HETEROCYCLIC COMPOUNDS AND USES THEREOF

• US 20150225410A1
• Filed: 04/24/2015
• Published: 08/13/2015
• 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, TREMBLAY, Martin R., LIU, Tao
• Granted Patent: US 9,828,377 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Claims

1. A compound of Formula (I″

) or Formula (A″

);

5. The compound of any one of claims 1-4, wherein

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

6. The compound of claim 5, wherein

R¹ is:

methyl,

7. The compound of any one of claims 1-4, wherein R¹ is a 5- to 10-membered heteroaryl.

8. The compound of claim 7, wherein R¹ is a 6-membered heteroaryl.

9. The compound of claim 8, wherein R¹ is a pyridinyl or pyrimidinyl.

10. The compound of claim 7, wherein R¹ is a 5-membered heteroaryl.

11. The compound of claim 10, wherein R¹ is a thiazolyl, pyrazolyl, or imidazolyl.

12. The compound of any one of claims 7-11, wherein the heteroaryl is substituted with one or more alkyl.

13. The compound of any one of claims 1-12, wherein B is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl.

14. The compound of claim 13, wherein B is aryl or 3- to 6-membered cycloalkyl.

15. The compound of claim 14, 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.

16. The compound of claim 15, wherein B is unsubstituted phenyl.

17. The compound of claim 14, wherein B is

18. The compound of any one of claims 1-17, wherein W^d is heteroaryl.

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

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

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

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

23. The compound of any one of claims 1-22, wherein X is CH.

24. The compound of any one of claims 1-22, wherein X is N.

34. The compound of claim 1, wherein the compound is in an (S)-stereochemical configuration.

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

37. A pharmaceutical composition comprising a compound of any one of claims 1-36, and a pharmaceutically acceptable excipient, diluent, or carrier.

38. A method of inhibiting a PI3 kinase, comprising contacting the PI3 kinase with an effective amount of a compound of any one of claims 1-36 or a composition of claim 37.

39. The method of claim 38, wherein the PI3 kinase is present in a cell.

40. The method of claim 38 or 39, wherein the inhibition takes place in a subject suffering from a PI3K mediated disorder.

41. A method of treating or preventing a PI3K mediated disorder in a subject, comprising administering a therapeutically effective amount of a compound of any one of claims 1-36 or a composition of claim 37 to said subject.

42. The method of claim 40 or 41, wherein the PI3K mediated disorder is a PI3K-γ

mediated disorder.

43. The method of claim 40 or 41, wherein the PI3K mediated disorder is cancer, an inflammatory disease, or an auto-immune disease.

44. The method of claim 43, wherein the cancer is a hematological cancer.

45. The method of claim 43, wherein the cancer is a solid tumor.

46. The method of any one of claims 40-45 wherein the subject is a human.

2. A compound of Formula (I′

) or Formula (A′

);

3. A compound of Formula (I) or Formula (A):

4. The compound of claim 3, wherein the compound is a compound of Formula (I):

25. The compound of claim 4, wherein the compound is a compound of formula II, III, IV, V, VI, VII, VIII, IX, X, XI, or XII:

26. The compound of claim 3, wherein the compound is a compound of Formula (A):

27. The compound of claim 26, wherein R¹ is alkyl or heteroaryl.

28. The compound of claim 27, wherein R¹ is heteroaryl.

29. The compound of claim 27, wherein R¹ is alkyl.

30. The compound of any one of claims 26-29, wherein B is phenyl.

31. The compound of any one of claims 26-30, wherein X is CH.

32. The compound of any one of claims 26-30, wherein X is N.

33. The compound of any one of claims 26-32, wherein W^d is

36. A compound in Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, or Table 14, or a pharmaceutically acceptable form thereof.