Heterocyclic compounds and uses thereof

• US 8,969,363 B2
• Filed: 07/18/2012
• Issued: 03/03/2015
• Est. Priority Date: 07/19/2011
• 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, Snyder, Daniel A., Tremblay, Martin R., Ren, Pingda, Liu, Yi, Li, Liansheng, Chan, Katrina
• Primary Examiner(s): Ward, Paul V.
• Application Number:
  US13/552,460
• Publication Number:
  US 20130029982A1
• Time in Patent Office: 958 Days
• Field of Search: 544/283, 544/278, 544/279, 514/266.1, 514/264.11
• US Class Current: 514/264.11
• 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 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 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07D 513/04 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):

2. The compound of claim 1, wherein Cy is aryl substituted with 0-1 occurrences of R³ and 0-3 occurrences of R₅.

3. The compound of claim 2, wherein Cy is phenyl substituted with 1 occurrence of R³ and 0 occurrences of R₅.

4. The compound of claim 3, wherein the compound of Formula (I) has a structure of Formula (IIa) or (IIb):

5. The compound of claim 4, wherein the compound of Formula (I) has a structure of Formula (IIIa) or (IIIb):

6. The compound of claim 5, wherein the compound of Formula (I) has a structure of Formula (IIIb-1):

7. The compound of claim 1, wherein Cy is heteroaryl substituted with 0-1 occurrences of R³ and 0-3 occurrences of R₅.

8. The compound of claim 7, wherein Cy is 5-membered heteroaryl substituted with 0-1 occurrences of R³ and 0-3 occurrences of R⁵.

9. The compound of claim 8, wherein Cy is isothiazolyl substituted with 0-1 occurrences of R³ and 0 occurrence of R⁵.

10. The compound of claim 9, wherein the compound of Formula (I) has the structure of Formula (IVa) or Formula (IVb):

11. The compound of claim 10, wherein the compound of Formula (IVa) or Formula (IVb) has the structure of Formula (Va) or Formula (Vb):

12. The compound of claim 11, wherein the compound of Formula (I) has a structure of Formula (Va-1):

13. The compound of claim 8, wherein Cy is thiophenyl substituted with 0-1 occurrences of R³ and 0 occurrence of R⁵.

14. The compound of claim 13, wherein the compound of Formula (I) has the structure of Formula (VIa) or Formula (VIb):

15. The compound of claim 14, wherein the compound of Formula (VIa) or Formula (VIb) has the structure of Formula (VIIa) or (VIIb):

16. The compound of claim 14, wherein the compound of Formula (VIa) or Formula (VIb) has the structure of Formula (VIIIa) or Formula (VIIIb):

17. The compound of claim 16, wherein the compound of Formula (VIIa) or Formula (VIIb) has the structure of Formula (IXa) or Formula (IXb):

18. The compound of claim 17, wherein the compound of Formula (I) has a structure of Formula (IXa-1):

19. The compound of claim 1, wherein each R⁵ is independently selected from CH₃, OCH₃, and halo.

20. The compound of claim 1. wherein R³ is unsubstituted alkyl or R³ is selected from cycloalkyl, halo, aryl, and heteroaryl.

21. The compound of claim 20, wherein R³ is selected from methyl, chloro, and pyrazolo.

22. The compound of claim 1, wherein B is aryl substituted with 0-3 occurrences of R².

23. The compound of claim 22, wherein B is phenyl substituted with 0-3 occurrences of R².

24. The compound of claim 23, wherein B is unsubstituted phenyl.

25. The compound of claim 23, wherein B is phenyl substituted with 1 occurrence of R².

26. The compound of claim 1, wherein R² is halo or alkyl.

27. The compound of claim 1, wherein B is cycloalkyl.

28. The compound of claim 1, wherein B is heterocyclyl.

29. The compound of claim 1, wherein Y is absent, —

O—

, —

N(R⁹)—

, or —

S(═

O)₂—

.

30. The compound of claim 1, wherein X-Y is —

CH₂—

N(CH₃)—

.

31. The compound of claim 1, wherein X-Y is (S)—

CH(CH₃)—

NH—

.

32. The compound of claim 1, wherein X-Y is (R)—

CH(CH₃)—

NH—

.

33. The compound of claim 1, wherein X₁ is N.

34. The compound of claim 1, wherein R¹⁰, R¹¹, R¹², R¹³ are independently selected from hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, and hydroxyl.

35. The compound of claim 34, wherein R¹⁰, R¹¹, R¹², and R¹³ are independently selected from hydrogen, amino, and chloro.

36. The compound of claim 35, wherein R¹⁰ is selected from amino and chloro.

37. The compound of claim 1. wherein R⁸ is hydrogen.

38. The compound of claim 1, wherein the compound is

39. The compound of claim 1, wherein the compounds is

40. The compound of claim 1, wherein the compounds is

41. The compound of claim 1, wherein the compounds is

42. The compound of claim 1, wherein the compounds is

43. The compound of claim 1, wherein the compounds is

47. The compound of claim 39, wherein the compound is

48. The compound of claim 39, wherein the compound is

49. A pharmaceutical composition comprising a compound according to claim 1 and one or more pharmaceutically acceptable excipients.

50. A pharmaceutical composition comprising a compound according to claim 38 and one or more pharmaceutically acceptable excipients.

51. A pharmaceutical composition comprising a compound according to claim 39 and one or more pharmaceutically acceptable excipients.

55. A pharmaceutical composition comprising a compound according to claim 47 and one or more pharmaceutically acceptable excipients.

56. A pharmaceutical composition comprising a compound according to claim 48 and one or more pharmaceutically acceptable excipients.

44. A compound selected from

52. A pharmaceutical composition comprising a compound according to claim 44 and one or more pharmaceutically acceptable excipients.

45. A compound selected from

46. The compound of claim 45, wherein the compound is

53. A pharmaceutical composition comprising a compound according to claim 45 and one or more pharmaceutically acceptable excipients.

54. A pharmaceutical composition comprising a compound according to claim 46 and one or more pharmaceutically acceptable excipients.