Pyrazolo[1,5-a]pyrimidines useful as inhibitors of protein kinases

• US 20060135537A1
• Filed: 11/04/2005
• Published: 06/22/2006
• Est. Priority Date: 11/04/2004
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Jimenez, Juan-Miguel, Come, Jon, Stamos, Dean, Li, Pan, Knegtel, Ronald, Charrier, Jean-Damien, Aronov, Alex
• Granted Patent: US 7,528,138 B2
• Time in Patent Office: Days
• US Class Current: 514/259.300
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• 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 487/04 : Ortho-condensed systems
• CPC Class Codes: C07F 9/6561 : containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Abstract

The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing the compounds of the invention.

Claims

1-30. -30. (canceled)

31. A compound selected from any one of Tables 1-4.

32-38. -38. (canceled)

39. A compound of formula I′

;

41. The compound according to claim 39, wherein R⁴ is H and R³ is other than H.

42. The compound according to claim 39, wherein Z is a bond.

43. The compound according to claim 39, wherein R′

is H.

44. The compound according to claim 39, wherein R is

48. The compound according to claim 44, wherein R^2a is OR⁵, N(R⁵)₂, or 5-8 membered heterocyclyl.

56. The compound according to claim 39, wherein R is Y.

63. The compound according to claim 39, wherein R³ and R⁴ are each independently U_m-V.

79. The compound according to claim 39, wherein Z is a bond and R is selected from

90. The compound according to claim 39, wherein said compound is of formula II:

92. The compound according to claim 90, wherein said compound is of formula III:

93. The compound according to claim 92, wherein Ring A has the formula

95. The compound according to claim 93, wherein said compound is of formula IV:

104. A composition comprising a compound according to claim 39 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

105. The composition of claim 104, further comprising an additional therapeutic agent selected from an agent for the treatment of an autoimmune, inflammatory, proliferative, hyperproliferative disease, or an immunologically-mediated disease including rejection of transplanted organs or tissues and Acquired Immunodeficiency Syndrome (AIDS).

106. A method of inhibiting Tec family kinase activity in:

(a) a patient;

or

(b) a biological sample;

which method comprises administering to said patient, or contacting said biological sample with a compound according to claim 39 or a composition comprising said compound.

111. A method of inhibiting c-Met protein kinase activity in a patient comprising administering to said patient:

a compound according to claim 39 or a composition comprising said compound.

120. A method of treating melanoma, myeloma, leukemia, lymphoma, neuroblastoma, or a cancer selected from colon, breast, gastric, ovarian, cervical, lung, central nervous system (CNS), renal, prostate, bladder, or pancreatic, in a patient in need thereof wherein said method comprises administering to said patient:

a compound according to claim 39 or a composition comprising said compound.

40. (canceled)

45-47. -47. (canceled)

49-55. -55. (canceled)

57-62. -62. (canceled)

64-78. -78. (canceled)

80-89. -89. (canceled)

91. (canceled)

94. (canceled)

96-102. -102. (canceled)

103. A compound selected from Table 5.

107-110. -110. (canceled)

112-119. -119. (canceled)

121. (canceled)