Amide derivatives as FLT-3 modulators

• US 20050171171A1
• Filed: 11/15/2004
• Published: 08/04/2005
• 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:
  US10/989,766
• Publication Number:
  US 20050171171A1
• 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 flt-3 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 flt-3 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 is selected from the group consisting of:

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

8. The method of claim 7, 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 said compound is selected from the group consisting of:

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

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

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

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

NHC(O)—

, —

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

NH—

, or —

O(substituted or unsubstituted alkylene)-.

19. The method of claim 18, wherein said compound corresponds to Formula (XII):

20. The method of claim 19, wherein B of said compound is a substituted or unsubstituted five-membered arylene or heteroarylene.

21. The method of claim 20, wherein said compound is:

22. The method of claim 20, wherein B is substituted or unsubstituted thiophenylene.

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

24. The method of claim 20, wherein B is substituted or unsubstituted imidazolylene.

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

26. The method of claim 20, wherein B is substituted or unsubstituted pyrrolylene.

27. The method of claim 26, wherein said compound is selected from the group consisting of:

28. The method of claim 19, wherein B of said compound is a substituted or unsubstituted 6-membered arylene or heteroarylene.

29. The method of claim 28, wherein B is substituted or unsubstituted phenylene.

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

31. The method of claim 28, wherein B is substituted or unsubstituted pyridinylene, pyrimidinylene, or pyridazine.

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

33. The method of claim 18, wherein said compound corresponds to Formula (XIII):

34. The method of claim 33, wherein B of said compound is a substituted or unsubstituted six-membered heteroarylene.

35. The method of claim 34, wherein said six-membered heteroarylene is substituted or unsubstituted pyrimidinylene.

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

37. The method of claim 18, wherein L of said compound —

OCR₂—

.

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

39. The method of claim 14, wherein L of said compound is —

C(O)NH.

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

41. The method of claim 14, wherein said compound is selected from the group consisting of:

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

43. The method of claim 42, wherein said compound corresponds to Formula (XV):

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

C(O)NH—

, or —

O(substituted or unsubstituted alkylene)-.

45. The method of claim 44, wherein

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

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

48. The method of claim 47, wherein said compound corresponds to Formula (XVII):

49. The method of claim 48, wherein said compound is:

50. The method of claim 48, wherein said compound corresponds to Formula (XVIII):

51. The method of claim 50, wherein said compound is selected from the group consisting of:

52. The method of claim 48, wherein said compound corresponds to Formula (XXI):

53. The method of claim 52, wherein said compound is selected from the group consisting of:

54. The method of claim 48, wherein said compound corresponds to Formula (XXII):

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

56. The method of claim 48, wherein said compound corresponds to Formula (XXIII):

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

58. The method of claim 48, wherein said compound corresponds to Formula (XXIV):

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

60. The method of claim 48, wherein said compound corresponds to Formula (XXV):

61. The method of claim 60, wherein L of said compound is —

O(substituted or unsubstituted alkylene)- or —

O(substituted or unsubstituted alkenylene)-.

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

63. The method of claim 60, wherein L of said compound is —

NHC(O)—

.

64. The method of claim 63, wherein said compound is selected from the group consisting of:

65. The method of claim 60, wherein L of said compound is a covalent bond, substituted or unsubstituted alkylene, —

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

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

NH(alkylene)-, —

NHC(O)CH₂SCH₂C(O)NH—

, and —

NHC(O)(substituted alkylene)S—

.

66. The method of claim 65, wherein said compound is selected from the group consisting of:

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

68. The method of claim 67, wherein said compound corresponds to Formula (XXVII):

69. The method of claim 68, wherein said compound is selected from the group consisting of:

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

71. The method of claim 70, wherein said compound corresponds to Formula (XIX):

72. The method of claim 71, wherein said compound corresponds to Formula (XX):

73. The method of claim 72, wherein said compound is selected from the group consisting of:

74. The method of claim 71, wherein said compound corresponds to Formula (XXXI):

78. The method of claim 71, wherein said compound is selected from the group consisting of:

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

80. The method of claim 79, wherein said compound corresponds to Formula (XXIV):

81. The method of claim 80, wherein said compound is selected from the group consisting of:

82. The method of claim 80, wherein said compound corresponds to Formula (XXV)

83. The method of claim 82, wherein said compound is selected from the group consisting of:

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

85. The method of claim 84, wherein said compound corresponds to Formula (B):

86. The method of claim 84, wherein said compound is selected from the group consisting of:

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

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

76. The method of claim 75, wherein U is a substituted or unsubstituted five-membered heteroaryl, substituted or unsubstituted phenyl, or substituted or unsubstituted six-membered heteroaryl.

77. The method of claim 76, wherein said compound is selected from the group consisting of:

89. A method of treating a flt-3. mediated disease, said method comprising administering a therapeutically effective amount of a compound corresponding to Formula (IA):