Urea derivatives as PDGFR modulators

• US 20050197371A1
• Filed: 11/15/2004
• Published: 09/08/2005
• 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:
  US10/990,194
• Publication Number:
  US 20050197371A1
• 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 PDGFR. 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 PDGF-R 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 5, wherein said compound corresponds to Formula (V):

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

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

10. The method of claim 9, wherein said compound corresponds to Formula (VII):

11. The method of claim 9, wherein said compound corresponds to Formula (VIII):

12. The method of claim 11, wherein said compound is selected from the group consisting of:

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

14. The method of claim 13, wherein T of said compound corresponds to Formula (X):

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

16. The method of claim 15, 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)-.

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

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 five-membered heteroarylene is substituted or unsubstituted thiophenylene.

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

21. The method of claim 18, wherein B is substituted or unsubstituted imidazolylene.

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

23. The method of claim 18, wherein B is substituted or unsubstituted pyrrolylene.

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

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

26. The method of claim 25, wherein B is substituted or unsubstituted phenylene.

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

28. The method of claim 25, wherein B is substituted or unsubstituted pyridinylene or isopyridazine.

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

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

31. The method of claim 30, wherein B of said compound is a substituted or unsubstituted six-membered heteroarylene.

32. The method of claim 31, wherein said six-membered heteroarylene is substituted or unsubstituted pyrimidinylene.

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

34. The method of claim 16, wherein L of said compound —

OCH₂—

.

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

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

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

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

39. The method of claim 38, wherein L of said compound is a covalent bond, —

C(O)NH—

, or —

O(substituted or unsubstituted alkylene)-.

40. The method of claim 39, wherein

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

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

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

44. The method of claim 43, wherein L is a linker selected from the group consisting of a covalent bond, -substituted or unsubstituted alkylene)-, —

NHC(O)—

, —

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

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

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

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

O(substituted or unsubstituted alkylene)-.

45. The method of claim 44, wherein said compound is:

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

47. The method of claim 46, wherein said compound corresponds to Formula (XIX):

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

49. The method of claim 46, wherein said compound corresponds to Formula (XX):

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

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

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

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

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

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

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

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

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

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

60. The method of claim 59, wherein L of said compound is —

OCH₂—

or —

OCH₂CHCH—

.

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

62. The method of claim 59, wherein L of said compound is —

NHC(O)—

.

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

64. The method of claim 59, wherein L of said compound is a covalent bond, substituted or unsubstituted alkylene, —

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)-.

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

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

67. The method of claim 66, wherein said compound corresponds to Formula (XXVII):

68. The method of claim 67, wherein said compound is

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

70. The method of claim 69, wherein said compound corresponds to Formula (XXIX):

71. The method of claim 70, wherein said compound is

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

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

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

75. The method of claim 74, wherein V is a five-membered hetroarylene group.

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:

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

79. A method for treating a disease mediated by PDGF-R kinase, said method comprising administering a therapeutically effective amount of a compound corresponding to Formula (IA):