-3-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (64 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (177 mg).

MS (APCI) m/z: 351 [M+H]+.

1H-NMR (DMSO-d6) δ: 2,62-to 2.65 (1H, m), was 2.76 (1H, d, J=10.0 Hz), 3,06-is 3.08 (1H, m), 3,20 (1H, t, J=9.8 Hz), to 3.58 (1H, d, J=11,0 Hz), 3,70-with 3.79 (4H, m), 6,50 (1H, t, J=1.6 Hz), 7,51 (1H, d, J=2.3 Hz), 7,87 (1H, d, J=1,8 Hz), 8,23 (2H, d, J=1,8 Hz), charged 8.52 (1H, d, J=1 Hz), 11,72 (1H, user. C).

(Example 109)

1-{[(3S)-4-Methyl-5-exmortis-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

N-[(1R)-2-(Benzyloxy)-1-(hydroxymethyl)ethyl]-2-chloracetamide

(2R)-2-Amino-3-(benzyloxy)propan-1-ol (2,18 g) was dissolved in acetonitrile (38 ml) and methanol (7 ml) was added triethylamine (2.0 ml). The atmosphere was replaced with nitrogen and then the mixture was cooled to -10°C. was added dropwise a solution of chloroacetaldehyde (1,05 ml) in acetonitrile (9 ml) and the mixture was stirred for 20 hours with gradual warming to room temperature. Drove the solvent of the reaction mixture and the residue was directly purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (of 2.26 g).

MS (APCI) m/z: 258 [M+H]+.

1H-NMR (CDCl3) δ: of 3.64 (1H, DD, J=9,5, 4,1 Hz), 3,69-to 3.73 (2H, m), a 3.87 (1H, DD, J=11,3, 4.0 Hz), of 4.05 (2H, d, J=2,9 Hz), 4,11-4,13 (1H, m), 4,55 (2H, s), 7,22 (1H, user. C), 7,32-7,37 (5H, m).

Stage 2

(5S)-5-[(Benzyloxy)methyl]morpholine-3-one

Tert-piperonyl potassium (982 mg) was dissolved in 2-methylbutane-2-OLE (7 ml). In nitrogen atmosphere for one hour was added dropwise a solution of the compound obtained in the above stage 1 (2,254 g), 2-methylbutane-2-OLE (15 ml). After complete addition, the mixture was additionally stirred for one hour a mortgage solvent of the reaction mixture is kept off. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-ethanol) to obtain specified in the connection header (807 mg).

MS (APCI) m/z: 222 [M+H]+.

1H-NMR (CDCl3) δ: 3,43 (1H, DD, J=9,0, 8.1 Hz), 3,55 (1H, DD, J=9,0, 5,5 Hz)to 3.64 (1H, DD, J=11,7, 5,5 Hz), 3.72 points is 3.76 (1H, m), 3,86 (1H, DD, J=11,7, 3.8 Hz), 4,15 (2H, d, J=4.4 Hz), of 4.54 (2H, DD, J=13,4, 11.7 Hz), 6,60 (1H, user. C), 7,29-7,39 (5H, m).

Stage 3

(5S)-5-[(Benzyloxy)methyl]-4-methylmorpholin-3-one

The compound obtained in the above stage 2 (449 mg)was dissolved in tetrahydrofuran (6 ml) and the solution was cooled with ice in a nitrogen atmosphere. Was added 55% sodium hydride (133 mg) and the mixture was stirred under ice cooling for 30 minutes. After adding tetrahydrofuran (18 ml) was added methyliodide (695 μl) and the mixture was stirred for 25 hours with gradual warming to room temperature. The reaction solution was extracted with a single addition of toluene and the aqueous layer was extracted with ethyl acetate three times. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate) to obtain the specified title compound (454 mg).

MS (APCI) m/z: 236 [M+H]+.

1H-NMR (CDCl3) δ: to 3.02 (3H, s), 3,36-to 3.41 (1H, m), the 3.65 (1H, DD, J=9,3, 4.6 Hz), 370 (1H, t, J=8.7 Hz), 3,76 (1H, DD, J=11.8 in, 3.1 Hz), 4,06 (1H, DD, J=12,0, 1.5 Hz), is 4.15 (2H, q, J=16.4 Hz), 4,56 (2H, t, J=12,5 Hz), 7,29-7,39 (5H, m).

Stage 4

(5S)-5-(Hydroxymethyl)-4-methylmorpholin-3-one

The compound obtained in the above stage 3 (454 mg), was dissolved in ethanol and was added 20% palladium hydroxide. The mixture was subjected to interact in an atmosphere of hydrogen at room temperature for 14 hours. The solvent of the reaction mixture was filtered through celite, washed with ethanol and then drove away. The residue was dissolved in a small amount of acetonitrile and the solution was filtered through a cotton filter. The filtrate was concentrated to obtain specified in the title compound (276 mg) as a colourless oil.

MS (APCI) m/z: 146 [M+H]+.

1H-NMR (CDCl3) δ: a 3.06 (3H, s), 3,28-of 3.32 (1H, m), 3,81-to 3.92 (3H, m).

Stage 5

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[(3S)-4-methyl-5-exmortis-3-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (318 mg) was obtained as colorless needle-like crystals in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (235 mg)and the compound obtained in the above stage 4 (174 mg).

MS (APCI) m/z: 421 [M+H]+.

1H-NMR (CDCl3) δ: 1,71-to 1.79 (2H, m), 1,83 is 1.91 (2H, m), 2,28 is 2.46 (4H, m), 3,14 (3H, s), 3,62-3,68 (1H, m), 3,71-3,81 (2H, m)4,00 (1H, DD, J=14,0, 9.9 Hz), 4,18 (1H, DDD, J=14.2 per cent, of 3.9, 1.2 Hz), 4,19 (1H,d, J=16.6 Hz), 4,35 (1H, d, J=16.6 Hz), 6,00-6,03 (1H, m), the 7.43 (1H, d, J=2.0 Hz), 8,13 (1H, d, J=2.0 Hz).

Stage 6

3-Cyclohex-1-EN-1-yl-1-{[(3S)-4-methyl-5-exmortis-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (133 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 5 (169 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 459 [M+H]+.

Stage 7

1-{[(3S)-4-Methyl-5-exmortis-3-yl]methyl}-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above stage 6 (133 mg), was dissolved in a solvent consisting of ethanol (1 ml), water (0.5 ml) and concentrated sulfuric acid (0.5 ml)and the mixture was stirred at 80°C for three days. The reaction solution was neutralized with sodium carbonate and then concentrated to dryness. The residue was dissolved in 1,4-dioxane (10 ml) and 4 G. hydrochloric acid (10 ml) and the solution was stirred at room temperature for two days. After extraction with a mixture of dichloromethane/methanol (9/1) inorganic salt was removed with PorapakTMRxnCX, then suirable 5% aqueous mixture of ammonia/ethanol. The eluate was concentrated and then dissolved in ethanol (3 ml) and water (1 ml). Added chloride 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-metilo Polina (160 mg) and the mixture was stirred at room temperature for 14 hours. The solvent was concentrated and then added water, and then sufficiently stirred. The insoluble substance was collected by filtration, washed with water and ethyl acetate and then dried by suction to obtain specified in the title compound (30 mg) in the form of crystalline substances cream color.

MS (APCI) m/z: 379 [M+H]+.

1H-NMR (DMSO-d6) δ: 2.91 in (3H, s), 3,59-4,22 (7H, m), of 6.49-of 6.52 (1H, m), 7,50-7,53 (1H, m), 7,72-7,76 (1H, m), 8,20 is 8.22 (1H, m), 8,23-of 8.25 (1H, m), 8,49-charged 8.52 (1H, m), 11,72 (2H, user. C).

(Example 110)

1-[(5-Exmortis-2-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-(Hydroxymethyl)morpholine-3-one

Tert-piperonyl potassium (1.08 g) was dissolved in 2-methylbutane-2-OLE (7.7 ml). A solution of 2-chloro-N-(2,3-dihydroxypropyl)ndimethylacetamide, obtained by the method described in WO 2007/6715 (1,61 g), 2-methylbutane-2-OLE (16.4 ml) was added dropwise in a nitrogen atmosphere for one hour. After complete addition, the mixture was further stirred for one hour and then the solvent of the reaction mixture is kept off. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-ethanol) to obtain the specified title compound (488 mg).

MS (APCI) m/z: 132 [M+H]+.

1H-NMR (DMSO-d6) δ: of 3.07 (1H, t, J=11.2 Hz), 3,13-3,20 (1H, m), 3,38-3,51 (2H, m), 3,62-3,68 (1H, m)4,00 (2H, d, J=5.6 Hz).

Stage 2

p> 6-Bromo-3-cyclohex-1-EN-1-yl-1-[(5-exmortis-2-yl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (285 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (235 mg)and the compound obtained in the above stage 1 (157 mg).

MS (APCI) m/z: 407 [M+H]+.

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(5-exmortis-2-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (117 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (163 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (107 mg).

MS (APCI) m/z: 445 [M+H]+.

Stage 4

1-[(5-Exmortis-2-yl)methyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (61 mg) was obtained in a way similar to stage 7 of example 109, using the compound obtained in the above stage 3 (117 mg).

MS (APCI) m/z: 365 [M+H]+.

1H-NMR (DMSO-d6) δ: 3,93-to 4.15 (7H, m), of 6.49 (1H, DD, J=3,7, 1.8 Hz), 7,51 (1H, t, J=2.3 Hz), to 7.84 (1H, d, J=2.3 Hz), 7,98 (1H, d, J=3,7 Hz), by 8.22 (1H, d, J=2.3 Hz), 8,24 (1H, d, J=1,8 Hz), charged 8.52 (1H, d, J=2.3 Hz), 11,64 (1H, user. C)11,71 (1H, user. C).

(Example 111)

2,6-Anhydrous-1,3,4-trideoxy-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-Erythro-hexitol

and its enantiomer

Stage 1

2,6-Anhydrous-5-O-benzoyl-1-O-[tert-butyl(diphenyl)silyl]-3,4-dideoxy-DL-Erythro-hexitol

2,6-Anhydrous-1-O-[tert-butyl(diphenyl)silyl]-3,4-dideoxy-DL-Erythro-hexitol obtained by the method described in Bioorg. Med. Chem. 2006, 14, 3953 (542 mg)was dissolved in methylene chloride (15 ml). Pyridine (236 μl) and benzoyl chloride (255 ml) was sequentially added under ice cooling and the mixture was stirred at room temperature overnight. To the reaction solution was added water, then was extracted with ethyl acetate. Next, the organic layer is successively washed with 10% aqueous citric acid solution, saturated aqueous sodium bicarbonate and saturated saline solution. The obtained organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (285 mg) as a solid brown color.

1H-NMR (CDCl3) δ with 1.07 (9H, s), 1,52 is 1.58 (1H, m), 1,60-1,70 (1H, m), 1,88-of 1.93 (1H, m), 2,28 is 2.33 (1H, m)to 3.35 (1H, t, J=10.4 Hz), 3.43 points-to 3.49 (1H, m)and 3.59 (1H, DD, J=a 10.5, 5.6 Hz), 3,76 (1H, DD, J=10,3, a 5.4 Hz), 4,13-4,17 (1H, m), 4,98-5,04 (1H, m), 7,37 was 7.45 (8H, m), 7,54-7,58 (1H, m), 7,66-of 7.69 (4H, m), 8,01-8,03 (2H, m).

Stage 2

2,6-Anhydrous-5-O-benzoyl-3,4-dideoxy-DL-Erythro-Exito the

Specified in the title compound (180 mg) was obtained in the form of a solid brown color way, similar to the one used in stage 4 of example 62, using the compound obtained in the above stage 1 (400 mg).

1H-NMR (CDCl3) δ: 1.56 to to 1.61 (1H, m), of 1.66 to 1.76 (2H, m)to 1.98 (1H, user. C)of 2.30 to 2.35 (1H, m), 3,40 (1H, t, J=10,6 Hz), 3,47-to 3.52 (1H, m), 3,55-3,59 (1H, m), 3,63-to 3.67 (1H, m), 4,20-to 4.23 (1H, m), 4,99-of 5.06 (1H, m), 7,44 (2H, t, J=7,7 Hz), EUR 7.57 (1H, t, J=7.5 Hz), 8,02 (2H, d, J=6,9 Hz).

Stage 3

2,6-Anhydrous-5-O-benzoyl-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-DL-Erythro-hexitol

Specified in the title compound (315 mg) was obtained as a colourless solid in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (200 mg)and the compound obtained in the above stage 2 (176 mg).

MS (ESI) m/z: 512 (M+H)+.

1H-NMR (CDCl3) δ: 1,59-of 1.78 (4H, m), 1,84-1,89 (2H, m), 1,91 is 1.96 (1H, m), 2,29-of 2.34 (3H, m), 2,42 at 2.45 (2H, m), 3,29 (1H, m), 3,68-3,74 (1H, m), with 3.79 (1H, DD, J=14,4, 7,3 Hz), was 4.02 (1H, DD, J=14,4, 2.7 Hz), 4,14-4,18 (1H, m), 4,96-5,04 (1H, m), 6,01-6,03 (1H, m), 7,41 was 7.45 (2H, m), 7,51 (1H, d, J=2.0 Hz), 7,54-7,58 (1H, m), 7,99 shed 8.01 (2H, m), of 8.09 (1H, d, J=2.0 Hz).

Stage 4

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-DL-Erythro-hexitol

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (85 mg) was combined with Saedinenie, obtained in the above stage 3 (150 mg)in a manner similar to the one used in stage 3 of example 1. Then the obtained residue was dissolved in methanol (5 ml), was added potassium carbonate (81 mg) under ice cooling and the mixture was stirred overnight while gradually warming to room temperature. The solvent of the reaction mixture is kept under reduced pressure, diluted with ethyl acetate and washed with saturated saline solution. The obtained organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (92 mg) as a solid light yellow color.

MS (ESI) m/z: 446 (M+H)+.

1H-NMR (CDCl3) δ: 1,43-is 1.51 (3H, m), a 1.75-to 1.79 (2H, m), 1,88 is 1.91 (3H, m), 2,15-2,19 (1H, m), 2,32-of 2.36 (2H, m), 2,49-2,52 (2H, m), is 3.08 (1H, t, J=10,6 Hz), 3,65-3,71 (2H, m), 3,88 (1H, DD, J=14,6, 7,2 Hz), 3.96 points-of 4.00 (1H, m), 4,06 (1H, DD, J=14,6, and 3.2 Hz), between 6.08 (1H, s), 6,58-6,60 (1H, m), 7,38 (1H, t, J=2,9 Hz), EUR 7.57 (1H, d, J=1.7 Hz), 8,07 (1H, d, J=1.7 Hz), of 8.28 (1H, d, J=1.7 Hz), 8,49 (1H, d, J=1.7 Hz), 8,88 (1H, user. C).

Stage 5

2,6-Anhydrous-1,3,4-trideoxy-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-Erythro-hexitol

Specified in the title compound (7 mg) was obtained in the form of a matte-white solid in a manner analogous inputs the WMD at the stage 6 of example 35, using the compound obtained in the above stage 4 (90 mg).

HRMS (ESI) [M+H]+calculated: C19H20N5O3366,15661; found: 366,15678.

MS (ESI) m/z: 366 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,24-of 1.36 (2H, m), 1,69-of 1.73 (1H, m), 1,92-of 1.97 (1H, m), 2,89 (1H, t, J=10.4 Hz), 3,37-of 3.43 (1H, m), to 3.58-of 3.64 (1H, m), 3.72 points is 3.76 (1H, m), 3,82-of 3.95 (2H, m), was 4.76 (1H, d, J=4.9 Hz), of 6.52 (1H, DD, J=3.3V, 1,8 Hz), 7,53 (1H, t, J=2,8 Hz), 7,80 (1H, d, J=2.0 Hz), by 8.22-8,23 (2H, m), charged 8.52 (1H, d, J=2.0 Hz), 11,59 (1H, user. C)11,74 (1H, user. C).

(Example 112)

2,6-Anhydrous-1,3,4-trideoxy-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

and its enantiomer

Stage 1

2,6-Anhydrous-5-O-benzoyl-1-O-[tert-butyl(diphenyl)silyl]-3,4-dideoxy-DL-threo-hexitol

2,6-Anhydrous-1-O-[tert-butyl(diphenyl)silyl]-3,4-dideoxy-DL-Erythro-hexitol obtained by the method described in Bioorg. Med. Chem. 2006, 14, 3953 (4.35 g)was dissolved in tetrahydrofuran (80 ml) was added benzoic acid (1,72 g) and triphenylphosphine (3,69 g). Was added dropwise while cooling with ice diisopropylsalicylic (2,87 ml) and the mixture was stirred for one hour while gradually warming to room temperature. The reaction solution was diluted with ethyl acetate and the organic layer was sequentially washed with water, 10% aqueous citric acid solution, saturated aqueous sodium bicarbonate and saturated saline RA is tworoom. The obtained organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain specified in the connection header (2,94 g) as a colourless oil.

1H-NMR (CDCl3) δ with 1.07 (9H, s), 1,62-of 1.66 (1H, m), 1,82-to 1.87 (2H, m), 2,13-to 2.18 (1H, m), 3,48-of 3.54 (1H, m), 3,64 at 3.69 (2H, m), of 3.78 (1H, DD, J=10,5, 5,1 Hz), 4,11-4,16 (1H, m), is 5.06 (1H, s), 7,35-7,44 (8H, m), 7,53-7,58 (1H, m), to 7.67-7,71 (4H, m), 8.07-a of 8.09 (2H, m).

Stage 2

2,6-Anhydrous-5-O-benzoyl-3,4-dideoxy-DL-threo-hexitol

Specified in the header of the connection (of 0.43 g) was obtained as colorless oil by the method similar to that applied in stage 4 of example 62, using the compound obtained in the above stage 1 (1 g).

MS (ESI) m/z: 237 (M+H)+.

1H-NMR (CDCl3) δ: 1,47-is 1.51 (1H, m), 1,79-of 1.93 (2H, m), is 2.05 (1H, DD, J=7,5, 4.6 Hz), 2,16-of 2.20 (1H, m), 3,55 at 3.69 (3H, m), 3,74 (1H, DD, J=12,9, and 1.4 Hz), 4,20 (1H, m), 5,09 (1H, s), 7,44-7,47 (2H, m), 7,56-to 7.59 (1H, m), 8,08-8,10 (2H, m).

Stage 3

2,6-Anhydrous-5-O-benzoyl-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-DL-threo-hexitol

Specified in the title compound (810 mg) was obtained as a colourless solid in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (480 mg)and the compound obtained is described in the above stage 2 (424 mg).

MS (ESI) m/z: 512 (M+H)+.

1H-NMR (CDCl3) δ: 1,64 by 1.68 (1H, m), 1,72-of 1.78 (3H, m), 1,84-1,89 (3H, m), 2,14-2,19 (1H, m), 2,29-2,31 (2H, m), 2.40 a is 2.43 (2H, m), the 3.65 (1H, DD, J=12,9, and 1.4 Hz), 3,78-3,82 (1H, m), 3,93-4,01 (2H, m), 4,13-4,17 (1H, m), 5,04 (1H, s), 6,00-6,01 (1H, m), 7,42 (2H, t, J=8.0 Hz), 7,55-7,58 (2H, m), 7,92 (2H, DD, J=8,0, 1.2 Hz), 8,08 (1H, d, J=1.7 Hz).

Stage 4

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-DL-threo-hexitol

Specified in the title compound (174 mg) was obtained as a pale yellow oil in a way similar to stage 4 of example 111 using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (171 mg) and the compound obtained in the above stage 3 (300 mg).

MS (ESI) m/z: 446 (M+H)+.

1H-NMR (CDCl3) δ: 1,62-of 1.66 (2H, m), 1,73-of 1.81 (3H, m), 1,88-of 1.93 (2H, m), 1,95 of 1.99 (1H, m), 2,14-to 2.18 (1H, m), 2,33-of 2.36 (2H, m), 2,49-2,52 (2H, m), of 3.56 (1H, DD, J=13,2, 1.7 Hz), 3,74-with 3.79 (2H, m), 3,89-of 3.95 (2H, m)4,06 (1H, DD, J=14,6, and 3.2 Hz), 6,07-6,09 (1H, m), 6,59 (1H, DD, J=3,4, and 2.3 Hz), 7,39-7,40 (1H, m), 7,60 (1H, d, J=1.7 Hz), 8,07 (1H, d, J=2.3 Hz), of 8.28 (1H, d, J=1.7 Hz), 8,49 (1H, d, J=2.3 Hz), 9,20 (1H, user. C).

Stage 5

2,6-Anhydrous-1,3,4-trideoxy-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

Specified in the title compound (10 mg) was obtained as a pale yellow solid in a way similar to the stage 6 of example 35 using the compound obtained in the above a hundred of the AI 4 (170 mg).

MS (ESI) m/z: 366 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,61-of 1.73 (2H, m), 3,36-3,39 (1H, m), 3,53-3,70 (3H, m), 3,82-3,86 (1H, m), 3,94-to 3.99 (1H, m), of 4.57 (1H, d, J=4.0 Hz), 6,51 (1H, DD, J=3,4, 1.7 Hz), 7,53 (1H, t, J=2,9 Hz), 7,82 (1H, d, J=1.7 Hz), by 8.22 (2H, t, J=2.3 Hz), charged 8.52 (1H, d, J=2.3 Hz), 11,59 (1H, s), 11,74 (1H, s).

(Example 113)

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

and its enantiomer

Stage 1

2,6-Anhydrous-1-O-[tert-butyl(diphenyl)silyl]-3,4-dideoxy-DL-threo-hexitol

The compound obtained in stage 1 of example 112 (1 g), was dissolved in methanol (20 ml). Was added potassium carbonate (0,58 g) under ice cooling and the mixture was stirred for day and night during the gradual heating to room temperature. Under reduced pressure drove the solvent of the reaction mixture then was diluted with ethyl acetate. The organic layer was washed with saturated brine and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (0,69 g) as a colourless oil.

MS (ESI) m/z: 393 (M+Na)+.

1H-NMR (CDCl3) δ: of 1.06 (9H, s), 1,65-1,70 (2H, m), 1,91-of 1.95 (1H, m), 2,16-to 2.18 (1H, m), 3.43 points-of 3.48 (1H, m), 3,55-of 3.60 (2H, m), 3,71-,76 (2H, m), 3,88 (1H, m), of 7.36-7,44 (6H, m), 7,66-to 7.68 (4H, m).

Stage 2

2,6-Anhydrous-1-O-[tert-butyl(diphenyl)silyl]-3,4-dideoxy-5-O-methyl-DL-threo-hexitol

Specified in the header connection (0,69 g) was obtained as colorless oil by the method similar to those used in stage 1 of example 63, using the compound obtained in the above stage 1 (0.68 g).

MS (ESI) m/z: 407 (M+Na)+.

1H-NMR (CDCl3) δ: of 1.05 (9H, s), 1,59-of 1.64 (3H, m), 2,04-of 2.08 (1H, m), 3,23 (1H, user. C)to 3.35 (3H, s), 3,44-3,50 (2H, m), of 3.54 (1H, DD, J=10,0, and 6.6 Hz), 3,76 (1H, DD, J=10,0, 5,4 Hz), Android 4.04 (1H, m), 7,35-7,42 (6H, m), 7,66 (4H, DD, J=8,0, 1.2 Hz).

Stage 3

2,6-Anhydrous-5-O-benzoyl-3,4-dideoxy-DL-threo-hexitol

Specified in the title compound (220 mg) was obtained as colorless oil by the method similar to that applied in stage 4 of example 62, using the compound obtained in the above stage 2 (600 mg).

1H-NMR (CDCl3) δ: 1,58 is 1.70 (2H, m), 2.06 to 2,11 (1H, m), 3,26 of 3.28 (1H, m), 3,37 (3H, s), 3.46 in-3,49 (1H, m), 3,49-of 3.53 (1H, m), 3,56-3,59 (2H, m), 4,11 (1H, m).

Stage 4

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-5-O-methyl-DL-threo-hexitol

Specified in the title compound (440 mg) was obtained as a colourless solid in a way similar to stage 3 of example 35 using the compound obtained in stage 2 of example 35 (330 mg)and the compound obtained in the above stage 3 (180 mg).

MS (ESI) /z: 424 (M+H) +.

1H-NMR (CDCl3) δ: 1,52-of 1.55 (1H, m), 1,57 was 1.69 (1H, m), 1,71-to 1.77 (3H, m), 1,83-1,89 (2H, m), 2,12 (1H, m), 2,28 of-2.32 (2H, m), 2.40 a is 2.44 (2H, m), 3,24 (1H, s), 3,39 (3H, s)to 3.41 (1H, DD, J=12,6, 1,6 Hz), 3,65-of 3.77 (2H, m)that is 4.00 (1H, DD, J=14,0, 2,5 Hz), a 4.03-4,08 (1H, m), 5,99-6,01 (1H, m), 7,60 (1H, d, J=1,8 Hz), of 8.06 (1H, d, J=1,8 Hz).

Stage 5

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-DL-threo-hexitol

Specified in the title compound (210 mg) was obtained as a pale yellow oil in a way similar to step 2 of example 4, using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (138 mg) and the compound obtained in the above stage 4 (200 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1,57-to 1.67 (3H, m), 1,75-1,80 (2H, m), 1,88-of 1.92 (2H, m), 2,13 (1H, d, J=13.3 Hz), 2,32-is 2.37 (2H, m), 2,48-2,52 (2H, user. m), 3,24 (1H, user. C)3,37 (3H, s), 3,44 (1H, d, J=12,4 Hz), 3,71-of 3.77 (1H, m), 3,90 (1H, DD, J=14,7, and 7.8 Hz), 4.04 the-4,10 (2H, m), 6,06-6,09 (1H, m), 6,58-6,60 (1H, m), 7,40 (1H, d, J=1,8 Hz), 7,68 (1H, s), 8,08 (1H, s)8,28 (1H, s), and 8.50 (1H, s), 9,24 (1H, s).

Stage 6

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

Specified in the title compound (55 mg) was obtained as a pale yellow solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 5 (210 mg).

MS (ESI) m/z: 380 (MH) +.

1H-NMR (DMSO-d6) δ: 1.41 to a 1.45 (1H, m)and 1.51-of 1.64 (2H, m), 1,90-of 1.94 (1H, m), 3,15-3,17 (1H, m), 3,20 (3H, s), 3,31-to 3.35 (1H, m), 3,71 of 3.75 (1H, m), 3,81-to 3.89 (2H, m), 3,92-of 3.97 (1H, m), 6,51 (1H, DD, J=3,4, and 2.3 Hz), 7,53 (1H, t, J=2,9 Hz), 7,83 (1H, d, J=1.7 Hz), 8,23 (2H, t, J=1.7 Hz), charged 8.52 (1H, d, J=2.3 Hz), 11,60 (1H, s), 11,74 (1H, s).

(Example 114)

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

and its enantiomer

Stage 1

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-DL-threo-Gex-5-Anita

2-[(Benzyloxy)methyl]-2,3-dihydro-4H-Piran-4-one obtained by the method described in WO 2001/019831 (1,36 g), and chloralhydrate cerium(III) (2,31 g) was dissolved in ethanol (26 ml) and methylene chloride (52 ml). Then the atmosphere was replaced with nitrogen, the mixture was cooled to -78°C was added a suspension of sodium borohydride (259 mg) in ethanol (26 ml). After stirring at -78°C for 90 minutes was added a saturated aqueous solution of sodium bicarbonate. The mixture was heated to room temperature and then filtered through celite. The filtrate was extracted with ethyl acetate three times. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (1,34 g) in the form of oil coric is avago color.

1H-NMR (CDCl3) δ: 1,75-to 1.77 (2H, m), 2,17-of 2.23 (1H, m), 3,62 (2H, DQC, J=23,2, 5,1 Hz), 4,16-4,22 (1H, m), 4,40-to 4.41 (1H, m), 4,60 (2H, s), 4,79 (1H, DQC, J=6,2, 1.2 Hz), 6,41 (1H, DD, J=6,2, 1.2 Hz), 7,29-7,34 (6H, m).

Stage 2

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-DL-threo-hexitol

The compound obtained in the above stage 1 (1,33 mg), was dissolved in ethanol (1 ml) was added 10% palladium on coal. The mixture was stirred in hydrogen atmosphere at room temperature for 3 hours. The reaction solution was filtered through celite and the filtrate was concentrated. Then the residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.22 g) as a colourless oil.

1H-NMR (CDCl3) δ: of 1.26 to 1.34 (1H, m), 1,48 is 1.58 (2H, m), 1,86-of 1.95 (2H, m), 3,40-to 3.58 (4H, m), 3,79-3,82 (1H, m), 4,07 (1H, DDD, J=11.8 in, 2,2, 1,1 Hz), 4,58 (2H, DD, J=19,9, 12.1 Hz), 7,26-7,37 (5H, m).

Stage 3

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-4-O-methyl-DL-threo-hexitol

Specified in the title compound (569 mg) was obtained as colorless oil by the method similar to those used in stage 1 of example 63, using the compound obtained in the above stage 2 (546 mg).

1H-NMR (CDCl3) δ: 1,19 of 1.28 (1H, m), 1,45-1,50 (1H, m), 1,92-2,02 (2H, m), 3,31 is 3.57 (5H, m)to 3.35 (3H, s), 4.09 to (1H, DDD, J=11,7, a 4.9, 1.7 Hz), 4,58 (2H, DD, J=34,9, 17.5 Hz), 7,26 and 7.36 (5H, m).

Stage 4

1.5-Anhydrous-2,4-dideoxy-3-O-methyl-DL-threo-hexitol

Connection, receiving the Noah above stage 3 (561 mg), was dissolved in ethanol (3 ml) was added 20% palladium hydroxide. The mixture was stirred in hydrogen atmosphere at room temperature for 21 hours. The reaction solution was filtered through celite and washed with ethanol and the filtrate was concentrated. The oil was dissolved in ethyl acetate and the solution was filtered through a cotton filter. Thereafter, the filtrate was concentrated to obtain specified in the title compound (337 mg) as a colourless oil.

1H-NMR (CDCl3) δ: 1,22 (1H, DD, J=23,4, and 11.4 Hz), 1,42-of 1.52 (1H, m), 1.91 a is 2.00 (2H, m), is 2.09 (1H, user. C)3,19-3,47 (3H, m)to 3.36 (3H, s), 3,57-3,61 (2H, m), 4,08 (1H, DDD, J=11,6, a 4.9, 1.5 Hz).

Stage 5

3-Cyclohex-1-EN-1-yl-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (1.39 g) was obtained in a way similar to stage 3 of example 1, using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (1,83 g) and the compound obtained in stage 2 of example 35 (2.00 d).

MS (APCI) m/z: 332 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,65 was 1.69 (2H, m), 1,75-of 1.81 (2H, m), 2,23-of 2.24 (2H, m), 2,39-2,39 (2H, m), 5,93-5,94 (1H, m), 6,51 (1H, DD, J=3,4, 2.0 Hz), 7,52-7,53 (1H, m), 7,56 (1H, d, J=2.0 Hz), 8,19 (1H, d, J=2.0 Hz), 8,24 (1H, d, J=2.0 Hz), 8,48 (1H, d, J=2.2 Hz), 11,27 (1H, user. C)11,74 (1H, user. C).

Stage 6

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-DL-threo-hexitol

is iroe specified in the title compound was obtained by way similar to the one used in stage 3 of example 35 using the compound obtained in the above stage 4 (88 mg)and the compound obtained in the above stage 5 (133 mg).

MS (APCI) m/z: 460 [M+H]+.

Stage 7

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

Specified in the title compound (41 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 7.

MS (APCI) m/z: 380 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,08 (1H, DD, J=11,4, 5.7 Hz), 1,20-1,24 (2H, m), 1,84-to 1.87 (1H, user. m), 2,03-2,05 (1H, user. m), up 3.22 (3H, s), 3,67 at 3.69 (1H, user. m), 3,83-3,88 (2H, m), of 3.97 (1H, DD, J=14,2, and 7.8 Hz), 6,50 (1H, DD, J=3,4, and 1.6 Hz), 7,51 (1H, t, J=3.0 Hz), 7,79 (1H, d, J=1,8 Hz), 8,21 (2H, DD, J=4,4, 2,1 Hz)and 8.50 (1H, d, J=2.3 Hz), 11,70 (1H, user. C).

(Example 115)

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(CIS-4-methoxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-1-[(CIS-4-methoxycyclohexyl)methyl]-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (224 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in stage 2 of example 99 (300 mg).

1H-NMR (CDCl3) δ: of 1.36 (12H, s), 1.41 to the 1.44 (6H, m), of 1.73 to 1.76 (2H, m), 1,8-of 1.88 (2H, m), 1,92-of 1.94 (3H, m), 2,30 of-2.32 (2H, m), 2,43 is 2.44 (2H, m), and 3.31 (3H, s), 3,42 is-3.45 (1H, m), 3,71 (2H, d, J=7,3 Hz), 6,01-of 6.02 (1H, m), of 7.48 (1H, d, J=1.5 Hz), 8,43 (1H, d, J=1.5 Hz).

Stage 2

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1-[(CIS-4-methoxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (145 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 35 (167 mg)and the compound obtained in the above stage 1 (224 mg).

MS (ESI) m/z: 492 (M+H)+.

1H-NMR (CDCl3) δ: 1,34-of 1.55 (6H, m), 1,73-to 1.82 (2H, m), 1,86 is 2.01 (5H, m), 2,29-of 2.38 (2H, m), 2,46-of 2.54 (2H, m), 3,30 (3H, s), 3,41-3,47 (1H, m), with 3.79 (2H, d, J=7,3 Hz), 6,05-6,11 (1H, m), of 7.36 (2H, d, J=2,8 Hz), 7,38 (2H,, d, J=1,8 Hz), 8,07 (1H, d, J=1,8 Hz), of 8.27 (1H, d, J=1,8 Hz), 8,53 (1H, d, J=1,8 Hz), 8,81 (1H, user. C).

Stage 3

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(CIS-4-methoxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (87 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (143 mg).

HRMS (ESI) [M+H]+calculated: C21H23ClN5O2412,15403; found: 412,15085.

1H-NMR (DMSO-d6) δ: 1,27-of 1.40 (7H, m), 1,73-of 1.85 (2H, m), 1,87-to 1.98 (1H, m), 3,19 (3H, in), 3.75 (2H, d, J=7,4 Hz), 7,74 (1H, d, J=2,9 Hz), 7,95 (1H, d, J=2.3 Hz), 8,18 (1H, d, J=2.3 Hz), of 8.27 (1H, d, J=1.7 Hz), 8,64 (1H, d, J=1.7 Hz), to 11.61 (1H, s), 12,09 (1H, user. C).

(Example 116)

-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(CIS-4-hydroxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

1-[(CIS-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)methyl]-3-cyclohex-1-EN-1-yl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (288 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in stage 2 of example 102 (400 mg).

1H-NMR (CDCl3) δ: 0,03 (6H, s)to 0.89 (9H, s)of 1.36 (12H, s), 1,40 was 1.43 (4H, m), 1,54-and 1.54 (2H, m), 1,65-to 1.77 (4H, m), 1,84-1,90 (3H, m), 2,28 is 2.33 (2H, m), 2,42 is 2.46 (2H, m), of 3.73 (2H, d, J=7,6 Hz), 3,94-of 3.96 (1H, m), 6,00-of 6.02 (1H, m), of 7.48 (1H, d, J=1.2 Hz), 8,43 (1H, d, J=1.2 Hz).

Stage 2

1-[(CIS-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)methyl]-6-(3-chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (116 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 35 (143 mg)and the compound obtained in the above stage 1 (245 mg).

1H-NMR (CDCl3) δ: 1,34-of 1.55 (6H, m), 1,73-to 1.82 (2H, m), 1,86 is 2.01 (5H, m), 2,29-of 2.38 (2H, m), 2,46-of 2.54 (2H, m), 3,30 (3H, s), 3,41-3,47 (1H, m), with 3.79 (2H, d, J=7,3 Hz), 6,05-6,11 (1H, m), of 7.36 (2H, d, J=2,8 Hz), 7,38 (2H,, d, J=1,8 Hz), 8,07 (1H, d, J=1,8 Hz), of 8.27 (1H, d, J=1,8 Hz), 8,53 (1H, d, J=1,8 Hz), 8,81 (1H, user. C).

Stage 3

6-(3-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(CIS-4-hydroxycyclohexyl)methyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the header is VCE compound (34 mg) was obtained by way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (115 mg).

HRMS (ESI) [M+H]+calculated: C20H21ClN5O2398,13838; found: 398,13773.

1H-NMR (DMSO-d6) δ: 0,99-of 1.15 (2H, m), 1,21-1,49 (4H, m)and 1.51 is 1.70 (2H, m), 1,73-of 1.85 (1H, m), 3,67-of 3.85 (3H, m), 7,74 (1H, d, J=1,8 Hz), the 7.85-of 7.97 (1H, m), 8,16-to 8.20 (1H, m), of 8.27 (1H, d, J=1,8 Hz), 8,64 (1H, d, J=1,8 Hz), to 11.61 (1H, user. C)12,09 (1H, user. C).

(Example 117)

6-(4-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-(4-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (120 mg) was obtained in a way similar to stage 3 of example 1, using 5-bromo-4-chloro-1H-pyrrolo[2,3-b]pyridine (189 mg) and the compound obtained in stage 1 of example 41 (300 mg).

MS (ESI) m/z: 466 (M+H)+.

1H-NMR (CDCl3) δ: 1,73-to 1.82 (2H, m), 1,86 is 1.96 (3H, m), 2,30-2,39 (2H, m), 2,47 is 2.55 (2H, m), 3,37 is-3.45 (1H, m), 3,49 (2H, s), 3,53-3,62 (1H, m), 3,65-of 3.80 (3H, m), 3,86-was 4.02 (3H, m), 6,07-6,12 (1H, m), 6,66-of 6.71 (1H, m), 7,39-the 7.43 (1H, m), 7,56 (1H, d, J=1,8 Hz), 8,16 (1H, d, J=1,8 Hz), of 8.27 (1H, s), 8,91 (1H, user. C).

Stage 2

6-(4-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (71 mg) was obtained in a way similar to when adiya's 6 of example 35, using the compound obtained in the above stage 1 (119 mg).

HRMS (ESI) [M+H]+calculated: C18H17ClN5O3386,10199; found: 386,10206.

1H-NMR (DMSO-d6) δ: 2,42-2,47 (1H, m), 3,37-3,62 (4H, m), 3,66-of 3.97 (4H, m), 6,53-6,59 (1H, m), 7,63-to 7.67 (2H, m), 8,01 (1H, d, J=1,8 Hz), 8,24 (1H, s), 11,72 (1H, user. C)to 12.13 (1H, user. C).

(Example 118)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (144 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (350 mg)and the compound obtained in stage 1 of example 96 (275 mg).

MS (ESI) m/z: 450 (M+H)+.

Stage 2

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (83 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (144 mg).

MS (ESI) m/z: 370 (M+H)+.

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he dimethanesulfonate

To a suspension of the compound obtained in opican the th above stage 2 (83 mg), in chloroform (1.5 ml) was added dropwise methanesulfonyl acid (29 μl). Then was added dropwise methanol until then, until it formed a homogeneous solution. After stirring at room temperature for 30 minutes, the solvent was evaporated under reduced pressure and hexane was added, then stirred. The solid is collected by filtration and dried under reduced pressure over night when heated to 50°C with obtaining specified in the title compound (106 mg).

MS (ESI) m/z: 370 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C18H17FN5O3370,13154; found: 370,13332.

1H-NMR (DMSO-d6) δ: of 2.34 (6H, s), 3,31-to 3.38 (1H, m), 3.43 points of 3.56 (2H, m), 3,61 (1H, d, J=10,9 Hz), 3,70-was 4.02 (5H, m), 7,53-of 7.55 (1H, m), to $ 7.91 (1H, d, J=2.3 Hz), 8,29-8,31 (2H, m), to 8.62 (1H, d, J=2.3 Hz), to 11.61 (1H, user. C)11,68 (1H, user. C).

(Example 119)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (60 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 96 (70 mg)and the compound obtained in stage 1 of example 45 (111 mg).

MS (ESI) m/z: 464 (M+H)+.

1H-NMR (CDCl 3) δ: 1,75-to 1.79 (2H, m), 1,87 is 1.91 (2H, m), 2,31 to 2.35 (2H, m), 2,47 (3H, s), 2,52 is 2.55 (2H, m), 3,39 (1H, DD, J=11,7, 9.5 Hz), 3,53-to 3.58 (1H, m), 3,65-3,70 (2H, m), of 3.73 is 3.76 (1H, m), 3,84-of 3.94 (4H, m), 6,06-between 6.08 (1H, m), 7,14 (1H, t, J=2,6 Hz), 7.23 percent (1H, s), to $ 7.91 (1H, d, J=2.3 Hz), 8,27-8,29 (1H, m), 8,30 (1H, d, J=1.7 Hz).

Stage 2

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (25 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (60 mg).

HRMS (ESI) [M+H]+calculated: C19H19FN5O3384,14719; found: 384,14985.

MS (ESI) m/z: 384 (M+H)+.

1H-NMR (DMSO-d6) δ: of 2.38 (3H, s), 3.27 to and 3.31 (1H, m), 3,41-to 3.52 (2H, m)and 3.59 (1H, d, J=11.5 Hz), 3,68-of 3.80 (3H, m), 3,84-3,93 (2H, m), 7,44 (1H, s), 7,54 (1H, t, J=2.3 Hz), 8,00 (1H, d, J=1.7 Hz), 8,29 (1H, d, J=2.3 Hz), to 11.52 (1H, s), of 11.61 (1H, s).

(Example 120)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridine

5-Bromo-4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine obtained by the method described in Tetrahedron Lett. 45, 2317-2319 (2004) (230 mg)was dissolved in tetrahydrofuran (5.0 ml). Added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (810 μl) and the mixture was stirred at room temperature for one hour. To the reaction solution was added to the ode, then was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (103 mg).

MS (ESI) m/z: 215 (M+H)+.

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (212 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (254 mg)and the compound obtained in the above stage 1 (103 mg).

MS (ESI) m/z: 450 (M+H)+.

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (20 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (212 mg).

MS (ESI) m/z: 370 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C18H17FN5O3370,13154; found: 370,13107.

1H-NMR (DMSO-d6) δ: 3,33-3,62 (4H, m), 3,70-3,97 (5H, m), 6,59-of 6.61 (1H, m), EUR 7.57-to 7.59 (1H, m), 7,74 (1H, s)to 8.12 (1H, s), 8,35-at 8.36 (1H, m), 11,71 (1H, user. C), 12,10 (1H, user. C).

(Example 121)

6-(2,3-Dihydro-1H-pyrrolo[2,3-b]pyridi the-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

3-Cyclohex-1-EN-1-yl-6-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (118 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (319 mg)and 5-bromo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (199 mg).

MS (ESI) m/z: 434 (M+H)+.

Stage 2

6-(2,3-Dihydro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (28 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (118 mg).

MS (ESI) m/z: 354 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C18H20N5O3354,15661; found: 354,15597.

1H-NMR (DMSO-d6) δ: 3.04 from (2H, t, J=8.6 Hz), 3,32-3,62 (6H, m), 3,71-of 3.96 (5H, m), of 6.52 (1H, s), EUR 7.57-to 7.59 (1H, m), 7,66-to 7.67 (1H, m), 8,00 shed 8.01 (1H, m), 8,08 (1H, d, J=2.3 Hz), 11,54 (1H, user. C).

(Example 122)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-4-iodine-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine

To a solution of 5-bromo-4-iodine-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2008/150914 (1,14 g)in N,N-dimethylformamide (12 ml) on l is danoy bath was added 55% sodium hydride (170 mg) and chloride 4-methylbenzenesulfonyl (740 mg) and the mixture was stirred at room temperature for 3 hours. To the reaction solution was added an aqueous solution of ammonium chloride and the precipitated solid substance was collected by filtration and washed with water. This substance was dissolved in dichloromethane and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain specified in the title compound (1.68 g).

1H-NMR (CDCl3) δ: 2,39 (3H, s), 6,51 (1H, d, J=4.0 Hz), 7,26 (2H, d, J=8.6 Hz), 7,79 (1H, d, J=4.0 Hz), of 8.04 (2H, d, J=8.6 Hz), 8,43 (1H, s).

Stage 2

5-Bromo-1-[(4-were)sulfonyl]-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine

Specified in the title compound (168 mg) was obtained in a way similar to stage 1 of example 84 using the compound obtained in the above stage 1 (300 mg).

1H-NMR (CDCl3) δ: 2,39 (3H, s), 6,79-6,84 (1H, m), 7,31 (2H, d, J=8,3 Hz), 7,88 (1H, d, J=4,1 Hz), with 8.05 (2H, d, J=8,3 Hz), to 8.62 (1H, s).

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-{1-[(4-were)sulfonyl]-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (172 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in the above stage 2 (242 mg)and the compound obtained in stage 1 of example 41 (306 mg).

MS (ESI) m/z: 654 (M+H)+.

1H-NMR (CDCl3) δ: 1,68-of 2.54 (8H, m)to 2.41 (3H, s), 3,29-3,99 (9H, m), 6,07-6,11 (1H, m), 6.87 in (1H, s), 7,34 (2H, d, J=7.8 Hz), 7,43-,49 (1H, m)of 7.96 (2H, s)to 8.12 (2H, d, J=8,3 Hz), 8,40 (1H, s).

Stage 4

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-[4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 3 (170 mg)in methanol (2.6 ml) was added 1 N. aqueous sodium hydroxide solution (0,52 ml) and the mixture was stirred at room temperature for 17 hours. The reaction solution was separated by adding an aqueous solution of ammonium chloride and ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (58 mg).

1H-NMR (CDCl3) δ: 1,73-to 1.82 (2H, m), 1,86-of 1.95 (2H, m), 2,29-2,39 (2H, m), 2,46-to 2.57 (2H, m), 3.33 and-4,00 (9H, m), 6,07-6,13 (1H, m), 6,78-6,83 (1H, m), 7,41-the 7.43 (1H, m), 7,54 (1H, s), with 8.05 (1H, d, J=2.0 Hz), 8,29 (1H, s), 9,13 (1H, user. C).

Stage 5

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (17 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (56 mg).

MS (ESI) m/z: 420 (M+H)+.

1H-NMR (DMSO-d6) δ: ,24-3,97 (9H, m), 6,62 is 6.67 (1H, m), 7,55 (1H, s), 7,83 (1H, s), of 7.90 (1H, d, J=1,8 Hz), of 8.27 (1H, s), 11,74 (1H, s), 12,37 (1H, s).

(Example 123)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-ethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-4-ethyl-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine

Into a solution of the compound obtained in stage 1 of example 122 (300 mg)in N,N-dimethylformamide (12 ml) was added to the complex chloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) - dichloromethane (26 mg), potassium carbonate (130 mg) and triethylborane (1 M solution in hexane) (0.75 ml). The mixture was stirred in nitrogen atmosphere at 80°C for 24 hours. The reaction solution was cooled to room temperature and then separated by adding ethyl acetate and distilled water. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (147 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (CDCl3) δ: to 1.21 (3H, t, J=7.5 Hz), of 2.38 (3H, s)to 2.94 (2H, q, J=7.5 Hz), 6,60 (1H, d, J=4,1 Hz), 7,28 (2H, d, J=8,3 Hz), of 7.70 (1H, d, J=4,1 Hz), with 8.05 (2H, d, J=8,3 Hz), 8,43 (1H, s).

Stage 2

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-{4-ethyl-1-[(4-were)sulfonyl]-1H-Pirro is about[2,3-b]pyridine-5-yl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (122 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (145 mg)and the compound obtained in stage 1 of example 41 (183 mg).

MS (ESI) m/z: 614 (M+H)+.

1H-NMR (CDCl3) δ: 1.14 in (3H, t, J=7.5 Hz), 1,72-to 1.82 (2H, m), 1,86-of 1.94 (2H, m), 2,30-is 2.37 (2H, m), 2,39 (3H, s), 2,46-of 2.54 (2H, m), of 2.81 (2H, q, J=7.5 Hz), 3.33 and-to 3.41 (1H, m), 3,49-to 3.58 (1H, m), 3,62 of 3.75 (3H, m), 3,80-3,99 (4H, m), between 6.08 (1H, s), of 6.68 (1H, d, J=4,1 Hz), 7,29-7,34 (3H, m), to 7.77 (1H, d, J=4,1 Hz), of 7.97 (1H, d, J=1.4 Hz), 8,13 (2H, d, J=8,3 Hz), compared to 8.26 (1H, s).

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-ethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (75 mg) was obtained in a way similar to stage 4 of example 122 using the compound obtained in the above stage 2 (120 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1,24 (3H, t, J=7,3 Hz), 1,74-to 1.82 (2H, m), 1,87-of 1.95 (2H, m), 2,31-2,39 (2H, m), 2,48-of 2.56 (2H, m), 2.91 in (2H, q, J=7,3 Hz), 3,35-4,01 (9H, m), 6,07-6,13 (1H, m), 6,59-6,63 (1H, m), 7,34-7,38 (1H, m), 7,39 (1H, d, J=1,8 Hz), of 8.06 (1H, d, J=1,8 Hz), 8,17 (1H, s), of 9.21 (1H, user. C).

Stage 4

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-ethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (27 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (75 is g).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1.14 in (3H, t, J=7.5 Hz), 2,84 (2H, q, J=7.5 Hz), 3.25 to 3,97 (9H, m), 6,56-6,60 (1H, m), 7,47-7,50 (1H, m), 7,51 (1H, d, J=1.4 Hz), 7,88 (1H, d, J=1.4 Hz), of 8.04 (1H, s), 11,66 (2H, s).

(Example 124)

6-(3,4-Dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-3,4-dimethyl-2-(trimethylsilyl)-1H-pyrrolo[2,3-b]pyridine

The compound obtained in stage 1 of example 36 (1.8 g)was dissolved in N,N-dimethylformamide (40 ml) was added potassium acetate (1.7 g) and lithium chloride (0.3 g). After replacing the atmosphere in the system with nitrogen were added palladium acetate (0,13 g) and 1-trimethylsilyl-1-propyne (4.3 ml) and the mixture was stirred at 90°C for three days. The reaction solution was cooled to room temperature and then N,N-dimethylformamide drove away. The obtained residue was diluted with ethyl acetate and then washed with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated to obtain crude compound indicated in heading (2.4 g).

MS (ESI) m/z: 297 (M+H)+.

Stage 2

5-Bromo-3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine

The compound obtained in the above stage 1 (2.4 g)was dissolved in tetrahydrofuran (25 ml). Added 2 M aqueous solution of hydrochloric acid (10 ml) and the mixture was heated under reflux for 18 hours. The reactions the config solution was cooled to room temperature, neutralized with saturated aqueous sodium bicarbonate solution and then was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (0.2 g).

MS (ESI) m/z: 225 (M+H)+.

1H-NMR (CDCl3) δ: 2,46 (3H, s), was 2.76 (3H, s), 7,00 (1H, s), 8,29 (1H, s).

Stage 3

3-Cyclohex-1-EN-1-yl-6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (145 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (306 mg)and the compound obtained in the above stage 2 (142 mg).

MS (ESI) m/z: 460 (M+H)+.

Stage 4

6-(3,4-Dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (135 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (222 mg).

MS (ESI) m/z: 380 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C20H21N5O3380,17226; found: 380,17247.

1H-NMR (DMSO-d6) δ: 2,46 (3H, s), 2,58 (3H, s), 3,29-to 3.33 (1H, m), 3,42-of 3.54 (2H, m), 3,59-3,61 (1H, m), 3,0-and 3.72 (1H, m), 3,76-of 3.95 (4H, m), 7,20 (1H, s), 7,51 (1H, d, J=1.7 Hz), 7,88 (1H, d, J=1.7 Hz), 8,00 (1H, s), 11,27-11,28 (1H, m), 11,64 (1H, s).

(Example 125)

6-(3-Chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine

The compound obtained in stage 3 of example 36 (323 mg)was dissolved in tetrahydrofuran (6 ml). Was added N-chlorosuccinimide (225 mg) and the mixture was stirred at room temperature for three days. To the reaction solution was added water, then was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated to obtain specified in the title compound (364 mg).

MS (ESI) m/z: 245 (M+H)+.

Stage 2

Tert-butyl 5-bromo-3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Specified in the title compound (430 mg) was obtained in a way similar to stage 1 of example 35 using the compound obtained in the above stage 1 (364 mg).

MS (ESI) m/z: 345 (M+H)+.

1H-NMR (CDCl3) δ: of 1.66 (9H, s)2,84 (3H, s), to 7.59 (1H, s), 8,55 (1H, s).

Stage 3

6-(3-Chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (125 mg) was obtained in a way similar to stage 3 note the RA 1, using the compound obtained in stage 1 of example 41 (302 mg)and the compound obtained in the above stage 2 (215 mg).

MS (ESI) m/z: 480 (M+H)+.

Stage 4

6-(3-Chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (77 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (125 mg).

MS (ESI) m/z: 400 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C19H19ClN5O3400,11764; found: 400,12198.

1H-NMR (DMSO-d6) δ: 2,66 (3H, s), 3,28-3,97 (9H, m), 7,55 (1H, d, J=1,8 Hz), 7,66 (1H, d, J=2.7 Hz), to $ 7.91 (1H, d, J=1,8 Hz), 8,13 (1H, s), 11,67 (1H, user. C)12,00 (1H, user. C).

(Example 126)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine

The compound obtained in stage 3 of example 36 (3.0 g)was dissolved in acetonitrile (400 ml) and acetic acid (80 ml). Added selectfluor (7.6 g) and the mixture was heated with stirring at 80°C for 15 hours. The reaction solution was cooled to room temperature, concentrated, diluted with ethyl acetate and sequentially washed with saturated aqueous sodium bicarbonate and saturated saline solution. PEFC is drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-chloroform) to obtain the specified title compound (2.0 g).

MS (ESI) m/z: 229 (M+H)+.

1H-NMR (CDCl3) δ: 2,71 (3H, d, J=2.7 Hz),? 7.04 baby mortality (1H, d, J=2.3 Hz), a 8.34 (1H, d, J=2.3 Hz), 8,76 (1H, user. C).

Stage 2

Tert-butyl 5-bromo-3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Specified in the title compound (1.2 g) was obtained by the method similar to those used in stage 1 of example 35 using the compound obtained in the above stage 1 (2.0 g).

1H-NMR (CDCl3) δ: 1,65 (9H, s)to 2.67 (3H, s), of 7.36-7,37 (1H, m), 8,54 (1H, s).

Stage 3

3-Cyclohex-1-EN-1-yl-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (237 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 41 (290 mg)and the compound obtained in the above stage 2 (180 mg).

MS (ESI) m/z: 464 (M+H)+.

Stage 4

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (68 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (237 mg).

MS (ESI) m/z: 384 (M+H)+.

HRMS (ESI) [(M+H) ] calculated: C19H19FN5O3384,14719; found: 384,14806.

1H-NMR (DMSO-d6) δ: to 2.55 (3H, s), 3,28-3,62 (4H, m), 3,69-of 3.96 (5H, m), 7,44-7,47 (1H, m), 7,56-EUR 7.57 (1H, m), 7,92 (1H, d, J=1.4 Hz), 8,13 (1H, s), of $ 11.48 (1H, user. C)11,67 (1H, s).

(Example 127)

6-(6-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

{1-[(2S)-1,4-Dioxane-2-ylmethyl]-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-yl}boronic acid

Specified in the title compound (2.2 g) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in stage 1 of example 41 (5.0 g).

MS (ESI) m/z: 280 (M+H)+.

Stage 2

6-(6-Chloro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (107 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (75 mg)and the compound obtained in stage 5 of example 78 (68 mg).

MS (ESI) m/z: 386 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C18H17ClN5O3386,10199; found: 386,10355.

1H-NMR (DMSO-d6) δ: 3,32-3,62 (4H, m), 3,67-3,97 (5H, m), is 6.54 (1H, s), EUR 7.57-of 7.60 (1H, m), 7,62-the 7.65 (1H, m), of 7.96-to 7.99 (1H, m), 8,05-8,07 (1H, m), 11,70 (1H, user. C)11,96 (1H, user. C).

(Example 128)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(7-fluoro-4-methyl-1H-indol-5-yl)-1,3-Digi the ro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

4-Bromo-6-fluoro-2-iodine-3-methylaniline

Specified in the title compound (6.9 g) was obtained by the method similar to those used in stage 1 of example 36 using 4-bromo-6-fluoro-3-methylaniline (5.0 g).

MS (ESI) m/z: 330 (M+H)+.

Stage 2

4-Bromo-6-fluoro-2-[(trimethylsilyl)ethinyl]-3-methylaniline

Specified in the title compound (6.9 g) was obtained in a way similar to step 2 of example 36 using 4-bromo-6-fluoro-2-iodine-3-methylaniline obtained in the above stage 1 (6,9 g).

MS (ESI) m/z: 300 (M+H)+.

Stage 3

5-Bromo-7-fluoro-4-methyl-1H-indol

Specified in the title compound (3.0 g) was obtained in a way similar to stage 3 of example 36, using the compound obtained in the above stage 2 (6,9 g).

MS (ESI) m/z: 228 (M+H)+.

1H-NMR (CDCl3) δ: 2,54 (3H, s), 6,57-6,59 (1H, m), 7,11 (1H, d, J=10.3 Hz), 7.23 percent (1H, t, J=2,9 Hz), scored 8.38 (1H, user. C).

Stage 4

6-(6-Fluoro-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (109 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 1 of example 127 (108 mg)and the compound obtained in the above stage 3 (80 mg).

MS (ESI) m/z: 383 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C20H20FN4Osub> 3383,15194; found: 383,15248.

1H-NMR (DMSO-D6) δ: 2,39 (3H, s), 3,31-3,97 (9H, m), is 6.61 (1H, s), 6.87 in (1H, d, J=10,9 Hz), 7,44-7,46 (1H, m), 7,51 (1H, s), 7,89-of 7.90 (1H, m), of 11.61 (1H, user. C), 11,65 (1H, user. C).

(Example 129)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(6-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (0.8 g) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in stage 1 of example 40 (1.4 g).

MS (ESI) m/z: 314 (M+H)+.

1H-NMR (DMSO-d6) δ: 3,26 of 3.28 (1H, m), 3.45 points-to 3.49 (2H, m), 3,59-3,62 (1H, m), 3,70-to 3.89 (5H, m), of 7.75 to 7.75 (1H, m), 8,00-8,00 (1H, m), to 11.79 (1H, user. C).

Stage 2

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(6-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (11 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained by the method described in WO 2007/135398 (69 mg)and the compound obtained in the above stage 1 (50 mg).

MS (ESI) m/z: 366 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H19N5O3366,15661; found: 366,15746.

1H-NMR (DMSO-d6) δ: 2,48 (3H, s), 3,39-3,94 (9H, m), 6.42 per (1H, d, J=3,24 Hz), 7,41-7,42 (1H, m), 7,56 (1H, d, J=1,84 Hz), 7,78 (1H, s), to $ 7.91 (1H, d, J=1,84 Hz), 11,53 (1H, s), 11,63 (1H, s).

(Example 130)

6-(4-Amino-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

4 Azido-5-bromo-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine

Specified in the title compound (299 mg) was obtained in a way similar to stage 1 of example 122 using 4-azido-5-bromo-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2008/150914 (199 mg).

1H-NMR (CDCl3) δ: 2,39 (3H, s), 6,85 (1H, d, J=4.0 Hz), 7,29 (2H, d, J=8,3 Hz), 7,73 (1H, d, J=4.0 Hz), of 8.04 (2H, d, J=8,3 Hz), 8,39 (1H, s).

Stage 2

5-Bromo-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-4-amine

Into a solution of the compound obtained in the above stage 1 (275 mg)in 2-propanol (14 ml) in an ice bath was added sodium borohydride (27 mg) and the mixture was stirred at room temperature for 4 hours. The reaction solution was separated by adding an aqueous solution of ammonium chloride and ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (141 mg).

MS (ESI) m/z: 367 (M+H)+.

1H-NMR (DMSO-d6) δ: of 2.34 (3H, s), 6,79 (2H, user. C), 6,97 (1H, d, J=4.0 Hz), 7,40 (2H, the, J=8.0 Hz), EUR 7.57 (1H, d, J=4.0 Hz), to $ 7.91 (2H, d, J=8.0 Hz), 8,03 (1H, s).

Stage 3

6-{4-Amino-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (55 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (50 mg)and the compound obtained in stage 1 of example 127 (57 mg).

MS (ESI) m/z: 521 (M+H)+.

1H-NMR (CDCl3) δ: 2,39 (3H, s), 3.33 and-3,97 (9H, m), 4,51 (2H, s), 6,51 (1H, d, J=4.0 Hz), 7,30 (2H, d, J=8.0 Hz), 7,41 (1H, d, J=1.7 Hz), to 7.59 (1H, d, J=4.0 Hz), 8,04-of 8.06 (2H, m), 8,10 (2H, d, J=8.0 Hz), 9,52 (1H, user. C).

Stage 4

6-(4-Amino-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (16 mg) was obtained in a way similar to stage 4 of example 122 using the compound obtained in the above stage 3 (43 mg).

MS (ESI) m/z: 367 (M+H)+.

1H-NMR (DMSO-d6) δ: 3,38-3,98 (9H, m)5,94 (2H, s), 6,63 (1H, s), 7,08 for 7.12 (1H, m), 7,49-7,53 (1H, m), 7,72 (1H, s), 7,89-to 7.93 (1H, m), 11,17 (1H, s), 11,59 (1H, s).

(Example 131)

6-[4-(Dimethylamino)-1H-pyrrolo[2,3-b]pyridine-5-yl]-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-N,N-dimethyl-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-4-amine

Into a solution of the compound obtained in a hundred is AI 2 of example 130 (64 mg), in N,N-dimethylformamide (3.6 ml) in an ice bath was added 55% sodium hydride (19 mg) and methyliodide (0,027 ml) and the mixture was stirred in an ice bath for 2 hours. The reaction solution was separated by adding an aqueous solution of ammonium chloride and ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (73 mg).

MS (ESI) m/z: 395 (M+H)+.

1H-NMR (CDCl3) δ: of 2.38 (3H, s), of 3.13 (6H, s), 6,74 (1H, d, J=4.0 Hz), 7,25-7,29 (2H, m), EUR 7.57 (1H, d, J=4.0 Hz), of 8.04 (2H, d, J=8.0 Hz), 8,31 (1H, s).

Stage 2

6-{4-(Dimethylamino)-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (48 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (59 mg)and the compound obtained in stage 1 of example 127 (63 mg).

MS (ESI) m/z: 549 (M+H)+.

1H-NMR (CDCl3) δ: 2,39 (3H, s), 2,85 (6H, s), 3,35-3,97 (9H, m), for 6.81 (1H, d, J=4.0 Hz), 7,29 (2H, d, J=8.0 Hz), 7,37 (1H, d, J=1.7 Hz), to 7.61 (1H, d, J=4.0 Hz), 8,03-8,07 (2H, m), 8,10 (2H, d, J=8.0 Hz), 9,37 (1H, user. C).

Stage 3

6-[4-(Dimethylamino)-1H-pyrrolo[2,3-b]pyridine-5-is]-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (15 mg) was obtained in a way similar to stage 4 of example 122 using the compound obtained in the above stage 2 (47 mg).

MS (ESI) m/z: 395 (M+H)+.

1H-NMR (DMSO-d6) δ: 2,84 (6H, s), 3.27 to 3,93 (9H, m), 6,64 is 6.67 (1H, m), 7,28 (1H, s)to 7.50 (1H, d, J=1.7 Hz), the 7.85 (1H, s), to 7.93 (1H, d, J=1.7 Hz), 11,46 (1H, s), 11,57 (1H, s).

(Example 132)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-{4-[(2-hydroxyethyl)(methyl)amino]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

2-[(5-Bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-4-yl)(methyl)amino]ethanol

To 5-bromo-4-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine obtained by the method described in WO 2008/150914 (700 mg), was added 2-(methylamino)ethanol (1.5 ml) and the mixture was heated under reflux at 145°C for 18 hours. The reaction solution was cooled to room temperature and then concentrated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (472 mg).

MS (ESI) m/z: 401 (M+H)+.

1H-NMR (CDCl3) δ: -0,06 (9H, s)of 0.91 (2H, t, J=8,3 Hz), 2,45-of 2.50 (1H, m), 3.04 from (3H, s), 3,50-3,61 (4H, m), 3,74 (2H, s), 5,62 (2H, s), 6,57-6,59 (1H, m), 7,25-7,28 (1H, m), 8,35 (1H, s).

Stage 2

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-[(2-hydroxyethyl)(IU who yl)amino]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (29 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (100 mg)and the compound obtained in stage 1 of example 127 (84 mg).

MS (ESI) m/z: 555 (M+H)+.

1H-NMR (CDCl3) δ: -0,04 (9H, s)to 0.94 (2H, t, J=8,3 Hz), and 2.79 (3H, s), 3,40-4,03 (16H, m), to 5.66 (2H, s), to 6.67 (1H, d, J=3,4 Hz), 7,27 (1H, s), to 7.67 (1H, d, J=1.7 Hz), 8,11 (1H, s), to 8.41 (1H, d, J=1.7 Hz), 11,19 (1H, user. C).

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-{4-[(2-hydroxyethyl)(methyl)amino]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Into a solution of the compound obtained in the above stage 2 (29 mg)in dichloromethane (0.5 ml) was added triperoxonane acid (0.5 ml) and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure. To the obtained residue was added dichloromethane (0.5 ml) and Ethylenediamine (0.2 ml) and the mixture was stirred at room temperature for 7 hours. The reaction solution was separated by adding an aqueous solution of ammonium chloride and chloroform. The obtained organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of methanol-dichloromethane) to obtain specified in the connection header (6 m is).

MS (ESI) m/z: 425 (M+H)+.

1H-NMR (DMSO-d6) δ: 2,74 (3H, s), 3.27 to 3,93 (13H, m), 4,60 (1H, t, J=5.4 Hz), 6,59 (1H, s), 7,28-7,31 (1H, m), 7,70-7,72 (1H, m), 7,89 (1H, s), 7,98 (1H, d, J=1.7 Hz), 11,46 (1H, s), for 11.55 (1H, s).

(Example 133)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-4-methoxy-1H-pyrrolo[2,3-b]pyridine

To a solution of 5-bromo-4-chloro-1H-pyrrolo[2,3-b]pyridine (81 mg) in xylene (3.5 ml) was added potassium methoxide (103 mg), lithium methoxide (27 mg) and tert-butanol (40 ml) and the mixture was heated under reflux at 117°C for 16 hours. The reaction solution was brought to pH 4 by addition of concentrated hydrochloric acid in small portions and separated by adding ethyl acetate and distilled water. The resulting aqueous layer was brought to pH 8 by adding 5 N. aqueous sodium hydroxide solution and was separated by adding ethyl acetate. All the organic layers were collected, washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by thin-layer chromatography (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (20 mg).

MS (ESI) m/z: 227 (M+H)+.

1H-NMR (DMSO-d6) δ: 4,29 (3H, s), 6,77-PC 6.82 (1H, m), 7,37-7,42 (1H, m)to 8.14 (1H, s), 11,82(1H, user. C).

Stage 2

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (26 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 1 (64 mg)and the compound obtained in stage 1 of example 127 (79 mg).

MS (ESI) m/z: 382 (M+H)+.

HRMS (ESI) [M+H]+calculated: C19H20N5O4382,15153; found: 382,15284.

1H-NMR (DMSO-d6) δ: 2,50-2,52 (1H, m), 3,44-of 3.64 (4H, m), 3,67-3,93 (4H, m), 4,19 (3H, s), 6,76-for 6.81 (1H, m), 7,37-7,42 (1H, m), EUR 7.57 (1H, d, J=1,8 Hz), of 7.97 (1H, d, J=1.4 Hz), of 8.04 (1H, s), 11,57 (1H, user. C)11,71 (1H, user. C).

(Example 134)

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-methoxy-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

5-Bromo-1-[(4-were)sulfonyl]-1,2-dihydro-3H-pyrrolo[2,3-b]pyridine-3-one

5-Bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde obtained by the method described in WO 2004/101565 (4,10 g), was dissolved in THF (100 ml). Was added triethylamine (3,05 ml) and p-toluensulfonate (3,82 g) at room temperature and the mixture was stirred over night. The solvent of the reaction mixture is kept under reduced pressure and then diluted with ethyl acetate. After washing with water and saturated saline in this order, the organic layer was dried over what svodnyy sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was led by (dichloromethane-diethyl ether) and then collected by filtration to obtain 5-bromo-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (2,32 g). Then the filtrate was concentrated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain 5-bromo-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (2.55 g). Obtained 5-bromo-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (2.83 g) was dissolved in methylene chloride (50 ml). Added 3-chloroperbenzoic acid (2,13 g) under cooling with ice for 3 hours and the mixture was stirred at room temperature for 2 hours. Then to the reaction solution was added a 10% aqueous solution of sodium sulfite and saturated aqueous sodium bicarbonate solution, then stirred overnight. The reaction solution was diluted with methylene chloride and the insoluble substance was removed by filtration, then was extracted with methylene chloride three times. The obtained organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain from asanoha the title compound (0.18 g) as a solid light red color.

MS (ESI) m/z: 366 (M+H)+.

1H-NMR (CDCl3) δ: 2,42 (3H, s)to 4.41 (2H, s), 7,32 (2H, d, J=7,1 Hz), to 7.99 (2H, d, J=8.5 Hz), 8,02 (1H, d, J=2.7 Hz), 8,64 (1H, d, J=2.0 Hz).

Stage 2

5-Bromo-3-methoxy-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine

The compound obtained in the above stage 1 (110 mg)was dissolved in methanol (5 ml) and tetrahydrofuran (5 ml). Was added dropwise (trimethylsilyl)diazomethane (0.75 ml) under ice cooling and the mixture was stirred at room temperature for 4 hours. Was added dropwise (trimethylsilyl)diazomethane (0.75 ml), then further stirred overnight. To the reaction solution was added acetic acid (154 μl) and then the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (40 mg) as a colourless oil.

MS (ESI) m/z: 381 (M+H)+.

1H-NMR (CDCl3) δ: is 2.37 (3H, s), 3,88 (3H, s), to 7.09 (1H, s), 7,25 (2H, d, J=8.7 Hz), 7.95 is-7,98 (3H, m), to 8.45 (1H, d, J=2.3 Hz).

Stage 3

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-{3-methoxy-1-[(4-were)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-5-yl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (45 mg) was obtained as a pale yellow solid in a way similar to step 2 of example 4, using the compound obtained is as above stage 2 (40 mg), and the compound obtained in stage 1 of example 127 (38 mg).

MS (ESI) m/z: 536 (M+H)+.

Stage 4

1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-methoxy-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (10 mg) was obtained as a pale yellow solid in a way similar to stage 3 of example 84 using the compound obtained in the above stage 3 (45 mg).

HRMS (ESI) [M+H]+calculated: C19H20N5O4382,15153; found: 382,15295.

MS (ESI) m/z: 382 (M+H)+.

1H-NMR (DMSO-d6) δ: 3,31-3,37 (2H, m), 3,44-of 3.54 (2H, m), 3,59-3,62 (1H, m), 3,71-of 3.80 (2H, m), 3,84-of 3.94 (4H, m), 3,97-was 4.02 (1H, m), was 7.08 (1H, d, J=2,9 Hz), 7,87 (1H, d, J=1.7 Hz), 8,16 (1H, d, J=2.3 Hz), of 8.25 (1H, d, J=2.3 Hz), 8,53 (1H, d, J=2.3 Hz), 11,12 (1H, d, J=1.7 Hz), to 11.61 (1H, s).

(Example 135)

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol

Stage 1

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-5-O-methyl-D-threo-hexitol

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

The compound obtained in stage 4 of example 113 (0,86 g), optically analyzed using HPLC with getting listed in the title compounds, D-isomer (isomer A: 0.35 g) and L is the Zomer (isomer B: 0.36 g), respectively.

Column: CHIRALPAK AD (5×50 cm)

Eluent: 25% isopropanol/n-hexane

Flow rate: 25 ml/min

The time of elution: isomer A: 56 min, isomer B: 71 min

Stage 2

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-D-threo-hexitol

Specified in the title compound (220 mg) was obtained as a pale yellow oil in a way similar to step 2 of example 4, using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (173 mg) and D-isomer obtained in the above stage 1 (isomer A, 200 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1,57-of 1.66 (3H, m), 1,75-1,80 (2H, m), 1,88-of 1.92 (2H, m), 2,11-and 2.14 (1H, m), 2,32-of 2.36 (2H, m), 2.49 USD is 2.51 (2H, m), 3,23 (1H, s)to 3.36 (3H, s), 3,44 (1H, DD, J=12,6, 1.1 Hz), 3.72 points-of 3.77 (1H, m)to 3.89 (1H, DD, J=14,6, 7,7 Hz), Android 4.04-4.09 to (2H, m), 6,07-between 6.08 (1H, m), 6,58-6,59 (1H, m), 7,39-7,40 (1H, m), to 7.67 (1H, d, J=2.2 Hz), 8,08 (1H, d, J=1.7 Hz), of 8.27 (1H, d, J=1.7 Hz), and 8.50 (1H, d, J=2.2 Hz), of 9.30 (1H, s).

Stage 3

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol

Specified in the title compound (55 mg) was obtained as a pale yellow solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (220 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,40-1,45 (1H, m), 1,54-of 1.65 (3H, m), 1,89-,95 (1H, m), 3,15-3,18 (1H, m), 3,20 (3H, s), 3,70 is 3.76 (1H, m), 3,80-3,98 (2H, m), 6,51 (1H, DD, J=3.2, and 1.8 Hz), 7,52-7,53 (1H, m), 7,83 (1H, d, J=1,8 Hz), 8,23 (2H, s), charged 8.52 (1H, d, J=2.2 Hz), 11,59 (1H, s), 11,74 (1H, s).

(Example 136)

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (220 mg) was obtained as a pale yellow oil in a way similar to step 2 of example 4, using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (173 mg) and L-isomer obtained in stage 1 of example 135 (isomer B, 200 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1,57-of 1.66 (3H, m), 1,75-1,80 (2H, m), 1,88-of 1.95 (2H, m), 2,11-to 2.15 (1H, m), 2,32 to 2.35 (2H, m), 2,49-2,52 (2H, m), 3,22-3,24 (1H, m)to 3.36 (3H, s), 3,44 (1H, DD, J=12,6) and 1.7 Hz), 3.72 points is 3.76 (1H, m)to 3.89 (1H, DD, J=14,8, 8.0 Hz), Android 4.04-4.09 to (2H, m), 6,06-between 6.08 (1H, m), 6,59 (1H, DD, J=3,7, 2.0 Hz), 7,39 (1H, DD, J=3,4 and 2.2 Hz), to 7.67 (1H, d, J=2.2 Hz), 8,08 (1H, d, J=1.7 Hz), of 8.27 (1H, d, J=2.2 Hz), and 8.50 (1H, d, J=the 2.2 Hz), 9,13 (1H, s).

Stage 2

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title compound (79 mg) was obtained as a pale yellow solid in a way similar to what Tadei 6 of example 35, using the compound obtained in the above stage 1 (220 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,40-of 1.44 (1H, m), 1,54-of 1.64 (2H, m), 1,89-of 1.95 (1H, m), 3,20 (3H, s), 3,71-of 3.77 (1H, m), 3,80-3,98 (3H, m), 6,51 (1H, DD, J=3,4, and 1.6 Hz), 7,52-rate of 7.54 (1H, m), 7,83 (1H, d, J=1,8 Hz), by 8.22-8,23 (2H, m), charged 8.52 (1H, d, J=2.2 Hz), 11,59 (1H, s), 11,74 (1H, s).

(Example 137)

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-L-threo-hexitol

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-D-threo-hexitol

The compound obtained in stage 2 of example 114, optical analyzed using HPLC with getting listed in the title compounds, L-isomer (isomer A: 0,47 g) and D-isomer (isomer B: 0,47 g), respectively.

Preparative separation

Column: CHIRALCEL OD (5×50 cm)

Eluent: 25% isopropanol/n-hexane

Flow rate: 25 ml/min

The time of elution: isomer A: 48 min, isomer B: 58 min

Analysis

Column: CHIRALCEL OD (0,46×5 cm)

Eluent: 10% isopropanol/n-hexane

Flow rate: 1.0 ml/min

The time of elution: isomer A: 12 min, isomer B: 16 min

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-D-threo-hexitol received from a known derivative of sugar in accordance with the following reference example.

The result of analysis by chiral HPLC

The elution time: 16 min

Based on the above result isomer B isomer A were identified as the D-isomer and L-isomer, respectively.

Reference example 1

2,6-Anhydrous-4-O-benzoyl-1-O-benzyl-3-chloro-3,5-dideoxy-D-arabino-hexitol

To a solution of 1,5-anhydrous-3-O-benzoyl-6-O-benzyl-2-deoxy-D-arabino-hexitol obtained by the method described in J. Org. Chem. 67. 3346-3354 (2002) (94 mg)in pyridine (27 mg) under ice cooling was added sulphonylchloride (29 μl) and the mixture was stirred at room temperature for 4 hours. Added water, then was extracted with ethyl acetate. Next, the organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (27 mg).

1H-NMR (CDCl3) δ: 1,82-to 1.87 (1H, m), 2,32-to 2.42 (1H, m), 3,60-and 3.72 (3H, m), 3,84-3,88 (1H, m), 4,13-4,18 (1H, m), to 4.52-to 4.62 (3H, m), 5,26-5,31 (1H, m), 7,27-7,38 (5H, m), 7,44-of 7.48 (2H, m), EUR 7.57-of 7.60 (1H, m), 8.07-a of 8.09 (2H, m,).

Reference example 2

2,6-Anhydrous-4-O-benzoyl-1-O-benzyl-3,5-dideoxy-D-threo-hexitol

Into a solution of the compound obtained in the above referential example 1 (27 mg)in benzene (1.0 ml) was added to the anti-hydride (24 μl) and azobisisobutyronitrile (6 mg) and the mixture was heated under reflux for one hour. Additionally EXT is ulali the anti-hydride (24 μl) and azobisisobutyronitrile (1 mg) and the mixture was heated under reflux for one hour. The reaction solution was concentrated and then the residue was purified by thin-layer chromatography (elwira a mixture of ethyl acetate-hexane) to obtain specified in the title crude compound (35 mg).

MS (ESI) m/z: 327 (M+H)+.

Reference example 3

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-D-threo-hexitol

Into a solution of the compound obtained in the above reference example 2 (35 mg)in methanol (1.0 ml) was added dropwise a solution of sodium methoxide in methanol (5 M, 14 ml) and the mixture was stirred at room temperature for 6 hours. Was added a saturated aqueous solution of sodium bicarbonate, then extracted with ethyl acetate. Then the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (10 mg).

1H-NMR (CDCl3) δ: 1,30 (1H, DD, J=22,9, and 11.5 Hz), 1,49-of 1.57 (1H, m), 1,86-of 1.94 (2H, m), 3,41 is 3.57 (4H, m), of 3.77-a 3.83 (1H, m), 4,05-4,08 (1H, m), 4,55 (2H, d, J=11,6 Hz), 4,60 (1H, d, J=11,6 Hz), 7,27-7,31 (1H, m), 7,33-to 7.35 (4H, m).

Stage 2

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-4-O-methyl-L-threo-hexitol

Specified in the title compound (322 mg) was obtained in a way similar to stage 1 of example 63, using the L-isomer obtained in vysheukazannye 1 (isomer A: 466 mg).

MS (ESI) m/z: 237 (M+H)+.

Stage 3

1.5-Anhydrous-2,4-dideoxy-3-O-methyl-L-threo-hexitol

Specified in the title compound (180 mg) was obtained in a way similar to stage 4 of example 114, using the compound obtained in the above stage 2 (322 mg).

Stage 4

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (1.01 g) was dissolved in tetrahydrofuran (10 ml). After replacing the atmosphere by nitrogen, the solution was cooled with ice. Was added 55% sodium hydride (216 mg) and the mixture was stirred under ice cooling for 20 minutes. Next was added [2-(chloromethoxy)ethyl](trimethyl)silane (875 μl) and the mixture was stirred at room temperature for a period of 15.5 hours. The reaction solution was diluted with water, neutralized 1 N. hydrochloric acid (0,85 ml) and was extracted with ethyl acetate three times. The organic layer was once washed with water and then saturated saline solution and dried over anhydrous sodium sulfate and the solvent was evaporated. The brown oil was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain specified in the connection header (691 mg) as a colourless oil.

MS (APCI) m/z: 375 [M+H]+.

1H-NMR (CDCl3) δ: -0,08 (9H, s), 0,87-of 0.91 (2H, m)to 1.37 (2H, C), 3,49-3,55 (2H, m), 5,70 (2H, s), of 6.52 (1H, d, J=3,7 Hz), 7,32 (1H, d, J=3,7 Hz), 8,35 (1H, d, J=1.6 Hz), 8,69 (1H, d, J=1.6 Hz).

Stage 5

6-Bromo-3-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Ethyl 6-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate, obtained in the conditions described in WO 2008/051493 (2,01 g), was dissolved in tetrahydrofuran (40 ml) was added [2-(chloromethoxy)ethyl](trimethyl)silane (1,37 ml). After replacing the atmosphere by nitrogen, the mixture was cooled with ice. Was added 55% sodium hydride (337 mg) and the mixture was stirred for 50 minutes with gradual warming to room temperature. The reaction solution was extracted three times by adding water and ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate and the solvent was evaporated. The resulting brown oil was dissolved in tetrahydrofuran (40 ml). After cooling, ice was added Isopropylamine (0.9 ml) and the mixture was directly stirred for one hour. After removal of the solvent of the reaction mixture the residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.56 g) as a colourless crystalline substance.

MS (APCI) m/z: 344 [M+H]+.

1H-NMR (CDCl3) δ: -0,02 (9H, s), 0,98-0,99 (2H, m), 3,70-3,74 (2H, m), 5,41 (2H, s)to 7.50 (1H, d, J=2.3 Hz), 8,16 (1H, is, J=2.3 Hz), 10,08 (1H, user. C).

Stage 6

3-{[2-(Trimethylsilyl)ethoxy]methyl}-6-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (195 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 4 (216 mg)and the compound obtained in the above stage 5 (145 mg).

MS (APCI) m/z: 512 [M+H]+.

1H-NMR (CDCl3) δ: -0,05 (9H, s), of 0.01 (9H, s), 0,91-to 0.96 (2H, m), 0,99-of 1.05 (2H, m), 3,56-3,61 (2H, m), 3.75 to of 3.80 (2H, m), 5,49 (2H, s)5,72 (2H, s), 6,59 (1H, d, J=3,7 Hz), 7,42 (1H, d, J=3,7 Hz), 7,55 (1H, d, J=2,3 Hz), with 8.05 (1H, d, J=2.3 Hz), with 8.33 (1H, d, J=2.3 Hz), charged 8.52 (1H, d, J=2.3 Hz), 9,40 (1H, user. C).

Stage 7

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-3-{[2-(trimethylsilyl)ethoxy]methyl}-6-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

The compound obtained in the above stage 6 (130 mg)and the compound obtained in the above stage 3 (60 mg), was stirred at room temperature for 55 minutes in a way similar to stage 3 of example 35, and then the reaction solution was cooled with ice. Was added triethylamine (86 μl) and methanesulfonamide (35 μl) and the mixture was stirred under ice cooling for 30 minutes. Added acetonitrile (6 ml) and potassium carbonate (70 mg) and the mixture was stirred at 8°C for 42 hours. The reaction solution was filtered and washed with acetonitrile and then the filtrate was concentrated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (114 mg) as a colourless oil.

MS (APCI) m/z: 640 [M+H]+.

Stage 8

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol dimethanesulfonate

The compound obtained in the above stage 7 (109 mg)was dissolved in tetrahydrofuran (3 ml). Added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (1.7 ml) and the mixture was stirred at 80°C for 13 hours. The solvent of the reaction mixture is kept off. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-ethanol) and then purified, elwira 5% aqueous mixture of ammonia/ethanol, using PoraPakTMRxn CX (2 g). The obtained crystalline material was dissolved in dichloromethane (3 ml)/ethanol (0.5 ml) was added methanesulfonyl acid (22 μl). The mixture was stirred at room temperature for 15 minutes and then the solvent was evaporated. The residue was led from ethyl acetate and collected by filtration in a nitrogen atmosphere to obtain specified in the title compound (27 mg).

MS (APCI) m/z: 380 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,04-,13 (1H, m), 1,15-of 1.27 (1H, m), 1,82-1,90 (1H, m), 2.00 in of 2.08 (1H, m)2,44 (6H, s), 3,18-to 3.38 (2H, m), up 3.22 (3H, s), 3,64-to 3.73 (1H, user. m), 3,82-3,91 (2H, user. m), 3,98 (1H, DD, J=14,7, and 7.8 Hz), 6,76 (1H, DD, J=3,7, 1.8 Hz), 7,74 (1H, t, J=2.7 Hz), of 7.90 (1H, d, J=1,8 Hz), 8,30 (1H, d, J=1,8 Hz), 8,72 (2H, s), 12,46 (1H, user. C).

(Example 138)

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol

Stage 1

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-4-O-methyl-D-threo-hexitol

Specified in the title compound (340 mg) was obtained in a way similar to stage 1 of example 63, using the D-isomer, is obtained in stage 1 of example 137 (isomer B: 468 mg).

MS (ESI) m/z: 237 (M+H)+.

Stage 2

1.5-Anhydrous-2,4-dideoxy-3-O-methyl-D-threo-hexitol

Specified in the title compound (195 mg) was obtained in a way similar to stage 4 of example 114, using the compound obtained in the above stage 1 (340 mg).

Stage 3

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-3-{[2-(trimethylsilyl)ethoxy]methyl}-6-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol

The compound obtained in the above stage 2 (60 mg), was dissolved in ethyl acetate (6 ml). Was added triethylamine (86 μl) and methanesulfonamide (35 μl) and the mixture was stirred under ice cooling for 30 minutes. The precipitate was removed is by filtration. After washing the ethyl acetate filtrate was concentrated. Added acetonitrile (6 ml), N,N-dimethylformamide (2 ml), the compound obtained in stage 6 of example 137 (130 mg), and potassium carbonate (70 mg) and the mixture was stirred at 80°C for 35 hours. The reaction solution was filtered and washed with acetonitrile and then the filtrate was concentrated. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (128 mg) as a colourless oil.

MS (APCI) m/z: 640 [M+H]+.

1H-NMR (CDCl3) δ: -0,04 (9H, s)0,00 (9H, s), 0,91-to 0.96 (2H, m), 0,98-of 1.03 (2H, m), 1,19-of 1.29 (1H, m)of 1.44 (1H, DDD, J=23,3, 12,4, 4.6 Hz), 1,90-of 1.97 (1H, m), 2,14-of 2.21 (1H, m), 3,29-3,39 (2H, m)to 3.36 (3H, s), 3,57-3,62 (2H, m), 3,65-of 3.78 (3H, m)to 3.92 (1H, DD, J=14,8, and 7.8 Hz), 3,99 (1H, DD, J=11,4, 4.6 Hz), 4,07 (1H, DD, J=14,8, 2.7 Hz), vs. 5.47 (2H, s), 5,74 (2H, s), 6,60 (1H, d, J=3,7 Hz), the 7.43 (1H, d, J=3,7 Hz), to 7.61 (1H, d, J=1,8 Hz), of 8.09 (1H, d, J=1,8 Hz), 8,29 (1H, d, J=1,8 Hz), charged 8.52 (1H, d, J=1,8 Hz).

Stage 4

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol dimethanesulfonate

Specified in the title compound (24 mg) was obtained in a way similar to stage 8 of example 137, using the compound obtained in the above stage 3 (121 mg).

MS (APCI) m/z: 380 [M+H]+.

1H-NMR (DMSO-d6) δ: 1,04-of 1.13 (1H, m), 1,15-of 1.27 (1H, m), 1,82-1,90 (1H, m), 2.00 in of 2.08 (1H, m)2,44 (6H, s), 3,18-to 3.38 (2H, m), up 3.22 (3H,s), 3,64-to 3.73 (1H, user. m), 3,82-3,91 (2H, user. m), 3,98 (1H, DD, J=14,7, and 7.8 Hz), 6,76 (1H, DD, J=3,7, 1.8 Hz), 7,74 (1H, t, J=2.7 Hz), of 7.90 (1H, d, J=1,8 Hz), 8,30 (1H, d, J=1,8 Hz), 8,72 (2H, s), 12,46 (1H, user. C).

(Example 139)

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-3,5-dideoxy-4-O-methyl-1-O-(methanesulfonyl)-L-threo-hexitol

Into a solution of the compound obtained in stage 3 of example 137 (120 mg)in dichloromethane (2.5 ml) was added triethylamine (137 μl) was added dropwise methanesulfonanilide (70 μl) under ice cooling. After stirring at room temperature for 2 hours was added phosphate buffer (pH 7.0), then was diluted with dichloromethane. The organic layer was washed with saturated saline solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain specified in the title compound (179 mg).

Stage 2

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

To a mixed solution of the compound obtained in the above stage 1 (179 mg)in acetonitrile-N,N-dimethylformamide (2:1, 7.5 ml) was added the compound obtained in stage 2 of example 35 (235 mg), and potassium carbonate (221 mg) and the mixture was stirred at 80°C during the night. the donkey dilution with ethyl acetate the organic layer was sequentially washed with water and saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (314 mg).

MS (ESI) m/z: 422 (M+H)+.

Stage 3

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

Specified in the title compound (174 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in the above stage 2 (314 mg).

MS (ESI) m/z: 470 (M+H)+.

Stage 4

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

Specified in the title compound (111 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (174 mg)and the compound obtained in stage 3 of example 36 (94 mg).

MS (ESI) m/z: 474 (M+H)+.

Stage 5

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title compound (47 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained by you is ukazannoi stage 4 (111 mg).

MS (ESI) m/z: 394 (M+H)+.

Stage 6

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol dimethanesulfonate

Specified in the title compound (62 mg) was obtained in a way similar to stage 3 of example 118, using the compound obtained in the above stage 5 (47 mg).

MS (ESI) m/z: 394 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C21H24N5O3394,18791; found: 394,18724.

1H-NMR (DMSO-d6) δ: 1,02-of 1.09 (1H, m), 1,16-1,25 (1H, m), 1,85-1,90 (1H, m), 2,02-to 2.06 (1H, m), 2,32 (6H, s)to 2.54 (3H, s), up 3.22 (3H, s), 3,23 of 3.28 (1H, m), 3,31-3,37 (1H, m), 3,62-3,99 (4H, m), 6.73 x to 6.75 (1H, m), EUR 7.57-EUR 7.57 (1H, m), 7,60 to 7.62 (1H, m), 7,94 (1H, d, J=1.7 Hz), 8,21 (1H, s), of 11.69 (1H, user. C)12,08 (1H, user. C).

(Example 140)

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol

Stage 1

2,6-Anhydrous-3,5-dideoxy-4-O-methyl-1-O-(methanesulfonyl)-D-threo-hexitol

Specified in the title compound (189 mg) was obtained in a way similar to stage 1 of example 139 using the compound obtained in stage 2 of example 138 (128 mg).

Stage 2

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,5-trideoxy-4-O-methyl-D-threo-hexitol

Specified in the title compound (343 mg) was received the way, similar to the one used in stage 2 of example 139 using the compound obtained in the above stage 1 (189 mg)and the compound obtained in stage 2 of example 35 (248 mg).

MS (ESI) m/z: 422 (M+H)+.

Stage 3

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-D-threo-hexitol

Specified in the title compound (215 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in the above stage 2 (341 mg).

MS (ESI) m/z: 470 (M+H)+.

Stage 4

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-D-threo-hexitol

Specified in the title compound (150 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 3 (215 mg)and the compound obtained in stage 3 of example 36 (116 mg).

MS (ESI) m/z: 474 (M+H)+.

Stage 5

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol

Specified in the title compound (76 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 4 (150 mg).

MS (ESI) m/z: 394(M+H) +.

Stage 6

2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-threo-hexitol dimethanesulfonate

Specified in the title compound (106 mg) was obtained in a way similar to stage 3 of example 118, using the compound obtained in the above stage 5 (76 mg).

MS (ESI) m/z: 394 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C21H24N5O3394,18791; found: 394,18758.

1H-NMR (DMSO-D6) δ: 1,02-of 1.09 (1H, m), 1,16-1,25 (1H, m), 1.85 to 1,89 (1H, m), 2,02-to 2.06 (1H, m), of 2.34 (6H, s), to 2.57 (3H, s), 3,23 (3H, s), 3,23 of 3.28 (1H, m), 3,31-3,37 (1H, m), 3,62-3,99 (4H, m), 6,80-PC 6.82 (1H, m), 7,58 (1H, d, J=2.3 Hz), 7,65-7,66 (1H, m), 7,95 (1H, d, J=1.7 Hz), compared to 8.26 (1H, s), 11,72 (1H, user. C), 12,24 (1H, user. C).

(Example 141)

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

and its enantiomer

Stage 1

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

Specified in the title compound (0.34 g) was obtained as colorless solid by the method similar to that applied in stage 4 of example 35 using the compound obtained in stage 3 of example 36 (1 g).

MS (ESI) m/z: 259 (M+H)+.

1H-NMR (CDCl3) δ: to 1.38 (9H, s), 2,78 (3H, s), to 6.57 (1H, d, J=3.6 Hz), 7,28 (1H, d, J=3.2 Hz), 8,66 (1H, s), 10,24 (1H, s).

Stage 2

2,6-Anhydrous-5-Benzoyl-1-[3-cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-DL-threo-hexitol

Specified in the title compound (120 mg) was obtained as a pale yellow oil in a way similar to step 2 of example 4, using the compound obtained in the above stage 1 (113 mg)and the compound obtained in stage 3 of example 112 (150 mg).

MS (ESI) m/z: 564 (M+H)+.

1H-NMR (CDCl3) δ: 1,69-of 1.74 (1H, m), 1,76-of 1.81 (2H, m), 1,84 is 1.91 (3H, m), 2,13-2,19 (1H, m), 2,33-is 2.37 (2H, m), is 2.40 (3H, s), 2,48 is 2.55 (2H, m), the 3.65 (1H, d, J=12,8 Hz), 3,82-a 3.87 (1H, m), a 4.03-4,12 (3H, m), 5,04 (1H, s), 6,09 (1H, s), of 6.52 (1H, d, J=2.2 Hz), 7,31 and 7.36 (3H, m), 7,46-7,52 (2H, m), to 7.84 (2H, d, J=8,2 Hz), of 8.04 (1H, s), 8,11 (1H, s)of 8.92 (1H, user. C).

Stage 3

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

Specified in the title compound (10 mg) was obtained as a pale yellow solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 2 (120 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,38-of 1.41 (1H, m), 1,61-1,71 (3H, m), 2,47 (3H, s), 3,30-to 3.38 (1H, m), 3,52-of 3.54 (1H, m), 3,62-3,66 (2H, m), 3,80-3,93 (2H, m), of 4.54 (1H, d, J=4.0 Hz), 6,56-to 6.57 (1H, m), of 7.48 (1H, t, J=2,8 Hz), 7,54 (1H, d, J=1.7 Hz), of 7.90 (1H, d, J=1.7 Hz), 8,08 (1H, s), of 11.61 (1H, s), 11,65 (1H, s).

(Example 142)

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

and its enantiomer

Stadia

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-DL-threo-hexitol

Specified in the title compound (170 mg) was obtained as a pale yellow oil in a way similar to step 2 of example 4, using the compound obtained in stage 1 of example 141 (138 mg), and the compound obtained in stage 4 of example 113 (150 mg).

MS (ESI) m/z: 474 (M+H)+.

1H-NMR (CDCl3) δ: 1,55-1,65 (4H, m), 1,74 and 1.80 (2H, m), 1,87-of 1.93 (2H, m), of 2.08 and 2.13 (1H, m), 2,32-of 2.36 (2H, m), 2,50 of $ 2.53 (4H, m), 3,21 (1H, s)to 3.33 (3H, d, J=1.3 Hz), 3,42 (1H, d, J=12,8 Hz), 3,71 (1H, t, J=8,9 Hz), of 3.84 (1H, DD, J=14,6, 7,7 Hz), 3,99-4,08 (2H, m), between 6.08-6,10 (1H, m), 6,57-6,59 (1H, m), 7,35 (1H, s)of 7.48 (1H, s), 8,03 (1H, t, J=1,8 Hz), 8,18 (1H, s), 9,14 (1H, s).

Stage 2

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol

Specified in the title compound (53 mg) was obtained as a pale yellow solid in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (170 mg).

MS (ESI) m/z: 394 (M+H)+.

Stage 3

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-DL-threo-hexitol dimethanesulfonate

Specified in the title compound (78 mg) was obtained as a pale yellow solid prophetic the TBA method, similar to the one used in stage 3 of example 118, using the compound obtained in the above stage 2 (53 mg).

MS (ESI) m/z: 394 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,39 was 1.43 (1H, m), 1,48-of 1.62 (2H, m), 1,89-of 1.93 (1H, m), a 2.36-2,41 (9H, m), 2,60-2,62 (2H, m), 3,19 (3H, s), 3,32-to 3.35 (1H, m), 3,66-3,71 (1H, m), 3,79-to 3.92 (3H, m), 6.87 in-6,91 (1H, m), to 7.61 (1H, d, J=4,0 Hz), 7,70-7,73 (1H, m), of 7.96-of 7.97 (1H, m), 8,32-at 8.36 (1H, m), 11,74 (1H, s), 12,41 (1H, s).

(Example 143)

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2-[(Benzyloxy)methyl]-3,4-dihydro-2H-Piran

3,4-Dihydro-2H-Piran-2-ylmethanol (5.0 g) was dissolved in tetrahydrofuran (100 ml). Under ice cooling was added 55% sodium hydride (2.3 g) and benzylbromide (8,2 g), then stirred for 17 hours. Was added a saturated aqueous solution of ammonium chloride, then extracted with ethyl acetate and washed with saturated saline solution. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (8.5 g) as a pale yellow oil.

MS (ESI) m/z: 205 (M+H)+.

1H-NMR (CDCl3) δ: 1,66-of 1.78 (1H, m), 1.85 to of 1.92 (1H, m), 1,96-2,05 (1H, m), 2,07-to 2.18 (1H, m), of 3.56 (1H, DD, J=4,3, 10,3 Hz), 3,63 (1H, DD, J=6,2, 10,3 is C), a 4.03-4,10 (1H, m), br4.61 (1H, d, J=12,4 Hz)and 4.65 (1H, d, J=12,4 Hz), 4,69-4,74 (1H, m), 6.42 per-of 6.45 (1H, m), 7,28-7,40 (m, 5H).

Stage 2

2,6-Anhydrous-1-O-benzyl-3,4-dideoxy-DL-Erythro-hexitol

The compound obtained in the above stage 1 in (8.9 g)was dissolved in tetrahydrofuran (290 ml). Added a 0.5 n solution of 9-borabicyclo[3.3.1]nonane in tetrahydrofuran (122,5 ml) and the mixture was stirred at room temperature for 17 hours. To the reaction solution was added 3 N. aqueous sodium hydroxide solution (43,8 ml), 35% aqueous hydrogen peroxide solution (17 ml) and potassium carbonate (30,2 g), then was stirred for one hour. Next, the reaction solution was diluted with ethyl acetate and washed with saturated saline solution. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (7.2 g) as a pale yellow oil.

1H-NMR (CDCl3) δ: of 1.34 to 1.48 (2H, m)and 1.51-of 1.57 (1H, m)of 1.65 and 1.75 (1H, m)and 3.15 (1H, t, J=10,53 Hz), 3,37-of 3.54 (3H, m), 3,65-of 3.78 (1H, m), to 4.01-4.09 to (1H, m), of 4.54 (1H, d, J=12,4 Hz), 4,60 (1H, d, J=12,4 Hz), 7.24 to 7,37 (5H, m).

Stage 3

2,6-Anhydrous-1-O-benzyl-3,4-dideoxy-5-O-(phenylcarbamoyl)-L-threo-hexitol

2,6-Anhydrous-1-O-benzyl-3,4-dideoxy-5-O-(phenylcarbamoyl)-D-threo-hexitol

Specified in the title compound was obtained as a racemate the way, similar to the one used in stage 1 of example 112, using the compound obtained in the above stage 2 (6.6 g)and benzoic acid (4,32 g).

MS (ESI) m/z: 327 (M+H)+.

1H-NMR (CDCl3) δ: 1,52-to 1.59 (1H, m), 1,76-of 1.92 (2H, m), 2,12-of 2.21 (1H, m), of 3.48 (1H, DD, J=10,1, and 3.7 Hz)and 3.59 (1H, DD, J=10,1, 6.4 Hz), 3,64-of 3.77 (2H, m), is 4.21 (1H, dt, J=13,0, 2.0 Hz), of 4.57 (1H, d, J=12,4 Hz), with 4.64 (1H, d, J=and 12.4 Hz), of 5.05-5,09 (1H, m), 7,27-7,38 (5H, m), 7,40-7,47 (2H, m), 7,53-to 7.59 (1H, m), 8.07-a 8,11 (2H, m).

The resulting racemate was optically analyzed using HPLC with getting listed in the title compounds, L-isomer (isomer A: 4.0 g) and D-isomer (isomer B: 3.7 g), respectively.

Column: CHIRALCEL OD (5 × 50 cm)

Eluent: 25% isopropanol/n-hexane

Flow rate: 25 ml/min

The time of elution: isomer A: 52 min, isomer B: 72 min

The above compound can also be synthesized from known compounds and can be specified by its absolute configuration.

Stage 4

1.5-Anhydrous-3,4-dideoxy-2-O-(phenylcarbamoyl)-L-threo-hexitol

L-isomer obtained in the above stage 3 (isomer A, 3.5 g)was dissolved in methanol (53 ml). Was added 5% palladium on coal (1.1 g) and the mixture was stirred in hydrogen atmosphere at room temperature for 22 hours. The reaction solution was filtered and the filtrate was concentrated under reduced pressure to obtain specified in the title compound (2.3 g) as a colourless oil.

1H-YAM who (CDCl 3) δ: 1,45-of 1.53 (1H, m), 1,78-of 1.94 (2H, m), 2,14-2,22 (1H, m), 3,53 at 3.69 (3H, m), 3,74 (1H, d, J=12,8 Hz), 4,20 (1H, d, J=12,8 Hz), 5,07-5,11 (1H, user. m), was 7.45 (2H, t, J=7.8 Hz), EUR 7.57 (1H, t, J=7.8 Hz), of 8.09 (2H, d, J=7,8 Hz).

Stage 5

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-5-O-(phenylcarbamoyl)-L-threo-hexitol

Specified in the title compound (3.4 g) was obtained in a way similar to stage 3 of example 35 using the compound obtained in the above stage 4 (1.5 g)and the compound obtained in stage 2 of example 35 (2.5 g).

1H-NMR (CDCl3) δ: 1,63-to 1.67 (1H, m), 1,70-1,80 (3H, m), 1,81-of 1.92 (3H, m), 2,12-of 2.20 (1H, m), 2,27-of 2.34 (2H, m), 2,38 at 2.45 (2H, m), the 3.65 (1H, DD, J=13,0, 1.5 Hz), 3,76-a-3.84 (1H, m), of 3.97 (1H, t, J=4.4 Hz), 4.92 in-5,06 (3H, m), 5,98-6,04 (1H, m), 7,42 (2H, t, J=7,7 Hz), 7,53-of 7.60 (2H, m), of 7.90-7,94 (2H, m), 8,08 (1H, d, J=2.0 Hz).

Stage 6

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,4-trideoxy-L-threo-hexitol

The compound obtained in the above stage 5 (3.4 g)was dissolved in methanol (44 ml). Was added potassium carbonate (2.7 g) and the mixture was stirred for 4 hours. The reaction solution was diluted with ethyl acetate, washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the indicated what about the title compound (2.0 g).

MS (ESI) m/z: 408 (M+H)+.

1H-NMR (CDCl3) δ: 1,69-of 1.80 (4H, m), 1,82 is 1.91 (2H, m), 1.93 and of 1.99 (1H, m), 2,01-2,04 (1H, m), and 2.27 to 2.35 (2H, m), 2,39 is 2.46 (2H, m), 3,53 (1H, d, J=12,4 Hz), 3,64-to 3.73 (1H, m), 3,76-3,81 (2H, m), a 3.87-3,93 (1H, m), 3,98 (1H, DD, J=14,7, 2,8 Hz), 5,99-6,04 (1H, m), 7,53 (1H, d, J=1,8 Hz), 8,08 (1H, d, J=1,8 Hz).

Stage 7

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the title compound (1.2 g) was obtained by the method similar to that applied in stage 4 of example 35 using the compound obtained in the above stage 6 (1.1 g).

MS (ESI) m/z: 456 (M+H)+.

1H-NMR (CDCl3) δ: of 1.35 (12H, s), 1,57-of 1.62 (1H, m)of 1.65 and 1.80 (4H, m), 1,81-to 1.98 (3H, m), 2,27-of 2.34 (2H, m), 2,43 is 2.44 (2H, m), 3,53 (1H, DD, J=12,4, 1,4 Hz), 3,70-with 3.79 (2H, m), 3,84-of 3.97 (3H, m), 5,99-6,04 (1H, m), 7,63 (1H, d, J=1.4 Hz), 8,44 (1H, d, J=1.4 Hz).

Stage 8

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the title compound (48 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 7 (150 mg)and the compound obtained in stage 3 of example 36 (83 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1,61-to 1.67 (1H, m), 1.70 to of 1.84 (4H, m), 1,87-of 1.93 (2H, m), 1,94 is 2.00 (1H, m), 2,31-of 2.36 (2H, m), 2,42 (3H, s), 2,49-of 2.54 (2H, user. m)of 3.54 (1H, d, J=12.0 Hz), 3,71-of 3.77 (1H, m), 3,78-3,80 1H, user. m), 3,84-to 3.89 (2H, m), of 4.05 (1H, DD, J=14,6, and 3.2 Hz), 6,07-6,11 (1H, m), 6,51-6,55 (1H, user. m), 7,33-7,37 (2H, m), 8,03 (1H, s), 8,17 (1H, s), 9,96 (1H, user. C).

Stage 9

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title compound (31 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 8 (48 mg).

MS (ESI) m/z: 380 (M+H)+.

HRMS (ESI) [M+H]+calculated: C20H21N5O3380,17226; found: 380,17420.

1H-NMR (DMSO-d6) δ: 1,38 was 1.43 (1H, m), 1.56 to about 1.75 (3H, m), 2,47 (3H, s), 3,48 of 3.56 (1H, m), 3,59-3,61 (2H, m), 3,79-of 3.94 (2H, m), 4,07-of 4.12 (1H, m), 6,55-to 6.57 (1H, m), 7,46-of 7.48 (1H, m), 7,54 (1H, d, J=1.7 Hz), of 7.90 (1H, d, J=1.7 Hz), 8,08 (1H, s), and 11.6 (1H, s)to 11.7 (1H, s).

(Example 144)

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the title compound (57 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 7 of example 143 (150 mg)and the compound obtained in stage 2 of example 124 (89 mg).

MS (ESI) m/z: 474 (M+H)+.

1H-NMR (CDC 3) δ: 1.60-to is 1.81 (5H, m), 1,87-of 1.93 (2H, m), 1,94 of 1.99 (2H, m), 2,31-is 2.37 (2H, m), 2,48-of 2.54 (5H, m), 2,58-2,61 (3H, m), of 3.54 (1H, d, J=12,6 Hz), 3,69-with 3.79 (2H, m), 3,82-are 3.90 (2H, m), Android 4.04 (1H, d, J=14,9 Hz), between 6.08-6,10 (1H, m), 7,05 (1H, s), 7,37 (1H, s), 8,01 (1H, s), of 8.09 (1H, s), 8,81 (1H, user. C).

Stage 2

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title compound (18 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (57 mg).

MS (ESI) m/z: 394 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H23N5O3394,18791; found: 394,18863.

1H-NMR (DMSO-d6) δ: 1,31 of 1.50 (2H, m), 1,55-of 1.81 (3H, m), the 2.46 (3H, s), to 2.57 (3H, s), 3,47-4,06 (5H, m), 7,49 (1H, d, J=1.7 Hz), 7,86 (1H, d, J=1.7 Hz), to 7.99 (1H, s), of 11.61 (1H, s)of 11.26 (1H, s).

(Example 145)

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-(cyclohex-1-EN-1-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the title compound (79 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 7 of example 143 (150 mg)and the compound obtained in stage 2 of example 125 (137 mg).

+.

1H-NMR (CDCl3) δ: 1,62 is 2.01 (8H, m), 2,30-of 2.38 (2H, m), 2,48 is 2.55 (2H, m), 2,68 (3H, s), 3,55 (1H, d, J=and 12.2 Hz), 3,70-3,82 (2H, m), 3,84-to 3.92 (2H, m)4,06 (1H, DD, J=14,6, 2.7 Hz), 6,07-6,11 (1H, m), 7,30 (1H, s), 7,38 (1H, d, J=1.5 Hz), 8,00 (1H, d, J=1.5 Hz), 8,14 (1H, s).

Stage 2

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the title compound (58 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (79 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,36-of 1.44 (1H, m), 1.56 to of 1.80 (3H, m)to 2.66 (3H, s), 3,50 of 3.56 (1H, m), 3,59-3,68 (2H, m), 3,70-to 4.15 (3H, m), 7,53 (1H, d, J=1,8 Hz), 7,66 (1H, d, J=2,8 Hz), 7,89 (1H, d, J=1,8 Hz), 8,13 (1H, s), 11,63 (1H, s)12,00 (1H, s).

(Example 146)

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (790 mg) was obtained in a way similar to stage 1 of example 63, using the compound obtained in stage 6 of example 143 (940 mg).

MS (ESI) m/z: 422 (M+H)+.

1H-NMR (CDCl3) δ: 1,52-1,77 (5H, m), 1,83-1,89 (2H, m), 2,08-of 2.16 (1H, m), 2,27-of 2.34 (2H, m), 2,39 at 2.45 (2H, m), 3,22-of 3.25 (1H, m), 3,37-3,44 (3H,m), to 3.38 (1H, s), 3,63-of 3.78 (2H, m)to 3.99 (1H, DD, J=14,0, 2,5 Hz), of 4.05 (1H, d, J=12,8 Hz), 5,99-of 6.02 (1H, m), 7,60 (1H, d, J=1,8 Hz), of 8.06 (1H, d, J=1,8 Hz).

Stage 2

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (812 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in the above stage 1 (750 mg).

MS (ESI) m/z: 470 (M+H)+.

1H-NMR (CDCl3) δ: of 1.35 (12H, s), 1,48-of 1.65 (2H, m), was 1.69 and 1.80 (3H, m), 1,83-1,90 (2H, m), of 2.08 and 2.13 (1H, m), 2,28-of 2.34 (2H, m), 2,41-2,47 (2H, m), 3,22-of 3.25 (1H, m)to 3.38 (3H, s), of 3.43 (1H, DD, J=12,4, 1,4 Hz), 3,71-of 3.78 (1H, m), 3,85 (1H, DD, J=14,7, and 7.8 Hz), 3,95 (1H, DD, J=14,7, 4.6 Hz), was 4.02-4,08 (1H, m), 5,99-6,03 (1H, m), 7,71 (1H, d, J=1.4 Hz), 8,42 (1H, d, J=1.4 Hz).

Stage 3

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (67 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (155 mg)and the compound obtained in stage 3 of example 36.

MS (ESI) m/z: 474 (M+H)+.

1H-NMR (CDCl3) δ: 1,54 by 1.68 (2H, m), 1,71-of 1.81 (3H, m), 1,87-of 1.94 (2H, m), 2,08-to 2.15 (1H, m), 2,31-of 2.38 (2H, m), 2.49 USD is 2.55 (5H, m), 3,22-3,24 (1H, m)to 3.34 (3H, s), 3,43 (1H, d, J=12,4 Hz), 3,69-of 3.77 (1H, m), 3,88 (1H, DD, J=14,7, and 7.8 Hz), was 4.02 (1H, d, J=12,8 Hz), 4,07 (1H, DD, J=14,7, 2,8 Hz) 6,09 (1H, t, J=3,7 Hz), 6,56-6,59 (1H, m), 7,37 (1H, t, J=2.5 Hz), of 7.48 (2H, d, J=1,8 Hz), of 8.04 (1H, d, J=1,8 Hz), 8,18 (1H, s).

Stage 4

2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title compound (17 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (67 mg).

MS (ESI) m/z: 394 (M+H)+.

HRMS (ESI) [M+H]+calculated: C21H23N5O3394,18791; found: 394,18779.

1H-NMR (DMSO-d6) δ: 1,35-and 1.63 (3H, m), 1,86-of 1.92 (1H, m), of 2.45 (3H, s), or 3.28 (3H, s), 3,62-3,91 (6H, m), 6,54-6,56 (1H, m), 7,46 (1H, t, J=2,9 Hz), 7,51 (1H, d, J=2.3 Hz), 7,88 (1H, d, J=2.3 Hz), of 8.06 (1H, s), 11,59 (1H, user. C)11,63 (1H, user. C).

(Example 147)

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (74 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in stage 2 of example 146 (155 mg)and the compound obtained in stage 2 of example 124 (89 mg).

MS (ESI) m/z: 488 (M+H)+.

1H-NMR (CDCl3) δ: 1,53-1,95 (7, m), 2,08-to 2.15 (1H, m), 2,30-of 2.38 (2H, m), 2.49 USD is 2.55 (5H, m), 2,62 (3H, s), 3,21-3,24 (1H, m)to 3.35 (3H, s), of 3.43 (1H, DD, J=12,6, 1.1 Hz), 3,69-of 3.77 (1H, m), 3,86 (1H, DD, J=14,4, and 7.8 Hz), was 4.02 (2H, d, J=12,4 Hz), 4,06 (2H, DD, J=14,7, and 3.7 Hz), 6,07-6,11 (1H, m), 7,07 (1H, s), 7,46 (1H, d, J=1,8 Hz), 8,01 (1H, d, J=1,8 Hz), of 8.09 (1H, s), 9,37 (1H, s).

Stage 2

2,6-Anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol

Specified in the title compound (21 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (74 mg).

MS (ESI) m/z: 408 (M+H)+.

HRMS (ESI) [M+H]+calculated: C22H25N5O3408,20356; found: 408,20482.

1H-NMR (DMSO-d6) δ: 1.32 to at 1.73 (3H, m), 1,84-to 1.98 (1H, m), the 2.46 (3H, s), 2,58 (3H, s), 3,30 (3H, s), 3,36 is 3.40 (2H, m), 3,62-3,93 (4H, m), 7,20 (1H, s)of 7.48 (1H, d, J=1.7 Hz), 7,86 (1H, d, J=1.7 Hz), to 7.99 (1H, s), 11,27 (1H, s), of 11.61 (1H, s).

(Example 148)

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (103 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained with the adiya's 2 of example 146 (155 mg), and the compound obtained in stage 2 of example 125 (137 mg).

MS (ESI) m/z: 508 (M+H)+.

1H-NMR (CDCl3) δ: 1,54 by 1.68 (2H, m), 1.70 to to 1.82 (3H, m), 1,88-of 1.94 (2H, m), 2,08-2,17 (1H, m), 2,30-of 2.38 (2H, m), 2,49-of 2.56 (2H, m), of 2.72 (3H, s), 3,23-of 3.25 (1H, m)to 3.35 (3H, s), 3,44 (1H, DD, J=12,6, 1.3 Hz), 3,69-of 3.77 (1H, m), 3,88 (1H, DD, J=14,4, 8.1 Hz), was 4.02 (1H, d, J=a 12.7 Hz), 4,08 (1H, DD, J=14,6, 2,9 Hz), 6,09-6,11 (1H, m), 7,32 (1H, s)of 7.48 (2H, d, J=1.9 Hz), 8,00 (1H, d, J=1.9 Hz), 8,15 (1H, s), of 10.58 (1H, s).

Stage 2

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol

Specified in the title compound (57 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (103 mg).

MS (ESI) m/z: 428 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,35-of 1.66 (3H, m), 1,86 is 1.96 (1H, m)to 2.66 (3H, s), 3,30 (3H, s), 3,50-was 4.02 (6H, m), 7,52 (1H, d, J=1,8 Hz), 7,66 (1H, d, J=2,8 Hz), of 7.90 (1H, d, J=1.4 Hz), 8,13 (1H, s), 11,64 (1H, s)12,00 (1H, s).

(Example 149)

2,6-Anhydrous-1,3,4-trideoxy-1-[5-methyl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[6-bromo-3-cyclohex-1-EN-1-yl-5-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-(phenylcarbamoyl)-L-threo-hexitol

Specified in the title compound (1.70 g) was obtained in a way similar to stage 3 of example 35 using the compound, the floor is built in stage 4 of example 143 (0,76 g), and the compound obtained in stage 1 of example 44 (1.29 g).

MS (ESI) m/z: 526 (M+H)+.

Stage 2

2,6-Anhydrous-1-[6-bromo-3-cyclohex-1-EN-1-yl-5-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the header connection (0,627 g) was obtained in a way similar to the stage 6 of example 143, using the compound obtained in the above stage 1 (1.70 g).

MS (ESI) m/z: 422 (M+H)+.

1H-NMR (CDCl3) δ: 1,55-to 1.61 (1H, m), 1,68-to 1.79 (4H, m), 1,82-of 1.88 (2H, m), 1,92 of 1.99 (1H, m), 2,27 is 2.33 (2H, m), 2,42-2,48 (2H, m), 2,59 (3H, s), 3,52 (1H, d, J=12.0 Hz), 3,66-and 3.72 (1H, m), 3,76-3,82 (2H, m)to 3.89 (1H, dt, J=12,0, 2.3 Hz), of 3.94 (1H, DD, J=14,3, 2,9 Hz), 5,99-6,01 (1H, m), 7,51 (1H, s).

Stage 3

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-5-methyl-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-L-threo-hexitol

Specified in the title compound (128 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 2 (139 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (96 mg).

MS (ESI) m/z: 460 (M+H)+.

1H-NMR (CDCl3) δ: 1.56 to and 1.63 (1H, m), 1,65-to 1.82 (4H, m), 1,83-of 1.97 (3H, m), 2,28-of 2.36 (2H, m), 2,48 (3H, s), 2,52-of 2.58 (2H, m), 3,52 (1H, d, J=11,9 Hz), 3,70-with 3.79 (2H, m), 3,85-3,93 (2H, m), of 3.97 (1H, DD, J=14,7, and 3.7 Hz), 6,06-6,10 (1H, m), 6,52-6,55 (1H, m), 7,26 (1H, s), 7,40-the 7.43 (1H, m), 7,87 (1H, d, J=1,8 Hz), compared to 8.26 (1H, d, J=1,8 Hz), 10,43 (1H, s).

Stage 4

2,6-Anhydrous-1,3,4-trideoxy-1-[5-IU the Il-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title compound (20 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 3 (151 mg).

MS (ESI) m/z: 380 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,33-of 1.40 (1H, m), 1,58-of 1.73 (3H, m), of 2.38 (3H, s), 3,35-to 3.38 (1H, m), 3,50-of 3.53 (1H, m), 3,59-to 3.67 (1H, m), of 3.77 (1H, DD, J=14,3, 4.0 Hz), a 3.87 (1H, DD, J=13,7, 7,4 Hz), 4,51 (1H, d, J=4.0 Hz), 6.48 in-6,50 (1H, m), 7,38 (1H, s), 7,52-rate of 7.54 (1H, m), 7,95 (1H, d, J=2.3 Hz), to 8.20 (1H, d, J=2.3 Hz), of 11.45 (1H, s), 11,73 (1H, s).

(Example 150)

2,6-Anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Stage 1

2,6-Anhydrous-4-O-benzoyl-1-O-benzyl-3,5-dideoxy-L-threo-hexitol

Specified in the header connection (2,05 g) was obtained by the method similar to those used in stage 1 of example 111 using the L-isomer obtained in stage 1 of example 137 (isomer A, 1.48 g).

MS (ESI) m/z: 327 (M+H)+.

1H-NMR (CDCl3) δ: 1,54-to 1.63 (1H, m), 1,74-of 1.84 (1H, m), 2,02 and 2.13 (2H, m), 3.46 in-3,62 (3H, m), 3,66-and 3.72 (1H, m), 4,11-4,17 (1H, m), of 4.57 (1H, d, J=12.0 Hz), br4.61 (1H, d, J=12.0 Hz), 5,12-5,20 (1H, m), 7,25-7,33 (2H, m), 7,33-to 7.35 (3H, m), 7,42-7,46 (2H, m), 7,54-7,58 (1H, m), 8,02-with 8.05 (2H, m).

Stage 2

1.5-Anhydrous-3-O-benzoyl-2,4-dideoxy-L-threo-hexitol

Specified in the title compound (1.48 g) was obtained by the method similar to that applied in stage 4 of example 143, using the compound obtained in the above stage 1 (2,05 g).

MS (ESI) m/z: 237 (M+H)+.

1H-NMR (CDCl3) δ: 1,50-of 1.62 (1H, m), 1,73 of-1.83 (1H, m), 1,95 of 1.99 (1H, m), 2,02-2,12 (2H, m), 3,56-and 3.72 (4H, m), 4,10-4,16 (1H, m), 5,14-5,22 (1H, m), 7,42-7,47 (2H, m), 7,54-to 7.59 (1H, m), 8,02-with 8.05 (2H, m).

Stage 3

2,6-Anhydrous-4-O-benzoyl-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,5-trideoxy-L-threo-hexitol

Specified in the title compound (3.15 g) was obtained in a way similar to stage 3 of example 35 using the compound obtained in the above stage 2 (1.48 g)and the compound obtained in stage 2 of example 35 (2,40 g).

MS (ESI) m/z: 512 (M+H)+.

1H-NMR (CDCl3) δ: 1,52-of 1.55 (1H, m), 1.70 to to 1.79 (3H, m), 1,83-1,90 (2H, m), 2,03-of 2.09 (1H, m), 2,22-of 2.27 (1H, m), 2,28 is 2.33 (2H, m), 2,39 at 2.45 (2H, m), 3,50 (1H, TD, J=12,3, 2.3 Hz), 3,78-a-3.84 (1H, m), 3,88 (1H, DD, J=14,3, 6,9 Hz), 4,00 (1H, DD, J=14,3, 3.1 Hz), 4,06-4,11 (1H, m), 5,12-5,20 (1H, m), 6,01-6,04 (1H, m), 7,42-7,47 (2H, m), 7,52 (1H, d, J=2.3 Hz), 7,54-to 7.59 (1H, m), 8,01-of 8.04 (2H, m), of 8.09 (1H, d, J=2.3 Hz).

Stage 4

2,6-Anhydrous-1-(6-bromo-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)-1,3,5-trideoxy-L-threo-hexitol

Specified in the title compound (1.78 g) was obtained in a way similar to the stage 6 of example 143, using the compound obtained in the above stage 3 (3.15 g).

MS (ESI) m/z: 408 (M+H)+.

1H-NMR (CDCl3) δ: 1,24-1,32 (1H, m), 1,46-of 1.62 (2H, m), 1,71-of 1.78 (2H, m), 1,83-of 1.92 (3H, m), 2,03-of 2.09 (1H, m), 2,28-of 2.34 (2H, m), 2,39 at 2.45 (2H, m)to 3.35 (1H, TD, J=12,0, 2.3 Hz), 3,63 at 3.69 (1H, m), 3,78-3,86 (2H, m), 3.96 points-a 4.03 (2H, m), 5,99-6,3 (1H, m)to 7.50 (1H, d, J=1.7 Hz), 8,08 (1H, d, J=1.7 Hz).

Stage 5

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-L-threo-hexitol

Specified in the title compound (768 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in the above stage 4 (800 mg).

MS (ESI) m/z: 456 (M+H)+.

1H-NMR (CDCl3) δ: 1,23-of 1.29 (1H, m)of 1.35 (12H, s), 1,47-of 1.64 (2H, m), 1,72-to 1.79 (2H, m), 1,84-1,90 (3H, m), 2,01-2,07 (1H, m), 2,28-of 2.34 (2H, m), 2,41-2,47 (2H, m)to 3.35 (1H, DD, J=12,7, 1.7 Hz), 3,69-was 4.02 (5H, m), 6,00-6,03 (1H, m), a 7.62 (1H, d, J=1.7 Hz), 8,44 (1H, d, J=1.7 Hz).

Stage 6

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-L-threo-hexitol

Specified in the title compound (127 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in the above stage 5 (147 mg)and the compound obtained in stage 2 of example 124 (66 mg).

MS (ESI) m/z: 474 (M+H)+.

1H-NMR (CDCl3) δ: 1,20-2,12 (8H, m), 2.26 and is 2.55 (4H, m), 2,52 (3H, s)of 2.64 (3H, s), 3,31 is 3.40 (1H, m), 3,64-4,08 (5H, m), 6,07-6,11 (1H, m), 7,06 (1H, s), 7,39 (1H, d, J=1.7 Hz), 8,03 (1H, d, J=1.7 Hz), 8,11 (1H, s), to 8.62 (1H, user. C).

Stage 7

2,6-Anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol

Specified in the title is information connection (44 mg) was obtained by way similar to the stage 6 of example 35 using the compound obtained in the above stage 6 (125 mg).

MS (ESI) m/z: 394 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,03-of 1.13 (1H, m), 1,19-of 1.30 (1H, m), 1,65-1,72 (1H, m), 1,79-to 1.87 (1H, m), the 2.46 (3H, s), to 2.57 (3H, s), 3,21 of 3.28 (1H, m), 3,52-the 3.65 (2H, m), 3,76-3,86 (2H, m)to 3.92 (1H, DD, J=14,3, 7,4 Hz), of 4.77 (1H, d, J=5,2 Hz), 7,19-7,21 (1H, m), of 7.48 (1H, d, J=1.7 Hz), 7,87 (1H, d, J=1.7 Hz), to 7.99 (1H, s), 11,27 (1H, s), are 11.62 (1H, s).

(Example 151)

2,6-Anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-[3-cyclohex-1-EN-1-yl-6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

Specified in the title compound (113 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in stage 3 of example 139 (165 mg)and the compound obtained in stage 2 of example 124 (66 mg).

MS (ESI) m/z: 488 (M+H)+.

1H-NMR (CDCl3) δ: 1.10 is a 1.96 (8H, m), 2,32-of 2.38 (2H, m), 2,50-of 2.54 (2H, m), 2,52 (3H, s)of 2.64 (3H, s), 3,29 is 3.40 (2H, m)to 3.36 (3H, s), 3,65-and 3.72 (1H, m), 3,84-4,07 (3H, m), 6,07-to 6.22 (1H, m), 7,05 (1H, s), 7,39 (1H, d, J=1.7 Hz), 8,02 (1H, d, J=1.7 Hz), 8,10 (1H, s)of 8.37 (1H, user. C).

Stage 2

2,6-Anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol

Pointed to by the e in the title compound (28 mg) was obtained by way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (110 mg).

MS (ESI) m/z: 408 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,00-1,11 (1H, m), 1,15-of 1.26 (1H, m), 1,83-1,90 (1H, m), 2,01-2,07 (1H, m), the 2.46 (3H, s), to 2.57 (3H, s), 3,23 (3H, s), 3,24 is 3.40 (2H, m), 3,60-3,68 (1H, m), 3,81-3,98 (3H, m), 7,19-7,21 (1H, m), of 7.48 (1H, d, J=1.7 Hz), 7,87 (1H, d, J=1.7 Hz), to 7.99 (1H, s), 11,27 (1H, s), of 11.61 (1H, s).

(Example 152)

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

Stage 1

2,6-Anhydrous-1-{6-[1-(tert-butoxycarbonyl)-3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl]-3-cyclohex-1-EN-1-yl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl}-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

Specified in the title compound (119 mg) was obtained in a way similar to step 2 of example 4, using the compound obtained in stage 3 of example 139 (163 mg)and the compound obtained in stage 2 of example 125 (100 mg).

1H-NMR (CDCl3) δ: 1,16-of 1.26 (1H, m)of 1.24 (9H, s), of 1.35 to 1.47 (1H, m), 1,73-of 1.81 (2H, m), 1,87 is 1.96 (3H, m), 2,13-2,19 (1H, m), 2,32-is 2.37 (2H, m), 2,48-of 2.54 (2H, m), is 2.74 (3H, s), 3,30 is 3.40 (2H, m)to 3.36 (3H, s), 3,65-3,71 (1H, m), a 3.87 (1H, DD, J=14,9, 8.0 Hz), 3.95 to 3,99 (1H, m), of 4.05 (1H, DD, J=14,9, 2,9 Hz), between 6.08-6,11 (1H, m), 7,28-7,30 (1H, m), 7,40 (1H, d, J=1.7 Hz), 8,01 (1H, d, J=1.7 Hz), 8,18 (1H, s).

Stage 2

2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-the l]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol

Specified in the title compound (28 mg) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 1 (116 mg).

MS (ESI) m/z: 428 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,02-1,10 (1H, m), 1,15-of 1.26 (1H, m), 1,84-1,89 (1H, m), 2,01-2,07 (1H, m)to 2.66 (3H, s), 3,23 (3H, s), 3,24-to 3.38 (2H, m), 3,62-3,68 (1H, m), 3,81-a 3.87 (2H, m), of 3.94 (1H, DD, J=14,5, 7,8 Hz), 7,51-7,53 (1H, m), 7,66 (1H, d, J=2,9 Hz), of 7.90 (1H, d, J=2.3 Hz), to 8.12 (1H, s), 11,65 (1H, s), 11,98-12,02 (1H, m).

(Example 153)

1-{[(2S)-6-(Methoxymethyl)-1,4-dioxane-2-yl]methyl}-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

(2R)-1-(Allyloxy)-3-chloropropane-2-ol

To allyl alcohol (11 ml) was added to the complex of boron TRIFLUORIDE-diethyl ether (0,34 ml) and the mixture was heated to 45°C. Then was added (R)-epichlorohydrin (5.0 g) and the mixture was stirred at the same temperature for 1.5 hours. Added diethyl ether, then washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to get crude specified in the title compound (10 g).

1H-NMR (CDCl3) δ: 3,54 at 3.69 (4H, m), 3,97-of 4.05 (2H, m), 4,16-4,18 (1H, m), 5,15-5,24 (1H, m), 5,27-5,31 (1H, m), 5,85-6,05 (1H, m).

Stage 2

(2R)-1-(Allyloxy)-3-(benzyloxy)propan-2-ol

In water (6.4 ml) was dissolved sodium hydroxide (5.4 g). Added the compound obtained in the above stage 1 (8,1 is), and the mixture was stirred at room temperature for 1.5 hours. Added diethyl ether, then washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in benzyl alcohol (27 ml) and was slowly added sodium hydride (55%, 1.8 g) under cooling with ice. The mixture was stirred at room temperature for 4.5 hours and the reaction solution was diluted with dichloromethane. Then the organic layer is successively washed with 1 M hydrochloric acid and saturated aqueous sodium bicarbonate. After drying over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (2.6 g).

1H-NMR (CDCl3) δ: 2,48 (1H, d, J=4.0 Hz), 3,47-to 3.58 (4H, m), 3,98-a 4.03 (3H, m), 4,56 (2H, s), 5,17-5,20 (1H, m), 5.25-in of 5.29 (1H, m), 5,86-5,94 (1H, m), 7,30-to 7.35 (5H, m).

Stage 3

(2S)-2-[(Benzyloxy)methyl]-6-(iodomethyl)1,4-dioxane

Into a solution of the compound obtained in the above stage 2 (2.6 g)in acetonitrile (40 ml) was added N-jodatime (4.5 g) and the mixture was heated under reflux for 2.5 hours. After cooling to room temperature was added a saturated aqueous solution of sodium thiosulfate, then extra Aravali with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.7 g).

1H-NMR (CDCl3) δ: 3.04 from-4,28 (10H, m), 4,54-4,59 (2H, m), 7,27-7,37 (5H, m).

Stage 4

{(6S)-6-[(Benzyloxy)methyl]-1,4-dioxane-2-yl}methyl 4-nitrobenzoate

Into a solution of the compound obtained in the above stage 3 (1.7 g)in dimethylsulfoxide (60 ml) was added 4-nitrobenzoate potassium (10 g) and 18-crown-6-ether (0,13 g) and the mixture was stirred at 90°C for 4 hours. The reaction solution was left to cool to room temperature and was diluted with water and diethyl ether. The organic layer was sequentially washed with water and saturated salt solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (1.7 g).

1H-NMR (CD3OD) δ: 3,35-4,79 (12H, m), 7.24 to 7,34 (5H, m), 8,21-8,35 (5H, m).

Stage 5

{(6S)-6-[(Benzyloxy)methyl]-1,4-dioxane-2-yl}methanol

Into a solution of the compound obtained in the above stage 4 (1.7 g)in methanol (40 ml) was added concentrated hydrochloric acid (1.0 ml). A mixture of AC is stirred at room temperature for 24 hours and was stirred at 50°C for 8 hours. Addition was added concentrated hydrochloric acid (2.0 ml) and the mixture was stirred at the same temperature for 16 hours. Was added concentrated hydrochloric acid (2.0 ml) and the mixture was stirred at the same temperature for 8 hours. The reaction solution was neutralized with a saturated aqueous solution of sodium bicarbonate and methanol drove away under reduced pressure. Added water, then was extracted with diethyl ether. Next, the organic layer was washed with saturated saline solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (258 mg).

1H-NMR (CDCl3) δ: 1.93 and is 2.01 (1H, m), 3,31-4,03 (10H, m), 4.53-in-4,60 (2H, m), 7,29-7,37 (5H, m).

Stage 6

(2S)-2-[(Benzyloxy)methyl]-6-methoxymethyl-1,4-dioxane

Specified in the title compound (261 mg) was obtained in a way similar to stage 1 of example 63, using the compound obtained in the above stage 5 (258 mg).

MS (ESI) m/z: 253 (M+H)+.

Stage 7

[(2S)-6-(Methoxymethyl)-1,4-dioxane-2-yl]methanol

Specified in the title compound (160 mg) was obtained in a way similar to stage 4 of example 114, using the compound obtained in the above is Anna stage 6 (261 mg).

Stage 8

[(2S)-6-(Methoxymethyl)-1,4-dioxane-2-yl]methyl methanesulfonate

Specified in the title compound (235 mg) was obtained in a way similar to stage 1 of example 139 using the compound obtained in the above stage 7 (160 mg).

Stage 9

6-Bromo-3-cyclohex-1-EN-1-yl-1-{[(2S)-6-(methoxymethyl)-1,4-dioxane-2-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (440 mg) was obtained in a way similar to step 2 of example 139 using the compound obtained in the above stage 8 (235 mg)and the compound obtained in stage 2 of example 35 (288 mg).

MS (ESI) m/z: 438 (M+H)+.

Stage 10

3-Cyclohex-1-EN-1-yl-1-{[(2S)-6-(methoxymethyl)-1,4-dioxane-2-yl]methyl}-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (611 mg) was obtained in a way similar to stage 4 of example 35 using the compound obtained in the above stage 9 (440 mg).

MS (ESI) m/z: 486 (M+H)+.

Stage 11

3-Cyclohex-1-EN-1-yl-1-{[(2S)-6-(methoxymethyl)-1,4-dioxane-2-yl]methyl}-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (370 mg) was obtained in a way similar to stage 3 of example 1 using the compound obtained in the above stage 10 (611 mg), and connect the s, obtained in stage 3 of example 36 (292 mg).

MS (ESI) m/z: 490 (M+H)+.

Stage 12

1-{[(2S)-6-(Methoxymethyl)-1,4-dioxane-2-yl]methyl}-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (85 mg) (representing, as it was defined, the mixture ratio of diastereomers, equal to about 3:2 in accordance with NMR) was obtained in a way similar to the stage 6 of example 35 using the compound obtained in the above stage 11 (370 mg).

MS (ESI) m/z: 410 (M+H)+.

HRMS (ESI) [(M+H)+] calculated: C21H24N5O4410,18283; found: 410,18340.

1H-NMR (DMSO-d6) δ: 2,46-2,47 (3H, m), 3,06 (1,8H, s), 3,14 (1,2H, C), 3,15-4,40 (10H, m), 6,56 return of 6.58 (1H, m), 7,47-of 7.48 (1H, m), 7,54-7,55 (0,6H, m), 7,60-7,62 (0,4H, m), to $ 7.91-a 7.92 (1H, m), 8.07-a 8,08 (1H, m), 11,64-11,65 (2H, m).

(Example 154)

2,6-Anhydrous-1,3,5-trideoxy-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-Erythro-hexitol

Stage 1

2,6-Anhydrous-1-O-benzyl-3,5-dideoxy-4-O-(phenylcarbamoyl)-D-Erythro-hexitol

Specified in the header connection (1175 mg) was obtained in a way similar to stage 1 of example 112, using the L-isomer obtained in stage 1 of example 137 (isomer A, 800 mg)and benzoic acid (571 mg).

MS (ESI) m/z: 327 (M+H)+.

1H-NMR (CDCl3) δ: 1,75-to 1.82 (1H, m), 1.85 to of 1.92 (2H, m), 1,96-2,04 (1H, m), 3.45 points-of 3.53 (2H, m), 392-4,08 (3H, m), 4,58 (1H, d, J=12,4 Hz), to 4.62 (1H, d, J=12,4 Hz), 5,46-of 5.50 (1H, m), 7,27-to 7.32 (1H, m), 7,33-7,40 (4H, m), 7,44 is 7.50 (2H, m), EUR 7.57 to 7.62 (1H, m), 8,08 (2H, d, J=7,8 Hz).

Stage 2

2,6-Anhydrous-3,5-dideoxy-4-O-(phenylcarbamoyl)-D-Erythro-hexitol

Specified in the title compound (71 mg) was obtained in a way similar to stage 4 of example 114, using the compound obtained in stage 1 (120 mg), 20% palladium hydroxide (20 mg) and methanol as a solvent.

MS (ESI) m/z: 237 (M+H)+.

Stage 3

Ethyl 6-bromo-3-(2-cyanoethyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate

Specified in the header connection (954 mg) was obtained in a way similar to stage 3 of example 35 using 6-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate, obtained in the conditions described in WO 2008/051493 (1,43 g)and 3-hydroxypropionitrile (0.51 ml).

MS (APCI) m/z: 339 [M+H]+.

1H-NMR (CDCl3) δ: for 1.49 (3H, t, J=7.2 Hz), to 2.94 (2H, t, J=7.0 Hz), 4,28 (2H, t, J=7.0 Hz), 4,55 (2H, q, J=7.2 Hz), 8,23 (2H, s).

Stage 4

3-(6-Bromo-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)propanenitrile

The compound obtained in the above stage 3 (954 mg), was dissolved in tetrahydrofuran (28 ml). Added Isopropylamine (362 μl) and the mixture was stirred at room temperature for 70 minutes. After removal of the solvent the reaction mixture was added hexane and treated with ultrasound. A colorless crystalline substance is collected by filtration to obtain specified in the connection header (739 mg).

MS (APCI) m/z: 267 [M+H]+.

1H-NMR (DMSO-d6) δ: a 3.01 (2H, t, J=6.4 Hz), 4,07 (2H, t, J=6.4 Hz), 7,54 (1H, t, J=1.6 Hz), 8,07 (1H, t, J=1,8 Hz).

Stage 5

2,6-Anhydrous-1-[6-bromo-3-(2-cyanoethyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-(phenylcarbamoyl)-D-Erythro-hexitol

Specified in the title compound (96 mg) was obtained in a way similar to stage 3 of example 35 using the compound obtained in the above stage 2 (71 mg)and the compound obtained in the above stage 4 (104 mg).

MS (ESI) m/z: 485 (M+H)+.

1H-NMR (CDCl3) δ: 1,67-1,72 (1H, m), 1,82-of 1.88 (1H, m), 1,90-of 1.97 (1H, m), 2,02-2,07 (1H, m), 2,95 (2H, t, J=6.3 Hz), of 3.77-of 3.85 (2H, m), 3,88-3,93 (1H, m)4,00 (1H, DD, J=14,3, 2,9 Hz), 4,08-to 4.14 (1H, m), the 4.29 (2H, t, J=6,9 Hz), the 5.45 of 5.48 (1H, m), 7,46 (2H, t, J=7.4 Hz), 7,56-of 7.60 (2H, m), 8,05-with 8.05 (2H, m), of 8.09 (1H, d, J=2.3 Hz).

Stage 6

2,6-Anhydrous-1-[3-(2-cyanoethyl)-2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-D-Erythro-hexitol

Specified in the title compound (20 mg) was obtained in a way similar to stage 4 of example 111 using the compound obtained in the above stage 5 (86 mg)and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (52 mg).

MS (ESI) m/z: 419 (M+H)+.

1H-NMR (CDCl3) δ: 1,52-to 1.67 (2H, m), 1,76-to 1.87 (2H, m), a 3.01 (2H, t, J=6.8 Hz), to 3.73-with 3.79 (1H, m), a-3.84 (1H, DD, J=12,9 and 2.2 Hz), a 3.87-of 3.96 (1H, m)to 4.01 (1H, DD, J=14,6, 3,4 Hz), 4,15-is 4.21 (1H, m), 4,28-or 4.31 (1H, m), 4,37 (2H,, t, J=7,1 Hz, 6,58-6,60 (1H, m), 7,42 (1H, DD, J=3,4 and 2.2 Hz), to 7.64 (1H, d, J=2.0 Hz), of 8.09 (1H, d, J=1.7 Hz), compared to 8.26 (1H, d, J=2.0 Hz), 8,49 (1H, d, J=2.2 Hz), for 9.90 (1H, s).

Stage 7

2,6-Anhydrous-1,3,5-trideoxy-1-[2-oxo-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-D-Erythro-hexitol

The compound obtained in the above stage 6 (20 mg), was dissolved in tetrahydrofuran (1 ml). Added tert-piperonyl potassium (5.3 mg), then stirred. Added tert-piperonyl potassium (11 mg) and acetonitrile (4 ml) and then was further added tert-piperonyl potassium (33 mg). The mixture was stirred at room temperature for three days. Was added a saturated aqueous solution of ammonium chloride, then extracted with ethyl acetate three times. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. To the residue was added hexane and the precipitate was collected by filtration to obtain specified in the title compound (3 mg).

MS (ESI) m/z: 366 (M+H)+.

1H-NMR (DMSO-d6) δ: 1,36 was 1.69 (4H, m), to 3.58-3,71 (1H, m), 3,79-of 3.95 (2H, m), 4,00-4,08 (2H, m), 4,62 with 4.65 (1H, m), 6,51-6,53 (1H, m), 7,52-rate of 7.54 (1H, m), 7,78 (1H, d, J=1.7 Hz), 8,21-8,24 (2H, m), 8,51 (1H, d, J=2.0 Hz), 11,60 (1H, s), 11,73 (1H, s).

(Example 155)

5-Chloro-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Stage 1

6-Bromo-5-chloro-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

5-D is-6-chloropyridine-2,3-diamine, obtained by the method described in Bioorg. Med. Chem. Lett. 1996, 22, 2749 (0,83 g), was dissolved in tetrahydrofuran (40 ml). Added 1,1-carbonyldiimidazole (0,91 g) and the mixture was heated under reflux overnight. The solvent of the reaction mixture is kept under reduced pressure. The obtained residue was washed with hexane/ethyl acetate and then dried under reduced pressure to obtain specified in the connection header (0,81 g).

MS (ESI) m/z: 248 (M+H)+.

1H-NMR (DMSO-d6) δ: 7,58 (1H, s), 11,18 (1H, s), 11,74 (1H, s).

Stage 2

Ethyl 6-bromo-5-chloro-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate

The compound obtained in the above stage 1 (300 mg), was dissolved in dimethylformamide (5 ml). Was added ethyl pyridine-2-yl carbonate obtained by the method described in WO 2008/051493 (242 mg), and potassium carbonate (200 mg) and the mixture was stirred at 55°C for one hour. After cooling the reaction solution to room temperature, added water (6 ml) and 1 N. aqueous solution of hydrochloric acid (2.9 ml) and the mixture was intensively stirred. The precipitated solid was collected by filtration, washed with water and then dried under reduced pressure to obtain specified in the title compound (344 mg).

MS (ESI) m/z: 322 (M+H)+.

1H-NMR (DMSO-d6) δ: of 1.35 (3H, t, J=7,1 Hz), 4,42 (2H, q, J=7.2 Hz), 8,08 (1H, s), KZT 12.39 (1H, s).

Stage 3

6-Bromo-5-chloro-3-[2-(trimethy silyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above stage 2 (340 mg)was dissolved in tetrahydrofuran (10 ml). Was added 2-(trimethylsilyl)ethanol (228 μl) and triphenylphosphine (417 mg) and then was added dropwise diisopropylethylamine (324 μl) under ice cooling. The mixture was stirred overnight while gradually warming to room temperature. After this addition was added 2-(trimethylsilyl)ethanol (228 μl) and triphenylphosphine (417 g) and then was added dropwise diisopropylethylamine (324 μl) under ice cooling. The mixture was stirred for 6 hours while gradually warming to room temperature. The reaction solution was again cooled in an ice bath and then added Isopropylamine (136 μl). The mixture was stirred at room temperature for one hour. The solvent of the reaction mixture is kept under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane) to obtain the specified title compound (310 mg).

1H-NMR (CDCl3) δ: 0,09 (9H, s), 1,12-of 1.16 (2H, m), 3,97-4,01 (2H, m), 7,52 (1H, s), 9,16 (1H, s).

Stage 4

6-Bromo-5-chloro-1-[(2S)-1,4-dioxane-2-ylmethyl]-3-[2-(trimethylsilyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (175 mg) was obtained in a way similar to stage 3 of example 35 using is connected to the e, obtained in the above stage 3 (150 mg)and (2S)-1,4-dioxane-2-ylmethanol (65 mg).

MS (ESI) m/z: 448 (M+H)+.

1H-NMR (CDCl3) δ: 0,07 (9H, s), 3,31-to 3.35 (1H, m), 3,52-to 3.58 (1H, m), 3,64-3,70 (2H, m), 3,76-3,81 (2H, m), 3,84-3,91 (3H, m), 3,98-4,01 (2H, m), 4,96 is 5.07 (2H, m), 7,56 (1H, s).

Stage 5

5-Chloro-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-3-[2-(trimethylsilyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

Specified in the title compound (160 mg) was obtained in a way similar to step 2 of example 4, using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (110 mg) and the compound obtained in the above stage 4 (170 mg).

MS (ESI) m/z: 486 (M+H)+.

1H-NMR (CDCl3) δ: 0,10 (9H, s), 1,18 of 1.28 (3H, m), 3.33 and-to 3.38 (1H, m), 3,50 is 3.57 (1H, m), 3,65-3,74 (3H, m), 3,84-of 3.95 (3H, m), 4,05-4,10 (2H, m), 6,58-6,59 (1H, m), 7,38 (2H, DD, J=6,4, and 3.7 Hz), 8,03 (1H, d, J=1,8 Hz), at 8.36 (1H, d, J=2.3 Hz), 8,87 (1H, s).

Stage 6

5-Chloro-1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-he

The compound obtained in the above stage 5 (130 mg)was dissolved in tetrahydrofuran (5 ml). Added tetrabutylammonium fluoride (a 1.0 M solution in tetrahydrofuran) (1 ml) and the mixture was stirred at 80ºC for three days. The solvent of the reaction mixture is kept under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel (elwira a mixture of ethyl acetate-hexane). Then p is obtained residue was washed with ethyl acetate and then dried under reduced pressure to obtain specified in the title compound (50 mg) in the form of a solid of light yellow color.

HRMS (ESI) [M+H]+calculated: C18H17ClN5O3386,10199; found: 386,10351.

MS (ESI) m/z: 386 (M+H)+.

1H-NMR (DMSO-d6) δ: 3.27 to and 3.31 (1H, m), 3,40-of 3.53 (2H, m), 3,57-3,61 (1H, m), 3,68-and 3.72 (1H, m), 3.75 to the 3.89 (3H, m), 3,91-of 3.96 (1H, m), of 6.52 (1H, DD, J=3,7, 1.8 Hz), 7,54-7,56 (1H, m), to 7.67 (1H, s), of 8.04 (1H, d, J=1,8 Hz), 8,27 (1H, d, J=2.3 Hz), to 11.79 (1H, user. C)11,89 (1H, user. C).

(An example of obtaining a pharmaceutical preparation 1) Hard capsules

To obtain capsules for a single injection every standard capsule consisting of two solid gelatinous parts, fill 100 mg given as an example powdered compounds 1, 150 mg of lactose, 50 mg of cellulose and 6 mg of magnesium stearate. The capsule is washed and then dried.

(An example of obtaining a pharmaceutical product 2) Soft capsules

Get the mixture is given as example compound 1 in oil, digestive, such as soybean oil, cottonseed oil or olive oil, and Inuktitut in a gelatin capsule using a piston pump to obtain soft capsules containing 100 mg of active ingredient. The capsule is washed and then dried.

(An example of obtaining a pharmaceutical preparation 3) Tablets

Tablets receive the usual way, using 100 mg given as example compound 1, 0.2 mg of colloidal silicone dioxide, 5 mg of magnesium stearate, 275 mg microcrystallites the second cellulose, 11 mg of starch and 98,8 mg of lactose. If necessary, the tablet is covered with a shell.

(Test example 1) Investigation of inhibiting the activity of mTOR kinase

The activity of mTOR kinase was measured in the presence or absence of the tested compound. Substrate peptide fosfauriliruetsa under the action of mTOR kinase. Complex streptavidin-XL665 and antibody against phosphorylated S6K (Thr389)/antimachine IgG-cryptit associated with this phosphorylated peptide. At this point, the power transmission resonance fluorescence derived from the antibody/antimachine IgG-cryptate subjected to light irradiation XL665, resulting in the emission of fluorescence at a wavelength of 665 nm. Using this principle register the activity of mTOR kinase. In the presence of an inhibitor of mTOR phosphorylation substrate peptide inhibited and the above complex is not associated with substrate peptide. The result is not resonance energy transfer fluorescence, and fluorescence at a wavelength of 665 nm weakens.

(1) Obtaining samples and the enzymatic reaction

Received cell line HEK293, which constituitive expresses His-tag fused with mTOR person. His-tag was introduced at the N-end of the part corresponding 1362-2549 amino acids at the C-end of mTOR person. Cell lysate was obtained from this HEK293 cell line constitutively expressing His-IU the military mTOR (1362C), and His-tagged mTOR (1362C) was purified in the usual way, using the affinity His-tag.

Then received mTOR enzyme solution which contains the above-mentioned enzyme His-tagged mTOR (1362C), 8 µg/ml biotinylated peptide (Biotin-Ahx-KKANQVFLGFTYVAPSVLESVKE-amide (Sigma)and 50 mm HEPES (pH 7.5), 20 mm MnCl21 mg/ml BSA, a suitable number of cocktail that inhibits protease (full-free EDTA, Roche), 100 ng/ml calyculin A, 4 μg/ml cantharidin and 10 mm DTT as other components.

The investigated compound was dissolved in DMSO and serially diluted to 20 μm ATP solution (50 mm HEPES (pH 7.5), 20 μm ATP) to achieve concentrations required for the study. Into each well of 384-well white tablet Greiner small amount was applied 5 µl of the connection.

In the above-mentioned hole containing the investigated compound were added 5 μl of mTOR enzyme solution. After mixing for carrying out the enzymatic reaction mixture incubated at room temperature for 3 hours.

Similar actions are performed with a solution of DMSO in 20 μm ATP solution as positive control and DMSO solution in 50 mm HEPES (pH 7.5) as a negative control.

(2) Detection of the enzymatic reaction

After carrying out the enzymatic reaction was added to 5 µl of each solution of europium (solution antimachine IgG-cryptit (SCETI Medical Labo .K) and antibody against phosphorylated S6K (Thr389) (Cell Signaling Technology Inc.) in 50 mm HEPES (pH 7.5), 100 mm EDTA and 1.5 mg/ml BSA) and XL665 solution (a solution of streptavidin-XL665 (SCETI Medical Labo K.K.) in 50 mm HEPES (pH 7.5), 100 mm EDTA, 0.8 M KF and 1.5 mg/ml BSA) in that order and then stirred. The mixture is incubated at 4°C over night. The next day the mixture was heated to room temperature and subjected to light irradiation with a wavelength of 337 nm. Fluorescence at a wavelength of 620 nm and fluorescence at a wavelength of 665 nm was measured using a RUBYstar (BMG).

Using the ratio calculated from the measured values was determined by the inhibition of mTOR activity (%) as an index of enzyme activity. In this case, the ratio was calculated using the following formula (1).

Ratio = 10000 × the value of the fluorescence at 665 nm/value of fluorescence at 620 nm ... (1)

Activity inhibition of the enzyme mTOR (%) was determined by the following formula (2).

Activity inhibition of the enzyme mTOR (%) = 100×[(P-S)/(P-N)] ... (2)

P: the Ratio in well with the positive control

N: the Ratio of the hole with a negative control

S: the Ratio of the hole containing the analyzed connection

Next, the optimal curve was determined on the basis of each concentration of tested compound obtained in serial dilutions, and inhibition of enzyme activity of mTOR (%) at this concentration. The concentration at which 50% inhibition, the treatment tip can itively as IC 50the values of inhibition of enzyme activity of mTOR.

Compounds with the value of the IC50less than 0.05 μm were compounds of examples 1, 3-7, 9, 10, 15-29, 31-55, 58-72, 76, 78, 79, 81-84, 90, 92, 93, 95-130, 133-153 and 155. Compounds with the value of the IC50equal to 0.05 μm or higher and lower than 0.1 μm, were compounds of examples 57, 75 and 77. Compounds with the value of the IC500.1 μm or above and less than 5 μm, were compounds of examples 2, 8, 11-14, 30, 56, 73, 74, 80, 85-89, 91, 94, 131, and 132.

(Test example 2) investigation of the inhibition of cell proliferation

Cells WM-266-4 (ATCC, USA) were sown in 96-well plate and grown over night. Then got a serial dilution of the sample containing the analyzed compound was added to each well and grown for another three days. Then measured the number of cells in each well using MTT (MOSMANN, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65, 55 to 63 (1983)). 50% inhibition activity of cell proliferation (GI50value) was calculated using the following formula (3).

100×[(T-T0)/(C-T0)]=50 ... (3)

In this formula, T represents the value of the wells with the addition of the compounds, C represents the value of the wells, which did not add an investigational compound for three days, and T0represents the initial measured value at tramadolonline the compounds.

Compounds that demonstrated the value GI50less than 3 μm, were compounds of example 1-7, 9, 15-21, 23-29, 31-55, 58, 60-65, 67-71, 75, 78, 79, 81-83, 88, 90-92, 96, 98-105, 107, 108, 111-129, 133-153 and 155. Compounds that demonstrated the value GI50equal to 3 μm or above and less than 25 μm, were connection example 8, 10, 14, 56, 57, 59, 72-74, 76, 77, 84-87, 89, 93-95, 97, 109, 110 and 130-132.

(Test example 3) anti-tumor effect in vivo

Suspension with a volume of 0.1 ml of tumor cells, brought to a concentration of 3-10×107cells per ml, or a solid tumor, chopped 3-5 mm size3subcutaneously transplanted BALB/c Nude" mice (age 6-8 weeks) and mice were kept up until the tumor volume reached volume greater than 100 mm3. Depending on the tumor volume of the mice were divided into groups. The investigated compound was dissolved or suspended in a suitable solvent and injected into mice orally or intraperitoneally. Time ranged from two to four weeks, depending on the type of tumor. Length (mm) width (mm) of the tumor were measured with digital calipers and tumor volume is measured was calculated using the formula (4)below. Calculated degree of inhibition of tumor growth on a particular day (TGI%). Measured body weight and observed the General condition in the implementation process. The investigated compound was evaluated as now is the case, if tumor growth inhibited without the death of the animal, a significant reduction in body weight or pathological manifestations.

TGI (%) = (1-A/B)×100 ... (4)

A: the average tumor volume in the group of animals that were administered connection (*) on a particular day.

B: the mean tumor volume in the control animals, which did not enter connection (*) on a particular day.

*: Tumor volume was calculated using the formula: 1/2 × [length tumors] × [width tumor] × [width tumors].

Industrial applicability

The compound of the present invention has a strong activity of inhibiting mTOR and excellent antitumor activity and respectively used as medicines, particularly anti-cancer agents.

1. The connection represented by the General formula (I):

where in the General formula (I)
(R1)n-A represents a 1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-fluoro-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-ilen group or 3-chloro-4-methyl-1H-feast of the olo[2,3-b]pyridine-5-ilen group,
Represents a 3-6-membered saturated or partially saturated monocyclic hydrocarbon group and may contain 1 or 2 oxygen atom, nitrogen atom, and/or sulfonylurea groups as constituents of the ring
In may as the substituents to be identical or different R2the number of m,
R2is a Deputy, presented on the carbon atom or the nitrogen atom, forms,
R2is a Deputy selected from the group consisting of hydroxy group, halogen atom, cyano group, oxo group, With1-4alkyl groups (where C1-4the alkyl group may be substituted With 11-4alkoxy group) and C1-4alkoxy group, when R2is a Deputy, presented on the carbon atom, forms, and R2is a Deputy selected from the group consisting of C1-4alkyl groups and C1-4alkylcarboxylic group, when R2is a Deputy, presented at the nitrogen atom, forms,
m is any integer from 0 to 2,
Q is a bond or C1-4alkylenes group,
R3and R4are the same or different and represent each a hydrogen atom or halogen atom, and
R5and R6are the same or different, and so is astavliaut them each a hydrogen atom, halogen atom or With1-4alkyl group,
or its pharmacologically acceptable salt.

2. The compound or its pharmacologically acceptable salt according to claim 1, where R3represents a hydrogen atom, a fluorine atom or a chlorine atom, and R4represents a hydrogen atom.

3. The compound or its pharmacologically acceptable salt according to claim 1, where Q is a bond or methylene group.

4. The compound or its pharmacologically acceptable salt according to claim 1, where In is a3-6cycloalkyl group, tetrahydrofuryl group, dihydropyrazolo group, tetrahydropyranyloxy group, dioxinlike group, piperidino group, piperazinilnom group or 1,1-deoxycorticosterone group.

5. The compound according to claim 1, where the compound is any compound selected from:
1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it,
1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it,
6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it,
6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it,
1-[(2S)-1,4-dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridi the-2-it,
2,6-anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol,
2,6-anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol,
2,6-anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b] pyridine-1-yl]-5-O-methyl-L-threo-hexitol,
2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol,
2,6-anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol and
2,6-anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol.

6. 1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it.

7. 1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydroimidazo[4,5-b]pyridine-2-it.

8. 6-(3,4-Dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it.

9. 6-(3-Chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1-[(2S)-1,4-dioxane-2-ylmethyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-it.

10. 1-[(2S)-1,4-Dioxane-2-ylmethyl]-6-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-1,3-dihydro-2H-imidazo[4,5-b]PI is one-2-it.

11. 2,6-Anhydrous-1,3,5-trideoxy-4-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol.

12. 2,6-Anhydrous-1,3,4-trideoxy-5-O-methyl-1-[6-(4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-L-threo-hexitol.

13. 2,6-Anhydrous-1,3,4-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-5-O-methyl-L-threo-hexitol.

14. 2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,4-trideoxy-5-O-methyl-L-threo-hexitol.

15. 2,6-Anhydrous-1,3,5-trideoxy-1-[6-(3,4-dimethyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-4-O-methyl-L-threo-hexitol.

16. 2,6-Anhydrous-1-[6-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl]-1,3,5-trideoxy-4-O-methyl-L-threo-hexitol.

17. Pharmacologically acceptable salt of the compound according to any one of pp.5-16.

18. Pharmaceutical composition having mTOR inhibitory activity, containing the compound or its pharmacologically acceptable salt according to any one of claims 1 to 16 as an active ingredient.

19. The use of compound or its pharmacologically acceptable salt according to any one of claims 1 to 16 as an active ingredient in the manufacture of anti-cancer drugs.

20. The use of compounds or farmacologicas is acceptable salt according to any one of claims 1 to 16 as an active ingredient in the manufacture of an inhibitor of mTOR.

21. The application of claim 20, where the cancer is a leukemia, lymphoma, multiple myeloma, brain tumor, malignant tumor of the head and neck, cancer of the esophagus, cancer of the stomach, apendicular malignant tumor, colon tumor, a malignant tumor of the anal canal malignant tumor of the gallbladder, cancer of the bile ducts, cancer of the pancreas, stromal tumor of the gastrointestinal tract, cancer of the lung, malignant liver tumor, mesothelioma, a malignant tumor of the thyroid gland, cancer of the kidney, cancer of the prostate, neuroendocrine tumor, a melanoma, a malignant tumor breast cancer, cancer of the endometrium, cancer of the cervix, malignant ovarian tumor, osteosarcoma, soft tissue sarcoma, sarcoma Galoshes, myosarcoma, a malignant tumor of the kidney, cancer of the bladder and/or malignant tumors of the testes.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrole nitrogen-containing heterocyclic derivatives of formula (I) or their pharmaceutically acceptable salts:

,

wherein: X means C, N; each R1,R2 means H; R3 means C1-10alkyl; R4 means -[CH2CH(OH)]rCH2NR9R10, -(CH2)nNR9R10; provided X means N, R5 is absent, each R6, R7, R8 means H, halogen; provided X means C, each R5, R6, R7, R8 means H, halogen, hydroxyC1-10alkyl, C1-10alkyl, phenyl, 6-member heteroaryl with one N, -OH, -OR9, -NR9R10, -(CH2)nCONR9R10, -NR9COR10, -SO2R9 and -NHCO2R10, wherein said phenyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, C1-10alkoxyl, halogen; each R9, R10 means H, C1-10alkyl wherein C1-10alkyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, phenyl, halogenophenyl, -OH, C1-10alkoxy, OH- C1-10alkyl; or R9 and R10 together with an attached atom form a 5-6-member heteroring which may contain one O; n is equal to 2- 6; z is equal to 1-2; r is equal to 1-6;.

EFFECT: compounds may be used as protein kinase inhibitors.

14 cl, 2 tbl, 67 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new antibacterial compounds of formula I

wherein R1 represents halogen or alkoxy group; each U and W represents N; V represents CH, and R2 represents H or F, or each U and V represents CH; W represents N, and R2 represents H or F, or U represents N; V represents CH; W represents CH or CRa, and R2 represents H, or also when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents group CH=CH-B, a binuclear heterocyclic system D, phenyl group which is mono-substituted in the position 4 by C1-4 alkyl group, or phenyl group which is di-substituted in positions 3 and 4 wherein each of two substitutes is optionally specified in a group consisting of C1-4 alkyl and halogen; B represents mono- or di-substituted phenyl group wherein each substitute is a halogen atom; D represents group

wherein Z represents CH or N, and Q represents O or S; or to salts of such compounds.

EFFECT: compounds are used for treating bacterial infections.

13 cl, 2 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of antibiotics, which represent compounds of formula (I) and their pharmaceutically acceptable salts, where U, V, W, X, R1, R2, R3, R4, R5, R6, A, B, D, E, G, m and n are determined in description. Invention also relates to pharmaceutical composition, containing said compounds and their application for obtaining medication for prevention or treatment of bacterial infections.

EFFECT: obtaining useful antimicrobial agents, efficient against various pathogens of people and animals.

23 cl, 1 tbl, 186 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to anhydrous crystalline vinflunine salts of general formula (I) prepared with 1 or 2 equivalents of a pharmaceutically acceptable inorganic or organic acid. . In formula (I) [The acid] represents hydrobromic, lactic or fumaric acid for a group of water-soluble crystalline salts, as well as para-toluenesulphonic, benzoic, mandelic and para-hydroxybenzoic acid for a group of relatively water-insoluble crystalline salts.

EFFECT: preparing the anhydrous crystalline vinflunine salts.

8 cl, 8 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel azaindole derivatives, having JAK-2 and JAK-3 kinase inhibiting activity, or pharmaceutically acceptable salts thereof. In formula (I): R3 denotes H; X1 denotes N or CR4; R2 denotes H, COOH, COOR' or CONHR'; R4 denotes H, F, R, OH, OR', COR', COOH, COOR', CONH2 or CN; or R2 and R4, taken together, form a benzene ring optionally substituted with 1-2 R10; R' denotes C1-3-alkyl or C1-3-alkenyl, each optionally substituted 1-2 R5; each R5 is independently selected from CN, unsubstituted C1-2alkyl, or two groups R5 together with a carbon atom with which they are bonded form a cyclopropyl ring; each R10 is independently selected from halogen, OCH3 or OH; R1 denotes or , R is H or denotes C1-2alkyl, optionally substituted with 1-3 R11; R6 denotes C1-4alkyl, optionally substituted with 1-5 R12; values of radicals R7 -R9, ring A, R11 -R14. The invention also relates to a pharmaceutical composition containing said compounds and a method of treating or reducing severity of a pathological condition such as allergy, asthma, amyotrophic lateral sclerosis, multiocular sclerosis, graft rejection, rheumatoid arthritis, solid malignant tumour, haematologic malignant disease, leukaemia, lymphoma and myeloproliferative disorders.

EFFECT: high efficiency of using the compounds.

41 cl, 6 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to substituted imidazopyridine derivatives of general formula (I) or enantiomers, diastereomers and tautomers and pharmaceutically acceptable salts thereof, in which A denotes -NH-, -CH2-, -CH2-CH2- or a bond; X denotes phenyl, phenyl condensed with a saturated heterocyclic 5- or 6-member ring, where the heterocyclic ring can contain one or two heteroatoms selected from O and N, and where the heterocyclic ring can further be substituted with an oxo group, a 6-member saturated heterocyclyl containing O as a heteroatom, a 5-6-member heteroaryl containing 1 or 2 heteroatoms selected from N, O and S, and where each phenyl and heteroaryl is possibly substituted with 1 to 2 R14 and/or 1 substitute R4b and/or 1 substitute R5; R1 and R2 are independently selected from the following groups: C1-6-alkyl and C1-6-alkylene-C3-7-cycloalkyl, and where each alkyl is possibly substituted with a OH group, or R1 and R2 together with the nitrogen atom with which they are bonded form a 5-6-member ring which is possibly substituted with one substitute selected from C1-6-alkyl and O-C1-6-alkyl; R4b denotes C(O)NH2, C(O)OH, C(O)NH-C1-6-alkyl, C(O)N-(C1.6-alkyl)2, SO2-C1-6-alkyl, oxo group, and where the ring is at least partially saturated, NH2, NH-C1-6-alkyl, N-(C1-6-alkyl)2; R5 denotes a 6-member heteroaryl containing N as a heteroatom; R3 denotes -(CR8R9)n-T; R8 and R9 are independently selected from the following groups: H and C1-6-alkyl; n equals 1, 2, 3, 4, 5 or 6; T denotes or NR12R13; R10 denotes H, NH2, OH, C1-6-alkyl, possibly substituted with one OH, a halogen atom, NH(C1-6-alkyl) or N(C1-6-alkyl)2; q equals 1 or 2; Y denotes CH2, NR11 or O; R11 denotes H, or C1-6-alkyl; R12 and R13 are independently selected from the following groups: H, C1-6-alkyl, C1-6-alkynyl, (CH2)0-2-C3-7-cycloalkyl, and C1-6-alkylene-O- C1-6-alkyl, where C1-6-alkyl is possibly substituted with one halogen; R14 denotes a halogen atom, CN, C1-6-alkyl, possibly substituted with 1-3 substitutes selected from halogen atom, OH, O- C1-6-alkyl, O-C(O)C1-6-alkyl, O- C1-6-alkyl, possibly substituted with one substitute selected from OH, O- C1-6-alkyl, and O-C(O) C1-6-alkyl, or OH. The invention also relates to a pharmaceutical composition based on the compound of formula (I).

EFFECT: novel imidazopyridine derivatives are obtained, which can be used as melanocortin-4 receptor modulators.

17 cl, 8 tbl, 22 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new compounds of formula , wherein A represents residues of formulae

, , , X represents O; X1-X4 represents N, CH, CR1 or C-, X9-X12 represents N, CH, CR4 or C-, X13-X16 represents N, CH, CR or C-, wherein C represents an attachment point of the group A to a residue of the structure of formula (I); R' represents H or alkyl; R represents alkoxy, or Het; R1 represents F, CI, Br, I, OH, CN, carboxy, CONR6R7, NR2COR8, NR2COOR8, alkoxy, fluorinated alkoxy, Ar, Het or OHet; or R1 represents one of the following formulas: wherein n is equal to 2 and m is equal to 3; R2 represents H, alkyl, fluorinated alkyl, cycloalkyl, Het or Het-NH-CO-; R4 represents F, Cl, Br, I, OH, alkoxy, cycloalkoxy, Het or OHet; or R4 represents one of the following formulae: , wherein n is equal to 2 and t is equal to 3; each R6 and R7 independently represents alkyl, or cycloalkyl, or R6 and R7 together represent alkylene group containing 5-6 carbon atoms which forms a cycle with N atoms; R8 represent alkyl, or cycloalkylalkyl; R9 represents alkyl; Ar represents aryl group; Het represents heterocyclic group which is completely saturated, particularly saturated or completely unsaturated containing 5 to 10 ring atoms in which at least 1 ring atom represents N, O or S atom which is unsubstituted or substituted once or several times by the substituted specified in cl. 1; and their pharmaceutically acceptable salts or solvates or N-oxides, or solvates of their pharmaceutically acceptable salts, or solvates of N-oxides of their pharmaceutically acceptable salts wherein said compound can be presented in the form of a polymorph, wherein if said compound shows chirality, it can be presented in the form of a mixture of enanthiomers or a mixture of diastereoisomers, or can be presented in the form of single enanthiomer or single diastereoisomer; and wherein at least one of the groups R, R1 or R4 represents Het or OHet, wherein the group Het is specified in each case in substituted or unsubstituted azabicyclooctyl, oxaazabicycloheptyl, diazabicycloheptyl, diazabicyclononyl, diazabicyclooctyl, pyrazolyl, dihydroimidazolyl, 1,4-diazepanyl, hezahydropyrrolopyrazinyl and octahydropyrrolopyridinyl. Also the invention refers to other compounds of formula (I), to specific compounds, to a pharmaceutical composition based on the compound of formula (I), to a method of selective activation/stimulation of α-7 nicotinic receptors, to application of the compound of formula (I) for making the drug.

EFFECT: there are produced new compounds showing effective biological properties.

53 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present application describes substituted bicyclic beta-lactams of formula I: which are class A and class C β-lactamase inhibitors wherein X, R1 and R2 are specified in the application, as well as a method for producing them. The compounds of formula I and their pharmaceutically acceptable salts are applicable for preparing a pharmaceutical composition and for producing a drug. The declared compounds are applicable for treating bacterial infections, optionally in a combination with a β-lactam antibiotic. Particularly, the compounds may be used with such β-lactam antibiotics, as e.g. imipenem, piperacillin or ceftazidime to control microorganisms resistant to β -lactam antibiotics due to the presence of β-lactamases.

EFFECT: preparing the composition for treating bacterial infections.

28 cl, 117 ex, 3 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae

and ,

which can be used to inhibit lipid kinase, including PI3K, and treat lipid kinase-mediated disorders. Values of radicals are given in claim 1.

EFFECT: improved properties of the compound.

11 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae and including their stereoisomers, as well as pharmaceutically acceptable salt, where X denotes O or S; R1 is selected from H, F, CI, Br, I, CN, -CR14R15-NR16R17, -CR14R15-NHR10, -(CR14R15)NR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10)R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NHR12, -NR12C(=Y)R10, -S(O)2R10, -S(O)2NR10R11, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C4 carbocyclyl, piperidinyl, thiopyranyl, phenyl or C5-C6 heteroaryl; R2 is selected from H, C2-C12 alkyl and thiazolyl; R3 denotes a condensed bicyclic heteroaryl selected from indazole, indole, benzoimidazole, pyrrolopyridine, imidazopyridine and quinoline; R10, R11 and R12 independently denote H, C2-C12 alkyl, C3 carbocyclyl, heterocyclyl selected from pyrrolidine, morpholine and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine, benzothiophene; or R10 and R11 together with a nitrogen atom with which they are bonded possibly form a saturated C3-C6 heterocyclic ring, possibly containing one additional ring atom selected from N or O, where said heterocyclic ring is possibly substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10, C(=O)R10, NR12S(O)R11, C(=Y)NR10R11, C1-C12 alkyl and heterocyclyl selected from pyrrolidine; R14 and R15 are independently selected from H or C1-C12 alkyl; R16 and R17 independently denote H or phenyl; R18 and R19 together with a carbon atom with which they are bonded form a C3-C20 heterocyclic ring, where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted with one or more groups independently selected from F, CI, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11, possibly substituted with carbocyclyl, selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted with alkyl and alkylsulphonyl, pyrrolidine, morpholine, piperdine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole; Y denotes O; m equals 0, 1 or 2; n equals 1 and t equals 2. The invention also relates to a pharmaceutical composition which modulates lipid kinase activity, based on said compounds.

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used to treat lipid kinase-mediated diseases, for example, cancer.

48 cl, 2 tbl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazo[4,5-b]pyrazine derivatives of general formula or to its pharmaceutically acceptable salt wherein: R1 represents either aryl unsubstituted or substituted by one of the groups: halogen, hydoxyl, C1-6alkyl, C1-6alkoxyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, NHC1-6alkylC1-6alkoxy, C1-6alkylhydroxy, -C(O)NH2, -C(O)OC1-6alkyl, -C(O)NH C1-6alkyl, cyano, carboxy, heteroaryl and heterocycloalkyl; or heteroaryl unsubstituted or substituted by one of the groups: C1-6alkoxy, hydroxy, -C1-6alkyl, NH2 and NHC1-6alkyl; heterocycloalkyl unsubstituted or substituted by one group =O; and R2 represents H; unsubstituted C3-4alkyl; C1-4alkyl substituted by C5-6cycloalkyl unsubstituted or substituted by one group specified in amino, hydroxyl, C1-6alkoxy, or heterocycloalkyl unsubstituted or substituted by 1-2 groups specified in =O, C1-6alkyl; or C5-6cycloalkyl substituted by one group specified in hydroxyl, C1-6alkoxyl, C1-6alkylC1-6alkoxy, C1-6alkylhydroxy, CONH2; or substituted ir unsubstituted heterocycloalkyl; wherein aryl represents an aromatic structure consisting of 6-10 carbon atoms containing one ring or two condensed rings; wherein heteroaryl represents a 5-10-member aryl ring system containing 1-2 heteroatoms specified in nitrogen, oxygen and sulphur; wherein heterocycloalkyl represents a 5-9-member nonaromatic cycloalkyl wherein 1-2 heteroatoms specified in nitrogen and oxygen; provided the compound does not represent 1,3-dihydro-5-phenyl-2H-imidazo[4,5-b]pyrazin-2-one. Also, the invention refers to the specific imidazo[4,5-b]pyrazine derivatives, to a based pharmaceutical composition, to a method of treating or preventing cancer, inflammatory conditions, immunological diseases, metabolic conditions, and to a method of kinase inhibition in a cell expressing said kinase.

EFFECT: there are produced new imidazo[4,5-b]pyrazine derivatives showing effective biological properties.

17 cl, 2 tbl, 210 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and

possessing the protein kinase inhibitor property, their pharmaceutically acceptable salts, solvates and hydrates, as well as to the use thereof and a based pharmaceutical composition. In general formula (1) X1 represents N, CRt1; X2 represents N, CRt2, X3 represents N, CRt3, X4 represents N, CH and wherein X1, X2, X3 and X4 are independently specified; Rt1 represents -H, halogen, -COOH, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -CN, -CH3OH; Rt2 represents -H, halogen, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -CN, CH2OH, -NH2; Rt3 represents -H, -S(O)rR4, halogen, -CN, -COOH, -CONH2, -COOCH3, -COOCH2CH3; the cycle A represents phenyl or a 6-member heteroaryl cycle, wherein heteroaryl contains 1-2 heteroatoms specified in N optionally substituted by 1-4 groups R'; the cycle B represents phenyl or a 5- or 6-member heteroaryl cycle, wherein heteroaryl contains 1-2 heteroatoms specified in N, S optionally substituted by 1-5 groups Rb; Ra and Rb are independently specified and represent -H, halogen, -CN, -R6, -OR4, -NR4R5, -C(O)YR4, -S(O)rR4, -SO2NR4R5, -NR4SO2NR4R5 wherein Y is independently specified and represents a chemical bond, -O-, -S-, -NR3-; L1 represents NR3C(O) or C(O)NR3; R3, R4 and R5 are independently specified and represent H, C1-C6-alkyl, and also the group NR4 R5 may represent a 5- or 6-member saturated or aromatic cycle; in each case R6 is independently specified and represents C1-C6-alkyl optionally substituted by C1-C6- alkyl or 5-6 merous heterocyclyl which may be substituted by C1-C6-alkyl; r is equal to 0; In general formula (II) Z represents CH; X, represents CRt1; X2 represents CRt2, X3 represents CRt3 X4 represents CH and wherein X1, X2, X3 and X4 are independently specified; Rt1 represents -H; Rt2 represents -H, -F; Rt3 represents -H, -F; the cycle A represents phenyl or 6-member heteroaryl cycle wherein heteroaryl contains 1-2 heteroatoms specified in N optionally substituted by 1-4 groups R3; the cycle B represents phenyl or a 5- or 6-member heteroaryl cycle wherein heteroaryl contains 1-2 heteroatoms specified in N, S optionally substituted by 1-5 groups Rb, Ra and Rb are independently specified and represent -H, halogen, -CN, -R6, -OR4, -NR4R5, -C(O)YR4, -S(O)rR4, -SO2NR4R5 wherein Y is independently specified and represents a chemical bond, -NR3-; L represents NR3C(O) or C(O)NR3; R4 and R5 are independently specified and represent H, C1-C6-alkyl, also the group NR4R3 may represent a 6-member saturated cycle; in each case R6 is independently specified and represents, C1-C6-alkyl optionally substituted by C1-C6-alkyl or 5-6 member heterocyclyl which may be substituted by C1-C6-alkyl; r is equal to 0; m is equal to 1; p is equal to 1.2.

EFFECT: preparing the compounds possessing the protein kinase inhibitor property.

16 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylpyrrolidinyl methylpyrrolidine amides of formula , where R, R1, R2 and R3 are identical or different and independently denote H, (C1-C4)alkyl, CF3; R4 denotes phenyl, cyclohexyl, pyridinyl, furanyl, isoxazolyl, quinolinyl, naphthyridinyl, indolyl, benzoimidazolyl, benzofuranyl, chromanyl, 4-oxo-4H-chromenyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxolyl and 2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e]][1,4]diazepinyl; where said R4 is optionally substituted one to more times with a substitute selected from halogen, hydroxy, (C1-C4) alkyl, (C1-C4) alkoxy, CF3, hydroxymethyl, 2-hydroxyethylamino, methoxyethylamide, benzyloxymethyl, piperidinyl, N-acetylpiperidinyl, pyrrolyl, imidazolyl, 5-oxo-4,5-dihydropyrazolyl; or pharmaceutically acceptable salt thereof or enantiomer or diastereomer thereof.

EFFECT: compounds have modulating activity on histamine H3 receptor, which enables use thereof to prepare a pharmaceutical composition.

10 cl, 3 dwg, 29 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where values of R, R1, R2, R3 and R4 are given in claim 1.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof in pharmaceutical compositions for treating sleep disorder.

10 cl, 1 tbl, 4 dwg, 153 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to (aza)indole derivatives of formula

wherein the values T, X1-X3, R1, Q, Y, J are presented in clause 1 of the patent claim.

EFFECT: compounds possess xanthine oxidase inhibitory action that enables using it in a pharmaceutical composition for treating a disease specified in a group consisting of hyperuricemia, gouty tophus, gouty arthritis, renal diseases associated with hyperuricemia and nephrolithiasis.

19 cl, 62 tbl, 332 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel derivatives of imidazo[4,5-c]chinoline of general formula or to its pharmaceutically acceptable salts, where R1 represents straight-chained C1-C6alkyl, possibly substituted with one substituent, selected from C1-C3alkoxy; Z1 represents C2-C6alkylene; X1 represents NR5 or >NCOR5; Y1 represents C1-C6alkylene; R3 represents C1-C6alkyl, possibly substituted with C1-C6alkoxy; R5 represents hydrogen, piperidinyl, possibly substituted by piperidinyl nitrogen with group R10, group C1-C6alkyl, where the last group is possibly substituted with one substituent, independently selected from NR7R8 or R9; or R5 represents C1-C6alkylene, which can be bound with carbon atom in C2-C6alkylene group Z1 with formation of piperidine ring; each of R7 and R8 independently represents tetrahydropyranyl, piperidinyl, possibly substituted by piperidinyl nitrogen atom with group R10a, C1-C6alkyl, where the last group is possibly substituted with one group, independently selected from OR12; or R7 and R8 together with nitrogen atom, to which they are bound, form 4-7-membered saturated heterocyclic ring, selected from asetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, 1,4-oxazepanyl and 1,4-diazepanyl, where heterocyclic ring is possibly substituted with one or two substituents, independently selected from S(O)qR15, OR15, CO2R15, COR15, CONR15R16, NR15CO2R16, pyrimidinyl and C1-C6alkyl, where the last group is possibly substituted with one group, independently selected from OR18 and CO2R18; R9 represents S(O)qR20; R10 and R10a independently represent COR2 or group C1-C6alkyl; each of R12, R15, R16, R18, R20 and R24 independently represents hydrogen or C1-C6alkyl; q equals 2; m and n both equal 0; and A represents phenyl. Invention also relates to method of obtaining formula (I) compound, based on it pharmaceutical composition, and to method of treating said pathological conditions.

EFFECT: obtained are novel derivatives of imidazo[4,5-c]chinoline, useful modulation of TLR7 activity.

17 cl, 18 dwg, 81 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel heterocyclic amide compound of formula I: or a pharmaceutically acceptable salt thereof. Described also is a pharmaceutical composition containing said compound, having protein kinase inhibitor, regulator or modulator properties, which is acceptable in treating or preventing a proliferative disease, an anti-proliferative disorder, inflammation, arthritis, neurologic or neurodegenerative disease, cardiovascular disease, hair loss, neural disease, ischemic disorder, viral disease or fungal disease.

EFFECT: high efficiency of using the compounds.

2 cl, 20 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrole nitrogen-containing heterocyclic derivatives of formula (I) or their pharmaceutically acceptable salts:

,

wherein: X means C, N; each R1,R2 means H; R3 means C1-10alkyl; R4 means -[CH2CH(OH)]rCH2NR9R10, -(CH2)nNR9R10; provided X means N, R5 is absent, each R6, R7, R8 means H, halogen; provided X means C, each R5, R6, R7, R8 means H, halogen, hydroxyC1-10alkyl, C1-10alkyl, phenyl, 6-member heteroaryl with one N, -OH, -OR9, -NR9R10, -(CH2)nCONR9R10, -NR9COR10, -SO2R9 and -NHCO2R10, wherein said phenyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, C1-10alkoxyl, halogen; each R9, R10 means H, C1-10alkyl wherein C1-10alkyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, phenyl, halogenophenyl, -OH, C1-10alkoxy, OH- C1-10alkyl; or R9 and R10 together with an attached atom form a 5-6-member heteroring which may contain one O; n is equal to 2- 6; z is equal to 1-2; r is equal to 1-6;.

EFFECT: compounds may be used as protein kinase inhibitors.

14 cl, 2 tbl, 67 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 2-heteroaryl-substituted benzothiophene and benzofuran, precursors thereof and therapeutic use of said compounds, having structural formula (1a) where R1, R2, X9 and Q assume values given in the description, and pharmaceutically acceptable salts thereof, which are suitable for imaging amyloid deposits in living patients. The invention also relates to pharmaceutical compositions based on compounds of formula 1a, use and methods of producing said compounds. More specifically, the present invention relates to a method of imaging brain amyloid deposits in vivo for intravital diagnosis of Alzheimer's disease, and measuring clinical efficiency of therapeutic agents against Alzheimer's disease.

EFFECT: high efficiency of using said compounds.

15 cl, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (IX) wherein radicals and symbols have values given in the claim, and pharmaceutically acceptable salts or tautomers thereof. Said compounds are inhibitors of poly(ADP-ribose)polymerase (PARP) and can be used to treat cancer, inflammatory diseases, reperfusion injuries, ischaemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, retroviral infections, retinal damage, skin senescence and UV-induced skin damage, and as chemo- or radiosensitisers for cancer treatment. The invention also relates to a pharmaceutical composition containing said compounds, use of said compounds and a method of treating said diseases.

EFFECT: high efficiency of using the compounds.

10 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to production of sterol derivatives, and can be used in producing 4-hydroxy-17R-methylincisterol from ergosterol by photoisomeration. When carrying out the method, a weighed portion of ergosterol is dissolved in a weakly polar solvent while illuminating the solution with optical radiation in the near UV range. The obtained solution is chromatographically separated. The fraction which is cytotoxic for HeLa line of cancer cells and human myeloid leukaemia cells is sorbed. The pH is raised to neutral value and the solution is evaporated until a milky appearance is achieved. The weakly polar solvent is added and extracted, and the organic layer is separated on separating funnel. The organic layer is evaporated and dissolved. The obtained solution is separated by analytical HPLC with subsequent purification and separation of incisterol.

EFFECT: invention enables to obtain a 4-hydroxy-17R-methylincisterol preparation by chemical synthesis.

10 cl

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