1H-pyrrolo [2,3-b] pyridine derivatives and their use as kinase inhibitors

1. A method for treating ovarian cancer, triple negative breast cancer, melanoma, neuroblastoma, or pancreatic cancer in a mammal subject in need thereof comprising administering to the mammal subject a therapeutically effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

each Z is independently (Alk) n -R n -(Alk) n -X, wherein:

each Alk is independently (C 1 to C 12 ) alkylene or (C 2 to C 12 ) alkenylene, each of which is optionally substituted;

each n is independently 0 or 1;

each R is independently optionally substituted arylene, optionally substituted heteroarylene, optionally substituted cycloalkylene, optionally substituted heterocycle, —O—,

—S—, —(C═O)—, —(C═S)—, —SO 2 —, —C(═O)O—, —C(═O)NR A —, —C(═S)NR A —, —SO 2 NR A —, —NR A C(═O)—, —NR A SO 2 —, or —NR A —, wherein R A is hydrogen, C 1 -C 6 alkyl, —C 1 -C 6 alkyl(cycloalkyl), C 1 -C 6 alkyl(C 1 -C 6 alkoxy), or C 1 -C 6 alkoxy; and

each X is independently halogen, —H, —OR A , —NR A R A , optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycle, CN, or C(halogen) a H b , where a is 1, 2, or 3, and b is (3-a);

Y is phenyl optionally substituted with C 1 to C 6 alkyl or halogen; optionally substituted, bicyclic or tricyclic aryl; optionally substituted heteroaryl; optionally substituted cycloalkyl; or optionally substituted heterocycle; and

R 1 is H or C 1 -C 6 alkyl.

2. The method according to claim 1 , wherein the cancer is ovarian cancer.

3. The method according to claim 1 , wherein the condition is cancer and the compound is administered in combination with radiotherapy or chemotherapy.

4. The method according to claim 1 , wherein R A is hydrogen or C 1 -C 6 alkyl.

5. The method according to claim 1 , wherein at least one Z is H, halogen, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nitrogen-containing heterocycle, C 1 to C 6 alkyl, or —OR A .

6. The method according to claim 5 , wherein one Z group is H, halogen, —OR A , or C 1 to C 6 alkyl, and the other Z group is optionally substituted aryl or optionally substituted nitrogen-containing heterocycle.

7. The method according to claim 6 , wherein the nitrogen-containing heterocycle is substituted with —NR A R A .

8. The method according to claim 1 , wherein at least one Z is (Alk) n -optionally substituted arylene-(Alk) n -optionally substituted heterocycle.

9. The method according to claim 1 , wherein R is H.

10. The method according to claim 1 , wherein Y is phenyl optionally substituted with C 1 to C 6 alkyl or halogen; or heteroaryl optionally substituted with C 1 to C 6 alkyl, —OR A , halogen, or C 1 to C 6 alkoxy.

11. The method according to claim 1 , wherein Y is pyridyl, pyrrolyl, phenyl; or phenyl substituted with methyl, bromine, or chlorine.

12. The method according to claim 1 , wherein the compound is of the formula (Ia):

or a pharmaceutically acceptable salt thereof, wherein:

Z 1 and Z 2 are independently (Alk) n -R n -(Alk) n -X.

13. The method according to claim 12 , wherein Z 1 is halogen, phenyl, —OR A , or C 1 to C 6 alkyl, and Z 2 is optionally substituted aryl or optionally substituted heterocycle.

14. The method according to claim 12 , wherein Z 2 is halogen, CF 3 , cyclopropyl, phenyl, —OR A , or C 1 to C 6 alkyl, and Z 1 is optionally substituted aryl or optionally substituted heterocycle.

15. The method according to claim 12 , wherein the optionally substituted heterocycle is an optionally substituted piperidine, optionally substituted piperazine, or optionally substituted morpholine.

16. The method according to claim 1 , wherein the compound is one of the compounds listed below, or a pharmaceutically acceptable salt thereof:

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (4-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-piperidin-1-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

N-{4-[(3R)-3-Aminopiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl}-1-benzyl-1H-pyrazole-4-carboxamide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-pyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-methylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-ethylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-hydroxy-pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-hydroxy-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-(3-dimethylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-bromo-4-[(R)-3-(cyclopentylmethyl-amino)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-isobutylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-bromo-4-[(R)-3-(2,2-dimethyl-propylamino)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-bromo-4-[(R)-3-(cyclopropylmethyl-amino)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(4-Chloro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(4-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

N-{4-[(3R)-3-aminopiperidin-1-yl]-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl}-1-benzyl-1H-pyrazole-4-carboxamide;

1-(4-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(4-Chloro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-pyrrolidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

N-{4-[(3R)-3-aminopiperidin-1-yl]-5-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-1-benzyl-1H-pyrazole-4-carboxamide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-piperidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(4-fluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-dimethylaminomethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(3-fluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-methylaminomethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-morpholin-4-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(3,3-difluoro-pyrrolidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-dimethylaminomethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3-fluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3,3-difluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-azetidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3,3-difluoro-azetidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(5-pyrrolidin-1-ylmethyl-thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(5-pyrrolidin-1-ylmethyl-thiophen-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[5-(3,3-difluoro-azetidin-1-ylmethyl)-thiophen-3-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(2-morpholin-4-yl-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3-dimethylamino-2,2-dimethyl-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3-morpholin-4-yl-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(1-methyl-piperidin-3-ylmethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(oxetan-3-yloxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((3R,4R)-3-amino-4-cyclopropyl-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(2-fluoro-4-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-pyrrolidin-1-yl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-(2-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-(2-Cyano-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-(1H-Pyrrol-2-ylmethyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(1-methyl-piperidin-3-yloxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(3-dimethylamino-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[1-(2-diethylamino-ethyl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;

1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(3-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(3-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(2-Chloro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(2-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;

1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide; and

1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide.

17. The method according to claim 1 , wherein the cancer is triple negative breast cancer.

18. The method according to claim 1 , wherein the mammal subject is a human subject.

19. The method according to claim 1 , wherein the cancer is neuroblastoma.