Amide derivatives as C-KIT modulators

• US 20050165074A1
• Filed: 11/15/2004
• Published: 07/28/2005
• Est. Priority Date: 11/13/2003
• Status: Abandoned Application

• Current Assignee: Ambit Biosciences Corporation (Daiichi Sankyo Company Limited)
• Original Assignee: Ambit Biosciences Corporation (Daiichi Sankyo Company Limited)
• Inventors: Patel, Hitesh K., Lockhart, David J., Lai, Andiliy G., Milanov, Zdravko V., Mehta, Shamal A., Grotzfeld, Robert M.
• Application Number:
  US10/990,007
• Publication Number:
  US 20050165074A1
• Time in Patent Office: Days
• US Class Current: 514/378
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/08 Bronchodilators
• 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 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/40 Acylated on said nitrogen atom
• CPC Class Codes: C07D 261/08 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 261/14 Nitrogen atoms
• CPC Class Codes: C07D 261/18 Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
• CPC Class Codes: C07D 277/46 by carboxylic acids, or sulfur or nitrogen analogues thereof
• CPC Class Codes: C07D 277/82 Nitrogen atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• 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 471/06 : Peri-condensed systems
• 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
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides methods and compositions for treating conditions mediated by c-kit wherein derivatives of amide compounds are employed. The invention also provides methods of using the compounds and/or compositions in the treatment of a variety of diseases and unwanted conditions in subjects.

Claims

1. A method of modulating c-kit kinase, said method comprising administering an effective amount of a compound corresponding to Formula (IA):

2. The method of claim 1, wherein said compound corresponds to Formula (IB):

3. The method of claim 2, wherein said compound corresponds to Formula (I):

4. The method of claim 3, wherein said compound corresponds to Formula (II):

5. The method of claim 4, wherein said compound corresponds to Formula (III):

6. The method of claim 5, wherein said compound corresponds to Formula (IV):

7. The method of claim 6, wherein the compound is:

8. The method of claim 5, wherein said compound corresponds to Formula (V):

9. The method of claim 8, wherein said compound is selected from the group consisting of:

10. The method of claim 4, wherein said compound corresponds to Formula (VI):

11. The method of claim 10, wherein said compound corresponds to Formula (VII):

12. The method of claim 10, wherein said compound corresponds to Formula (VIII):

13. The method of claim 12, wherein said compound is selected from the group consisting of:

14. The method of claim 5, wherein said compound corresponds to Formula (IX):

15. The method of claim 14, wherein T of said compound corresponds to Formula (X):

16. The method of claim 15, wherein said compound corresponds to Formula (XI):

17. The method of claim 16, wherein L of said compound is a covalent bond, —

C(O)NH(substituted or unsubstituted alkylene), —

O(substituted or unsubstituted alkylene)-, —

C(O)NH—

, or —

NHC(O)(alkylene)-.

18. The method of claim 17, wherein B of said compound is a substituted or unsubstituted five-membered heteroarylene.

19. The method of claim 18, wherein said compound is selected from the group consisting of:

20. The method of claim 17, wherein B of said compound is a substituted or unsubstituted 6-membered arylene or heteroarylene.

21. The method of claim 20, wherein said compound is selected from the group consisting of:

22. The method of claim 20, wherein said compound is selected from the group consisting of:

23. The method of claim 14, wherein T of said compound is a tricyclic, substituted or unsubstituted aryl, heterocyclyl, or heteroaryl.

24. The method of claim 23, wherein said compound is selected from the group consisting of:

25. The method of claim 5, wherein said compound corresponds to Formula (XII):

26. The method of claim 25, wherein said compound corresponds to Formula (XIII):

27. The method of claim 26, wherein L of said compound is a covalent bond, —

C(O)NH—

, or —

O(substituted or unsubstituted alkylene)-.

28. The method of claim 27, wherein

29. The method of claim 28, wherein said compound is selected from the group consisting of:

30. The method of claim 5, wherein said compound corresponds to Formula (XIV):

31. The method of claim 30, wherein said compound corresponds to Formula (XV):

32. The method of claim 31, wherein said compound is selected from the group consisting of:

33. The method of claim 31, wherein said compound corresponds to Formula (XVI):

34. The method of claim 33, wherein said compound is selected from the group consisting of:

35. The method of claim 31, wherein said compound corresponds to Formula (XVII):

36. The method of claim 35, wherein said compound is selected from the group consisting of:

37. The method of claim 31, wherein said compound corresponds to Formula (XVIII):

38. The method of claim 37, wherein said compound is selected from the group consisting of:

39. The method of claim 31, wherein said compound corresponds to Formula (XIX):

40. The method of claim 39, wherein said compound is selected from the group consisting of:

41. The method of claim 31, wherein said compound corresponds to Formula (XX):

42. The method of claim 41, wherein said compound is selected from the group consisting of:

43. The method of claim 31, wherein said compound corresponds to Formula (XXI):

44. The method of claim 43, wherein L of said compound is —

NHC(O)—

, —

NHC(O)(substituted or unsubstituted alkylene)-, —

C(O)NH(substituted or unsubstituted alkylene), —

C(O)NH(substituted or unsubstituted alkenylene), or —

NHC(O)(substituted or unsubstituted alkenylene)-.

45. The method of claim 44, wherein said compound is selected from the group consisting of:

46. The method of claim 43, wherein L of said compound is —

O—

or —

O(substituted or unsubstituted alkylene)-.

47. The method of claim 46, wherein said compound is selected from the group consisting of:

48. The method of claim 43, wherein L of said compound is -(substituted or unsubstituted alkylene)- or —

NHC(O)(alkylene)S(alkylene)C(O)NH—

.

49. The method of claim 48, wherein said compound is selected from the group consisting of:

50. The method of claim 14, wherein said compound corresponds to Formula (XXII):

51. The method of claim 50, wherein said compound corresponds to Formula (XXIII):

52. The method of claim 51, wherein L₁ of said compound is a bond, —

O(substituted or unsubstituted alkylene)-, -(substituted or unsubstituted alkylene)-, or —

S—

; and

L of said compound is a covalent bond, —

C(O)NH—

, —

C(O)NH(substituted or unsubstituted alkylene), or —

NHC(O)(substituted or unsubstituted alkylene)-.

53. The method of claim 52, wherein V of said compound is substituted or unsubstituted 5-membered heteroarylene.

54. The method of claim 53, wherein said compound is selected from the group consisting of:

55. The method of claim 51, wherein said compound corresponds to Formula (XXIV):

56. The method of claim 55, wherein U of said compound is substituted or unsubstituted pyrimidinyl or pyridinyl.

57. The method of claim 56, wherein said compound is selected from the group consisting of:

58. The method of claim 55, wherein U of said compound is substituted or unsubstituted phenyl.

59. The method of claim 58, wherein said compound is selected from the group consisting of:

60. The method of claim 51, wherein said compound is selected from the group consisting of:

61. The method of claim 14, wherein said compound corresponds to Formula (XXV):

62. The method of claim 61, wherein said compound is selected from the group consisting of:

63. The method of claim 1, wherein said compound is

64. The method of claim 1, wherein said compound is selected from the group consisting of:

65. A method of treating a c-kit mediated disease, said method comprising administering a therapeutically effective amount of a compound corresponding to Formula (IA):