Imidazole derivatives and their use as modulators of cyclin dependent kinases

• US 8,598,217 B2
• Filed: 04/30/2010
• Issued: 12/03/2013
• Est. Priority Date: 04/30/2009
• Status: Expired due to Fees

• Current Assignee: Novartis Ag, Astex Therapeutics Limited (Otsuka Holdings Company Limited)
• Original Assignee: Novartis Ag, Astex Therapeutics Limited (Otsuka Holdings Company Limited)
• Inventors: Howard, Steven, Mortenson, Paul Neil, Woolford, Alison Jo-Anne, Woodhead, Andrew James, Chessari, Gianni, O'Reilly, Marc, Congreve, Miles Stuart, Dagostin, Claudio, Cho, Young Shin, Chen, Christine Hiu-Tung, Brain, Christopher Thomas, Lagu, Bharat, Wang, Yaping, Luzzio, Michael Joseph, Perez, Lawrence Blas, Hiscock, Steven Douglas, Yang, Fan, Kim, Sunkyu, Giraldes, John
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Neagu, Irina
• Application Number:
  US13/266,976
• Publication Number:
  US 20120101064A1
• Time in Patent Office: 1,313 Days
• Field of Search: 514/396, 514/397, 514/399, 514/400, 514/303, 514/341, 514/394, 514/365, 514/253.05, 514/253.09, 514/234.5, 514/318, 514/319, 514/322, 514/323, 514/307, 514/218, 514/81, 544/364, 544/139, 544/131, 544/363, 546/274.7, 546/273.1, 546/118, 546/144, 546/199, 548/303.1, 548/312.1
• US Class Current: 514/396
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 233/22 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 233/24 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 235/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 : Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The invention provides compounds of the formula (I):

and salts, tautomers, solvates and N-oxides thereof;
wherein Q is CH or N; X is N, N⁺—O⁻ or CR³; Y is N, N⁺—O⁻ or CR^3a; R¹ and R² are independently selected from hydrogen and various substituents as defined in the claims; or R¹ and R² together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R³ is selected from hydrogen and various substituents; and R^3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.

Claims

1. A compound of the formula (I):

2. A compound of the formula (I) according to claim 1, or a salt, tautomer, solvate or N-oxide thereof,

wherein:

X is N, N⁺—

O⁻

or CR³;

Y is N, N⁺—

O⁻

or CR^3a;

R¹ and R² are independently selected from hydrogen;

halogen;

cyano;

hydroxyl;

C_1-8 alkyl;

C_1-8 alkoxyl;

C_2-8 alkenyl;

C_2-8 alkynyl;

C_3-8 cycloalkyl;

C_2-8 cycloalkenyl;

aryl;

heterocyclyl;

heteroaryl;

OR⁵;

C═

OR⁵;

C═

OOR⁵;

OC═

OR⁵;

S(O)_nR⁵;

NR⁷R⁸;

NR⁷C═

OR⁸;

C═

ONR⁷R⁸;

SO₂NR⁹R¹⁰;

wherein the C_1-8 alkyl, C_1-8 alkoxyl, C_2-8 alkenyl and C_2-8 alkynyl moieties are each optionally substituted by one or more substituents R¹¹; and

the C_3-8 cycloalkyl, C_2-6 cycloalkenyl, aryl, heterocyclyl and heteroaryl are each optionally substituted by one or more substituents R¹²;

n is 0, 1 or 2;

m is 0, 1, 2, or 3;

or R¹ and R² together with the atoms to which they are attached, link to form an aromatic or non-aromatic ring of 4 to 7 members, wherein said aromatic or non-aromatic ring contains 0, 1 or 2 heteroatom ring members selected from O, N and S, wherein the aromatic or non-aromatic ring is optionally substituted by one or more substituents R¹³;

R³ is selected from hydrogen;

halogen;

cyano;

OR⁵;

C═

OR⁵;

OC═

OR⁵;

C═

OOR⁵;

S(O)_nR⁵;

NR⁷R⁸;

NR⁷C═

OR⁸;

C═

ONR⁷R⁸;

SO₂NR⁹R¹⁰;

C_1-6 alkyl;

C_2-6 alkenyl;

C_2-6 alkynyl;

C_3-6 cycloalkyl;

5 or 6 membered aryl; and

5 or 6 membered heteroaryl;

R^3a is selected from hydrogen;

halogen;

cyano;

OR⁵;

C═

OR⁵;

OC═

OR⁵;

C═

OOR⁵;

S(O)_nR⁵;

NR⁷R⁸;

NR⁷C═

OR⁸;

C═

ONR⁷R⁸;

SO₂NR⁹R¹⁰;

C_1-6 alkyl;

C_2-6 alkenyl;

C_2-6 alkynyl;

C_3-6 cycloalkyl;

5 or 6 membered aryl; and

5 or 6 membered heteroaryl;

wherein, in R³ and R^3a, the C_1-8 alkyl, C_1-8 alkoxyl, C_2-6 alkenyl and C_2-6 alkynyl moieties are each optionally substituted by one or more substituents R¹¹; and

the C_3-6 cycloalkyl, 5- or 6-membered aryl, and 5- or 6-membered heteroaryl moieties are each optionally substituted by one or more substituents R¹²;

R⁵ is selected from C_1-8 alkyl;

C_3-8 cycloalkyl;

aryl;

heteroaryl; and

heterocyclyl;

R⁷ and R⁸ are the same or different, and independently are selected from hydrogen;

C_1-8 alkyl;

C_3-8 cycloalkyl;

aryl;

heteroaryl; and

heterocyclyl;

or NR⁷R⁸ forms a non-aromatic four to seven membered ring optionally containing a second heteroatom selected from O, N and S, and optionally substituted by one or more substituents R¹²;

R⁹ and R¹⁰ are the same or different, and independently are selected from hydrogen;

C_1-8 alkyl;

C_3-8 cycloalkyl;

aryl;

heteroaryl; and

heterocyclyl;

or NR⁹R¹⁰ forms a non-aromatic four to seven membered ring optionally containing a second heteroatom selected from O, N and S, and optionally substituted by one or more substituents R¹²;

wherein, in R⁵, R⁷, R⁸, R⁹, and R¹⁰, the C_1-8 alkyl moiety is optionally substituted by one or more substituents R¹¹; and

the C_3-8 cycloalkyl, aryl, heteroaryl and heterocyclyl moieties are each optionally substituted by one or more substituents R¹²;

R¹¹ is selected from the group consisting of halogen;

cyano;

═

O;

hydroxyl;

C_1-6 alkyl;

C_1-6 alkoxy;

C_2-6 alkenyl;

C_2-6 alkynyl;

C_3-6 cycloalkyl;

C_3-6 cycloalkenyl;

aryl;

heteroaryl;

heterocyclyl;

—

(CH₂)_m—

NR^7aR^8a;

—

(CH₂)_m—

COOR^5a;

—

(CH₂)_m—

OC═

OR^5a;

—

(CH₂)_m—

C═

OR^5a;

—

(CH₂)_m—

S(O)_nR⁵;

—

(CH₂)_m—

NR^7aC═

OR^8a;

—

(CH₂)_m—

C═

ONR^7aR^8a;

—

(CH₂)_m—

SO₂NR^9aR^10a;

—

(CH₂)_m-aryl;

—

(CH₂)_m—

O-aryl;

—

O—

(CH₂)_m-aryl;

—

(CH₂)_m-heterocyclyl;

—

O—

(CH₂)_m-heterocyclyl; and

—

(CH₂)_m—

O-heterocyclyl;

R¹² is selected from the group consisting of halogen;

cyano;

═

O;

hydroxyl;

C_1-6 alkyl;

C_1-6 alkoxyl;

C_2-6 alkenyl;

C_2-6 alkynyl;

C_3-6 cycloalkyl;

C_3-6 cycloalkenyl;

—

(CH₂)_m—

NR^7aR^8a;

—

(CH₂)_m—

COOR^5a;

—

(CH₂)_m—

OC═

OR^5a;

—

(CH₂)_m—

C═

OR^5a;

—

(CH₂)_m—

S(O)_nR^5a;

—

(CH₂)_m—

NR⁷C═

OR^8a;

—

(CH₂)_m—

C═

ONR^7aR^8a;

—

(CH₂)_m—

SO₂NR^9aR^10a;

—

(CH₂)_m-aryl;

—

(CH₂)_m—

O-aryl;

—

O—

(CH₂)_m-aryl;

—

(CH₂)_m-heterocyclyl;

—

O—

(CH₂)_m-heterocyclyl; and

—

(CH₂)_m—

O-heterocyclyl;

wherein, in R¹¹ and R¹², the C_1-6 alkyl, C_1-6 alkoxyl, C_2-6 alkenyl and C_2-6 alkynyl moieties are each optionally substituted by one or more substituents R¹⁴; and

the C_3-8 cycloalkyl, O_3-6 cycloalkenyl, aryl, heterocyclyl and heteroaryl moieties are each optionally substituted by one or more substituents R¹⁵;

R¹³ is selected from the group consisting of halogen;

cyano;

hydroxyl;

═

O;

an oxide (when R¹³ is attached to N or S);

a dioxide (when R¹³ is attached to S);

C_1-6 alkyl optionally substituted by one or more substituents R¹¹;

C_1-6 alkoxyl optionally substituted by one or more substituents R¹¹;

C_2-6 alkenyl optionally substituted by one or more substituents R¹¹;

C_2-6 alkynyl optionally substituted by one or more substituents R¹¹;

C_3-6 cycloalkyl optionally substituted by one or more substituents R¹²;

C_3-8 cycloalkenyl optionally substituted by one or more substituents R¹²;

aryl optionally substituted by one or more substituents R¹²;

heteroaryl optionally substituted by one or more substituents R¹²;

heterocyclyl optionally substituted by one or more substituents R¹²;

(CH₂)_m—

NR⁷R⁸;

—

(CH₂)_m—

COOR⁵;

—

(CH₂)_m—

OC═

OR⁵;

—

(CH₂)_m—

C═

OR⁵;

—

(CH₂)_m—

S(O)_nR⁵;

—

(CH₂)_m—

NR⁷C═

OR⁸;

—

(CH₂)_m—

C═

ONR⁷R⁸;

—

(CH₂)_m—

SO₂NR⁹R¹⁰;

—

(CH₂)_m-aryl;

—

(CH₂), —

O-aryl;

—

O—

(CH₂)_m-aryl;

—

(CH₂)_m-heterocyclyl;

—

O—

(CH₂)_m-heterocyclyl; and

—

(CH₂)_m—

O-heterocyclyl wherein the aryl or heterocyclyl can be optionally substituted by one or more substituents R¹²; and

Ar is selected from 6-membered aryl optionally substituted by one or more substituents R¹³;

5 or 6-membered heteroaryl optionally substituted by one or more substituents R¹³;

bicyclic aryl optionally substituted by one or more substituents R¹³; and

bicyclic heteroaryl optionally substituted by one or more substituents R¹³;

R¹⁴ is selected from hydroxy;

halogen;

cyano;

C_1-4 alkyl;

C_1-4 alkoxy;

C_1-4 alkoxy-C_2-4 alkoxy;

hydroxy-C_2-4 alkoxy;

(CH₂), NR^7aR^8a;

—

(CH₂)_m—

COOR^5a;

—

(CH₂)_m—

OC═

OR^5a;

—

(CH₂)_m—

C═

OR^5a;

—

(CH₂)_m—

S(O)_nR^5a;

—

(CH₂)_m—

NR^7aC═

OR^8a;

—

(CH₂)_m—

C═

ONR^7aR^8a; and

—

(CH₂)_m—

SO₂NR^9aR^10a;

R¹⁵ is selected from hydroxy;

halogen;

cyano;

C_1-4 alkyl;

C_1-4 alkoxy;

C_1-4 alkoxy-C_2-4 alkoxy;

hydroxy-C_2-4 alkoxy;

(CH₂), NR^7aR^8a;

—

(CH₂)_m—

COOR^5a;

—

(CH₂)_m—

OC═

OR^5a;

—

(CH₂)_m—

C═

OR^5a;

—

(CH₂)_m—

S(O)_nR^5a;

—

(CH₂)_m—

NR^7aC═

OR^8a;

—

(CH₂)_m—

c ═

ONR^7aR^8a; and

—

(CH₂)_mSO₂NR^9aR^10a;

R^5a is selected from C_1-8 alkyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkoxy, halogen and cyano;

C_3-8 cycloalkyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

aryl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

heteroaryl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano; and

heterocyclyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

R^7a and R^8a are the same or different, and independently are selected from hydrogen;

C_1-8 alkyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkoxy, halogen and cyano;

C_3-8 cycloalkyl optionally substituted by one or more substituents hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

aryl optionally substituted by one or more substituents hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

heteroaryl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano; and

heterocyclyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

or NR^7aR^8a forms a non-aromatic four to seven membered ring optionally containing a second heteroatom selected from O, N and S, and optionally substituted by one or more substituents selected from hydroxyl, C_1-4 alkyl, C_1-4 acyl, C_1-4 alkoxycarbonyl and C_1-4 alkylsulphonyl; and

R^9a and R^10a are the same or different, and independently are selected from hydrogen;

C_1-8 alkyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkoxy, halogen and cyano;

C_3-8 cycloalkyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

aryl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano;

heteroaryl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano; and

heterocyclyl optionally substituted by one or more substituents selected from hydroxy, C_1-4 alkyl, C_1-4 alkoxy, halogen and cyano.

3. A compound according to claim 1 wherein Q is CH, Y is CH and X is N or C—

CN.

4. A compound according to claim 1 wherein Ar is selected from phenyl;

naphthyl;

5-membered heteroaryl rings containing a nitrogen ring member and optionally a further heteroatom ring member selected from O, N and S;

6-membered heteroaryl ring rings containing one or two nitrogen ring members;

bicyclic heteroaryl rings containing 9 or 10 ring members of which one or two are heteroatoms selected from O, N and S;

each of the moieties Ar being optionally substituted by one or more substituents R¹³.

5. A compound according to claim 4 wherein Ar is selected from phenyl, pyridyl, pyrazolyl, imidazolyl, thiazolyl, pyrimidinyl, naphthyl, isoquinolinyl, benzoimidazolyl, azobenzoimidazolyl, pyridopyrazolyl, quinolinyl, indolyl, azaindolyl, isoquinolinyl, and 2,3-dihydrobenzfuranyl, each optionally substituted by one or more substituents R¹³.

6. A compound according to claim 5 wherein Ar is an isoquinolinyl ring optionally substituted by one or more substituents R¹³, a pyrazolyl ring optionally substituted by one or more substituents R¹³ or an azaindolyl ring optionally substituted by one or more substituents R¹³.

7. A compound according to claim 1 wherein R¹ and R² together with the carbon atoms to which they are attached form a 6-membered aromatic ring optionally containing one or two nitrogen ring members, and optionally substituted by one or more substituents R¹³.

8. A compound according to claim 7 wherein R¹ and R² together with the carbon atoms to which they are attached form a benzene ring optionally substituted by one or more substituents R¹³ or a pyridine ring optionally substituted by one or more substituents R¹³.

9. A compound according to claim 7 wherein one or two substituents R¹³ are present and are selected from the group consisting of halogen;

cyano;

hydroxyl;

C_1-6 alkyl optionally substituted by one or more substituents R¹¹;

C_1-6 alkoxyl optionally substituted by one or more substituents R¹¹;

heteroaryl optionally substituted by one or more substituents R¹²;

heterocyclyl optionally substituted by one or more substituents R¹²;

(CH₂)_m—

NR⁷R⁸; and

—

(CH₂)_m—

C═

ONR⁷R⁸.

10. A compound according to claim 2 having the formula (II):

11. A compound according to claim 10 having the formula (IIa):

12. A compound according to claim 1 having the formula (IIb):

13. A compound according to claim 1 having the formula (III):

14. A compound according to claim 10 having the formula (IV):

15. A compound according to claim 1 wherein one substituent R¹³ is selected from:

(a) —

O_m—

(C_1-4-alkylene)_n-[Sol], where m is 0 or 1 and n is 0 or 1 and the alkylene is straight chain or branched, provided that when m and n are both 1 and Sol is linked by a nitrogen atom to C_1-4-alkylene, there must be at least two carbon atoms in the C_1-4-alkylene in line between O and [Sol];

(b) —

(C═

O)-[Sol];

(c) (SO₂)-[Sol]

(d) mono- or dihydroxy-C_2-4-alkoxy, provided that when two hydroxyl groups are present, they are not attached to the same carbon atom; and

wherein [Sol] is selected from;

(i) NR¹⁸R¹⁹ where R¹⁸ is selected from hydrogen and C_1-3 alkyl where the C_1-3 alkyl is optionally substituted by hydroxyl, amino or mono- or di-methylamino; and

R¹⁹ is selected from R¹⁸ and monocyclic and bicyclic saturated heterocylic rings containing from 4 to 8 ring members and containing a nitrogen ring member and optionally a second heteroatom ring member selected from N and O; and

wherein the monocyclic and bicyclic saturated heterocylic rings are optionally substituted by one or more substituents selected from C_1-4 alkyl, hydroxy, amino, mono-C_1-2-alkylamino and mono-C_1-2-alkylamino and optionally substituted 4 to 6 membered saturated heterocyclic rings containing a nitrogen ring member and optionally a second ring member selected from nitrogen and oxygen wherein the optional substituents for the 4 to 6 membered saturated heterocyclic rings are selected from hydroxyl and methyl; and

(ii) monocyclic and bicyclic saturated heterocylic rings containing from 4 to 8 ring members and containing a nitrogen ring member and optionally a second heteroatom ring member selected from N and O; and

wherein the monocyclic and bicyclic saturated heterocylic rings are optionally substituted by one or more substituents selected from C_1-4 alkyl, hydroxy, —

OP(═

O)(OH)₂, amino, amino-C_1-4alkanoyloxy, mono-C_1-2-alkylamino and mono-C_1-2-alkylamino and optionally substituted 4 to 6 membered saturated heterocyclic rings containing a nitrogen ring member and optionally a second ring member selected from nitrogen and oxygen wherein the optional substituents for the 4 to 6 membered saturated heterocyclic rings are selected from hydroxyl and methyl.

16. A compound according to claim 15 wherein [Sol] is

(i) NR¹⁸R¹⁹ where R¹⁸ is selected from hydrogen and C_1-3 alkyl where the C_1-3 alkyl is optionally substituted by hydroxyl, amino or mono- or di-methylamino;

and R¹⁹ is selected from R¹⁸ and monocyclic and bicyclic saturated heterocylic rings containing from 4 to 8 ring members and containing a nitrogen ring member and optionally a second heteroatom ring member selected from N and O; and

wherein the monocyclic and bicyclic saturated heterocylic rings are optionally substituted by one or more substituents selected from C_1-4 alkyl, hydroxy, amino, mono-C_1-2-alkylamino and mono-C_1-2-alkylamino and optionally substituted 4 to 6 membered saturated heterocyclic rings containing a nitrogen ring member and optionally a second ring member selected from nitrogen and oxygen wherein the optional substituents for the 4 to 6 membered saturated heterocyclic rings are selected from hydroxyl and methyl; and

(ii) monocyclic and bicyclic saturated heterocylic rings containing from 4 to 8 ring members and containing a nitrogen ring member and optionally a second heteroatom ring member selected from N and O; and

wherein the monocyclic and bicyclic saturated heterocylic rings are optionally substituted by one or more substituents selected from C_1-4 alkyl, hydroxy, amino, mono-C_1-2-alkylamino and mono-C_1-2-alkylamino and optionally substituted 4 to 6 membered saturated heterocyclic rings containing a nitrogen ring member and optionally a second ring member selected from nitrogen and oxygen wherein the optional substituents for the 4 to 6 membered saturated heterocyclic rings are selected from hydroxyl and methyl.

17. A compound according to claim 1 selected from:

[2-(2,6-Difluoro-phenyl)-pyridin-4-yl]-[5-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl]-methanone;

[2-(2-Fluoro-6-methoxy-phenyl)-pyridin-4-yl]-[6-(4-methyl-piperazin-1-yl)-1H-benzoimidazol-2-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(2-fluoro-6-methoxy-phenyl)-pyridin-4-yl]-methanone;

(6′

-Fluoro-2′

-methoxy-biphenyl-3-yl)-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

1H-Imidazol-2-yl)-[3-(2-methyl-thiazol-4-yl)-phenyl]methanone;

(1H-Imidazol-2-yl)-(2-phenyl-pyridin-4-yl)-methanone;

(1H-Imidazol-2-yl)-[3-(2H-pyrazol-3-yl)-phenyl]-methanone;

(1H-Imidazol-2-yl)-(3-thiophen-3-yl-phenyl)-methanone;

[2-(4-Hydroxymethyl-phenyl)-pyridin-4-yl]-(1H-imidazol-2-yl)-methanone;

(1H-Imidazol-2-yl)-[2-(3-methoxy-phenyl)-pyridin-4-yl]-methanone;

(3-Chloro-5-thiophen-3-yl-phenyl)-(1H-imidazol-2-yl)-methanone;

(3′

-Amino-biphenyl-3-yl)-(1H-imidazol-2-yl)-methanone;

(3-Chloro-5-thiazol-4-yl-phenyl)-(1H-imidazol-2-yl)-methanone;

(3,5-Di-thiophen-3-yl-phenyl)-(1H-imidazol-2-yl)-methanone;

(1H-Imidazol-2-yl)-[3-(1-methyl-1H-pyrazol-3-yl)-5-thiophen-3-yl-phenyl]-methanone;

[2-(2,3-Difluoro-6-methoxy-phenyl)-pyridin-4-yl]-(1H-imidazol-2-yl)-methanone;

[2-(2,3-Difluoro-6-methoxy-phenyl)-pyridin-4-yl]-(5-dimethylaminomethyl-1H-benzoimidazol-2-yl)-methanone;

[2-(3,5-Dimethyl-isoxazol-4-yl)-pyridin-4-yl]-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

(5-Morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-(2-phenyl-pyridin-4-yl)-methanone;

[2-(2,6-Difluoro-phenyl)-pyridin-4-yl]-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

[2-(2,6-Difluoro-phenyl)-pyridin-4-yl]-(1H-imidazol-2-yl)-methanone;

[2-(4-Hydroxymethyl-phenyl)-pyridin-4-yl]-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

[2-(2-Fluoro-6-methoxy-phenyl)-pyridin-4-yl]-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

[2-(2,3-Difluoro-6-methoxy-phenyl)-pyridin-4-yl]-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

[2-(2-Methoxy-phenyl)-pyridin-4-yl]-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-methanone;

[4-(4-Dimethylamino-piperidin-1-ylmethyl)-1H-imidazol-2-yl]-[2-(2-fluoro-6-methoxy-phenyl)-pyridin-4-yl]-methanone;

(6-Chloro-2′

-methoxy-biphenyl-3-yl)-(5-dimethylaminomethyl-1H-benzoimidazol-2-yl)-methanone;

[2-(2-Fluoro-6-methoxy-phenyl)-1-oxy-pyridin-4-yl]-[5-(4-oxy-morpholin-4-ylmethyl)-1H-benzoimidazol-2-yl]-methanone;

(4-Dimethylaminomethyl-1H-benzoimidazol-2-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone (formate salt);

[2-(2,3-Difluoro-6-methoxy-phenyl)-pyridin-4-yl]-(4-dimethylaminomethyl-1H-benzoimidazol-2-yl)-methanone (hydrochloride salt);

(4-Hydroxy-1H-benzoimidazol-2-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone (methanesulfonate salt);

(2-Isoquinolin-4-yl-pyridin-4-yl)-[4-(1-methylamino-ethyl)-1H-benzoimidazol-2-yl]-methanone (trifluoroacetate salt);

(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-(5′

-ethylaminomethyl-[2,3′

]bipyridinyl-4-yl)-methanone (formate salt);

[5-(2-Dimethylamino-ethoxy)-1H-benzoimidazol-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

(6-Dimethylaminomethyl-1H-benzoimidazol-2-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

2-(2-Isoquinolin-4-yl-pyridine-4-carbonyl)-3H-benzoimidazole-5-carboxylic acid piperidin-4-ylamide (formate salt);

(2-Isoquinolin-4-yl-pyridin-4-yl)-[5-(4-methyl-piperazin-1-ylmethyl)-1H-benzoimidazol-2-yl]methanone (formate salt);

(2-Isoquinolin-4-yl-pyridin-4-yl)-[6-(piperazine-1-carbonyl)-1H-benzoimidazol-2-yl]-methanone (formate salt);

5-[5-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2′

-methoxy-biphenyl-2-carbonitrile (trifluoroacteate salt);

[5-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone (hydrochloride salt);

(2-Isoquinolin-4-yl-pyridin-4-yl)-[5-(4-methyl-piperazin-1-yl)-1H-benzoimidazol-2-yl)-methanone;

(2-Isoquinolin-4-yl-pyridin-4-yl)-(5-piperazin-1-yl-1H-benzoimidazol-2-yl)-methanone;

[5-(3-Amino-pyrrolidin-1-yl)-1H-benzoimidazol-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

(5-[1,4]Diazepan-1-yl-1H-benzoimidazol-2-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

(5,7-Difluoro-1H-benzoimidazol-2-yl)-(5′

-ethylaminomethyl-[2,3′

]bipyridinyl-4-yl)-methanone (hydrochloride salt);

(5,7-Difluoro-1H-benzoimidazol-2-yl)-(5′

-ethylaminomethyl-4′

-methyl-[2,3′

]bipyridinyl-4-yl)-methanone (hydrochloride salt);

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(5′

-ethylaminomethyl-[2,3′

]bipyridinyl-4-yl)-methanone (formate salt);

(2-Isoquinolin-4-yl-pyridin-4-yl)-[6-(4-methyl-piperazine-1-carbonyl)-1H-benzoimidazol-2-yl]methanone;

[5-(2,3-Dihydroxy-propoxy)-1H-benzoimidazol-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

2-(2-Isoquinolin-4-yl-pyridine-4-carbonyl)-3H-benzoimidazole-5-carboxylic acid methyl-piperidin-4-yl amide;

2-(2-Isoquinolin-4-yl-pyridine-4-carbonyl)-3H-benzoimidazole-5-carboxylic acid (1-methyl-piperidin-4-yl)-amide;

4-(5,6-Dimethoxy-1H-benzoimidazole-2-carbonyl)-2-(5-ethylaminomethyl-pyridin-3-yl)-benzonitrile;

[2-(2,3-Difluoro-6-methoxy-phenyl)-pyridin-4-yl]-[5-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]methanone;

[5-(4-Isopropyl-piperazin-1-yl)-1H-benzoimidazol-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

4-{4-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-4′

-methyl[2,3′

]bipyridinyl-6′

-yl}piperazine-1-carboxylic acid tert-butyl ester;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(4′

-methyl-6′

-piperazin-1-yl-[2,3′

]bipyridinyl-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(7-methyl-1H-indol-3-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(5-methyl-1H-pyrazol-4-yl)-pyridin-4-yl]methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(4′

-methyl-[2,3′

]bipyridinyl-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(1H-indol-3-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(1H-indol-4-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-pyrazolo[1,5-a]pyridin-3-yl-pyridin-4-yl)-methanone (methaneulfonate salt);

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(1H-pyrrolo[2,3-b]pyridin-5-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(1H-pyrrolo[3,2-b]pyridin-6-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-quinolin-3-yl-pyridin-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-naphthalen-1-yl-pyridin-4-yl)-methanone;

[2,4′

]Bipyridinyl-4-yl-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone;

[2,3′

]Bipyridinyl-4-yl-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(4′

-methoxy-[2,3′

]bipyridinyl-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(6′

-fluoro-4′

-methyl-[2,3′

]bipyridinyl-4-yl)-methanone;

2-{4-[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-pyridin-2-yl]-N-methyl-benzenesulfonamide;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(1,5-dimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(4-isopropyl-pyrimidin-5-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(2,4-dimethyl-thiazol-5-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(2-methyl-2H-pyrazol-3-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(5-fluoro-2-methoxy-phenyl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(4-piperidin-1-yl-phenyl)-pyridin-4-yl]-methanone (trifluoroacetate salt);

[2-(2,3-Dihydro-benzofuran-7-yl)-pyridin-4-yl]-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone (hydrochloride salt);

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone (formate salt);

(5′

-Amino-[2,3′

]bipyridinyl-4-yl)-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone (formate salt);

[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-pyridin-4-yl]-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-7-fluoro-1H-benzoimidazol-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone (trifluoroacetate salt);

[2-(4-Dimethylamino-piperidin-1-yl)-9H-purin-8-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

(2-[1,4]-Diazepan-1-yl-9H-purin-8-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

4-[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2-isoquinolin-4-yl-benzonitrile;

4-[5-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2-(3,5-dimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2-pyridin-3-yl-benzonitrile;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzonitrile;

446-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzonitrile;

446-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2-[1,6]naphthyridin-8-yl-benzonitrile;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-[1,6]naphthyridin-8-yl-benzonitrile;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(3,5-dimethyl-1H-pyrazol-4-yl)-benzonitrile;

[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-[2-(2,3-difloro-6-methoxy-phenyl)-pyridin-4-yl]-methanone;

[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(5-methyl-imidazol-1-yl)-pyridin-4-yl]-methanone (hydrochloride salt);

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(4-methyl-imidazol-1-yl)-pyridin-4-yl]-methanone (hydrochloride salt);

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(2-methyl-benzoimidazol-1-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(2,5-dimethyl-imidazol-1-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[2-(2,4-dimethyl-imidazol-1-yl)-pyridin-4-yl]-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-imidazo[4,5-c]pyridin-3-yl-pyridin-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-imidazo[4,5-c]pyridin-1-yl-pyridin-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-imidazo[4,5-b]pyridin-3-yl-pyridin-4-yl)-methanone;

[6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(2-imidazo[4,5-b]pyridin-1-yl-pyridin-4-yl)-methanone;

(2-Benzoimidazol-1-yl-pyridin-4-yl)-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone;

[5-(2,3-Difluoro-6-methoxy-phenyl)-pyridin-3-yl]-(5-dimethylaminomethyl-1H-benzoimidazol-2-yl)-methanone;

[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-[2-(2,3-difloro-6-methoxy-phenyl)-pyridin-4-yl]-methanone;

(5-[1,4]Diazepan-1-yl-3H-imidazo[4,5-b]pyridine-2-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

(2-Isoquinolin-4-yl-pyridin-4-yl)-5-piperazin-1-yl-3H-imidazo[4,5-b]pyridin-2-yl)-methanone;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-isoquinolin-4-yl-benzonitrile;

2-Isoquinolin-4-yl-4-(5-piperazin-1-yl-3H-imidazo[4,5-b]pyridine-2-carbonyl)-benzonitrile;

[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-yl]-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-benzonitrile;

[2-(3,5-Dimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-(5-piperazin-1-yl-3H-imidazo[4,5-b]pyridine-2-yl)-methanone;

(5-[1,4]Diazepan-1-yl-3H-imidazo[4,5-N-pyridin-2-yl)₄₂-(3,5-dimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

(5-[1,4]Diazepan-1-yl-3H-imidazo[4,5-N-pyridin-2-yl)₄₂-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

[5-(3-Amino-pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

2-(3-Methyl-isoquinolin-4-yl)-4-[5-(piperazine-1-carbonyl)-1H-benzoimidazole-2-carbonyl]-benzonitrile;

5-[5-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazole-2-carbonyl]-2-methoxy-biphenyl-2-carboxylic acid amide;

4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(2-methyl-imidazo[1,2-a]pyridin-3-yl)-benzonitrile;

2-(3,5-Dimethyl-1H-pyrazol-4-yl)-4-[6-(piperazine-1-carbonyl)-1H-benzoimidazole-2-carbonyl]-benzonitrile;

(2-Isoquinolin-4-yl-pyridin-4-yl)-[5-(piperazine-1-carbonyl)-3H-imidazo[4,5-b]pyridin-2-yl]-methanone;

4-(5-[1,4′

]Bipiperidinyl-1′

-yl-3H-imidazo[4,5-b]pyridine-2-carbonyl)-2-(3,5-dimethyl-1H-pyrazol-4-yl)-benzonitrile;

2-Isoquinolin-4-yl-4-[6-(piperazine-1-carbonyl)-1H-benzoimidazole-2-carbonyl]-benzonitrile;

4-(6-Chloro-1H-benzoimidazole-2-carbonyl)-2-[1,6]naphthyridin-8-yl-benzonitrile;

(2-Isoquinolin-4-yl-pyridin-4-yl)-[6-(piperazine-1-sulfonyl)-1H-benzoimidazol-2-yl]-methanone;

[6-(piperazine-1-carbonyl)-1H-benzoimidazol-2-yl]-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone;

4-[6-(piperazine-1-carbonyl)-1H-benzoimidazole-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

2-(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)-4-[6-(piperazine-1-carbonyl)-1H-benzoimidazole-2-carbonyl]-benzonitrile;

2-(4-Cyano-3-isoquinolin-4-yl-benzoyl)-3H-benzoimidazole-5-sulfonic acid (2-amino-ethyl)-methyl-amide;

2-(3,5-Dimethyl-isoxazol-4-yl)-4-[6-(piperazine-1-carbonyl)-1H-benzoimidazole-2-carbonyl]-benzonitrile;

6-(4-Dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-[3-(3,5-dimethyl-1H-pyrazol-4-yl)-4-fluoro-phenyl]methanone;

4-(5-piperazin-1-yl-3H-imidazo[4,5-b]pyridine-2-carbonyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

(5-[1,4′

]Bipiperidinyl-1′

-yl-3H-imidazo[4,5-b]pyridin-2-yl)-(2-isoquinolin-4-yl-pyridin-4-yl)-methanone;

4-[2-(2-Isoquinolin-4-yl-pyridine-4-carbonyl)-3H-imidazo[4,5-b]pyridin-6-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester;

(2-Isoquinolin-4-yl-pyridin-4-yl)-[6-(piperazine-1-carbonyl)-1H-benzoimidazol-2-yl]-methanone;

4-[2-(2-Isoquinolin-4-yl-pyridine-4-carbonyl)-3H-imidazo[4,5-b]pyridin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester;

4-[2-(4-Cyano-3-isoquinolin-4-yl-benzoyl)-3H-imidazo[4,5-b]pyridin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester;

4-[5-(pyrrolidin-3-yloxy)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzamide;

4-[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-N,N-dimethyl-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzamide;

[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(3-isoquinolin-4-yl-4-methoxy-phenyl)-methanone;

[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(4-hydroxy-3-isoquinolin-4-yl-phenyl)-methanone;

4-[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-benzonitrile;

4-[5-(4-hydroxy-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzonitrile;

(S)-2-amino-3-methyl-butyric-acid-1-{2-[4-cyano-3-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzoyl]-3H-imidazo[4,5-b]pyridin-5-yl}-piperidin-4-yl ester;

phosphoric-acid-mono-(1-{2-[4-cyano-3-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzoyl]-3H-imidazo[4,5-b]pyridin-5-yl]-piperidin-4-yl)ester;

4-[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(5-methoxy-1H-pyrrolo[2,3-c]pyridin-4-yl)-benzonitrile;

4-[5-(pyrrolidin-3-yloxy)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzonitrile;

4-{5-[2-(4-methyl-piperazin-1-yl)-ethoxy]-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(3,6-diaza-bicyclo[3.2.0]hept-3-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(2,6-diaza-spiro[3.3]hept-2-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(2,6-diaza-spiro[3.3]hept-2-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-benzonitrile;

4-[5-(3,3-dimethyl-2-oxo-piperazin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(pyrrolidin-3-ylamino)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

4-[5-(3-amino-pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile; and

4-[5-(6-amino-3-aza-bicyclo[3.1.0]hex-3-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzonitrile;

and salts, solvates, tautomers and N-oxides thereof.

18. A pharmaceutical composition comprising a compound according to claim 1, or a salt, solvate, tautomer or N-oxide thereof, and a pharmaceutically acceptable carrier.