CDC7 inhibitors

Patent metadata

Field	Value
Publication number	US-9156824-B2
Application number	US-201414200141-A
Country	US
Kind code	B2
Filing date	Mar 7, 2014
Priority date	Mar 14, 2013
Publication date	Oct 13, 2015
Grant date	Oct 13, 2015

Abstract

The present invention provides isoindolinone compounds, or a pharmaceutically acceptable salt thereof, that inhibit CDC7 and, therefore may be useful in treating cancer.

First claim

We claim:

1. A compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, or a pharmaceutically acceptable salt or hydrate thereof.

2. The compound according to claim 1 which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one.

3. The compound according to claim 1 , which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 2, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 3 , which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 2.

5. The compound according to claim 1 , which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 1, or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 5 , which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 1.

7. The compound according to claim 1 which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, or hydrate thereof.

8. The compound according to claim 7 which is a hydrate in a crystalline form characterized by a X-ray powder diffraction pattern having characteristic peaks, in 2θ±0.2, occurring at 22.27 and one or more of 13.46, 16.54, 16.66, 18.10 and 23.13.

9. A pharmaceutical composition comprising a compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier, diluent, or excipient.

10. The pharmaceutical composition according to claim 9 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one.

11. The pharmaceutical composition according to claim 9 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 2, or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition according to claim 11 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 2.

13. The pharmaceutical composition according to claim 9 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 1, or a pharmaceutically acceptable salt thereof.

14. The pharmaceutical composition according to claim 13 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 1.

15. The pharmaceutical composition according to claim 9 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, or hydrate thereof.

16. The pharmaceutical composition according to claim 15 comprising the compound which is a hydrate in a crystalline form characterized by a X-ray powder diffraction pattern having characteristic peaks, in 2θ±0.2, occurring at 22.27 and one or more of 13.46, 16.54, 16.66, 18.10 and 23.13.

17. A method of treating a cancer wherein the cancer is selected from the group consisting of breast cancer, lung cancer, colorectal cancer, and leukemia, comprising administering to a patient in need thereof, an effective amount of a compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, or a pharmaceutically acceptable salt or hydrate thereof.

18. The method according to claim 17 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one.

19. The method according to claim 17 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 2, or a pharmaceutically acceptable salt thereof.

20. The method according to claim 19 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 2.

21. The method according to claim 17 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 1, or a pharmaceutically acceptable salt thereof.

22. The method according to claim 21 comprising the compound which is 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, isomer 1.

23. The method according to claim 17 comprising the compound 3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)isoindolin-1-one, or hydrate thereof.

24. The method according to claim 23 comprising the compound which is a hydrate in a crystalline form characterized by a X-ray powder diffraction pattern having characteristic peaks, in 2θ±0.2, occurring at 22.27 and one or more of 13.46, 16.54, 16.66, 18.10 and 23.13.

25. The method according to claim 17 , wherein the cancer is colorectal cancer.

26. The method according to claim 18 , wherein the cancer is colorectal cancer.

27. The method according to claim 19 , wherein the cancer is colorectal cancer.

28. The method according to claim 20 , wherein the cancer is colorectal cancer.

29. The method according to claim 21 , wherein the cancer is colorectal cancer.

30. The method according to claim 22 , wherein the cancer is colorectal cancer.

31. The method according to claim 23 , wherein the cancer is colorectal cancer.

32. The method according to claim 24 , wherein the cancer is colorectal cancer.

Assignees

• Lilly Co Eli

Inventors

• Dally Robert Dean
• Woods Timothy Andrew

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title