Heterocyclic compounds and uses thereof

• US 9,828,377 B2
• Filed: 04/24/2015
• Issued: 11/28/2017
• Est. Priority Date: 10/04/2013
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Castro, Alfredo C., Evans, Catherine A., Janardanannair, Somarajannair, Lescarbeau, Andre, Liu, Tao, Tremblay, Martin R.
• Primary Examiner(s): Bernhardt, Emily
• Application Number:
  US14/695,699
• Publication Number:
  US 20150225410A1
• Time in Patent Office: 949 Days
• Field of Search: None
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 containing three or more hetero 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 471/08 Bridged systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Provided herein are compounds of Formula (I″) or (A″), pharmaceutical compositions comprising the compounds, and methods of use thereof. The compounds provided herein modulate kinase activity, including PI3 kinase activity, and are useful for treating diseases and conditions associated with kinase activity, including PI3 kinase activity.

Claims

1. A compound of Formula (I):

2. The compound of claim 1, wherein

R¹ is branched alkyl, 6-membered aryl, 5- or 6-membered heteroaryl, 5- or 6-membered cycloalkyl, or 5- to 6-membered heterocycloalkyl,

3. The compound of claim 2, wherein

R¹ is:

methyl,

4. The compound of claim 1, wherein R¹ is a 5- to 10-membered heteroaryl, which is optionally substituted.

5. The compound of claim 4, wherein R¹ is a 6-membered heteroaryl, which is optionally substituted.

6. The compound of claim 5, wherein R¹ is a pyridinyl or pyrimidinyl, each of which is optionally substituted.

7. The compound of claim 4, wherein R¹ is a 5-membered heteroaryl, which is optionally substituted.

8. The compound of claim 7, wherein R¹ is a thiazolyl, pyrazolyl, or imidazolyl, each of which is optionally substituted.

9. The compound of claim 4, wherein the heteroaryl is substituted with one or more alkyl.

10. The compound of claim 1, wherein B is aryl or cycloalkyl, each of which is optionally substituted.

11. The compound of claim 10, wherein B is aryl or 3- to 6-membered cycloalkyl, each of which is optionally substituted.

12. The compound of claim 11, wherein B is phenyl substituted with 0, 1, 2, or 3 occurrence(s) of R^Z, wherein each instance of R^Z is independently halo or alkyl.

13. The compound of claim 12, wherein B is unsubstituted phenyl.

14. The compound of claim 11, wherein B is

15. The compound of claim 1, wherein W^d is

16. The compound of claim 1, wherein W^d is

17. The compound of claim 1, wherein W^d is

18. The compound of claim 1, wherein W^d is

19. The compound of claim 1, wherein X is CH.

20. The compound of claim 1, wherein the compound is a compound of formula II, III, V, VI, VIII, IX, or XII:

21. The compound of claim 1, wherein the compound is the S-enantiomer having an enantiomeric purity greater than 75%.

22. A pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable excipient, diluent, or carrier.

23. The compound of claim 8, wherein R¹ is a pyrazolyl, which is optionally substituted.

24. The compound of claim 23, wherein R¹ is a pyrazolyl, and wherein the pyrazolyl is substituted with one or more alkyl.

25. The compound of claim 24, wherein R¹ is

26. The compound of claim 1, wherein the compound is a compound of formula III:

27. The compound of claim 26, wherein R¹ is 5- or 6-membered heteroaryl, which is optionally substituted.

28. The compound of claim 27, wherein R¹ is a pyrazolyl, which is optionally substituted.

29. The compound of claim 28, wherein R¹ is a pyrazolyl, and wherein the pyrazolyl is substituted with one or more alkyl.

30. The compound of claim 29, wherein R¹ is

31. The compound of claim 30, wherein R¹ is

32. The compound of claim 1, wherein the compound is a compound of formula VI:

33. The compound of claim 32, wherein R¹ is 5- or 6-membered heteroaryl, which is optionally substituted.

34. The compound of claim 33, wherein R¹ is a pyrazolyl, which is optionally substituted.

35. The compound of claim 34, wherein R¹ is a pyrazolyl, and wherein the pyrazolyl is substituted with one or more alkyl.

36. The compound of claim 1, wherein the compound is a compound of formula XIV:

37. The compound of claim 1, wherein the compound is a compound of formula XV:

38. The compound of claim 15, wherein W^d is

39. The compound of claim 1, which is

40. The compound of claim 1, which is:

41. A pharmaceutical composition comprising a compound of claim 40, and a pharmaceutically acceptable excipient, diluent, or carrier.

42. The compound of claim 1, which is:

43. A pharmaceutical composition comprising a compound of claim 42, and a pharmaceutically acceptable excipient, diluent, or carrier.