PHENYL-ANILINE SUBSTITUTED BICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS

• US 20080167304A1
• Filed: 03/13/2008
• Published: 07/10/2008
• Est. Priority Date: 10/22/2003
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Hynes, John, Leftheris, Katerina, Wrobleski, Stephen T., Wu, Hong, Lin, Shuqun, Das, Jagabandhu
• Granted Patent: US 7,642,257 B2
• Time in Patent Office: Days
• US Class Current: 514/234.2
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

Compounds having the formula (I),

and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are useful as kinase inhibitors, wherein R, R₁, R₂, R₅, R_6a, R_6b, J, K, X and Z are as described in the specification.

Claims

1. A compound having the formula (I)

2. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein:

J, K, R₁ and R₂ are selected such that ring D and the ring fused thereto as defined by

R₁ and R₂ form a bicyclic group selected from one of;

3. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein R₁ and R₂ taken together (with K, the C* atom, and the bond joining K and C*), form S₁, S₂ or S₃, and J is N.

4. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein R₁ and R₂ taken together (with K, the C* atom, and the bond joining K and C*), form T₁ or T₂, and J is CH.

5. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein R₁ and R₂ taken together (with K, the C* atom, and the bond joining K and C*), form T₃ and J is N.

6. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein,

R₅ is hydrogen;

R_6a is methyl; and

R_6b is hydrogen.

7. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein,

Z is selected from —

C(═

O)NR₁₁R₁₂, —

NR₁₁C(O)₂R₁₂, —

NR₁₁(C═

O)NHR₁₂, and five membered heteroaryl optionally substituted with C_1-4alkyl;

R₁₁ is hydrogen or C_1-4alkyl;

R₁₂ is C_1-4alkyl, C_1-4alkoxy, cyclopropyl, halo(C_1-4alkyl), or a heteroaryl selected from pyrazolyl, oxazolyl, and isoxazolyl in turn optionally substituted with C_1-4alkyl; and

R₁₃ is selected from phenyl and pyridyl in turn optionally substituted by one to three R₂₆, wherein R₂₆ is selected from halogen, cyano, and morpholinyl.

8. A compound according to claim 7, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein,

Z is —

C(═

O)NR₁₁R₁₂, wherein R₁₁ is hydrogen or C_1-4alkyl, and R₁₂ is selected from C_1-4alkyl, C_1-4alkoxy, and cyclopropyl.

9. A compound according to claim 1, or a pharmaceutically-acceptable salt, prodrug, or solvate thereof, wherein, J, K, R₁ and R₂ are selected to define a compound having a formula I (S1),

10. A compound according to claim 9, having the formula I (S1*):

11. A compound according to claim 9, having the formula I (S1**):

12. A compound according to claim 1, having the formula I (S2):

13. A compound according to claim 12, having the formula I (S2*):

14. A compound according to claim 1, having the formula I (S3):

15. A compound according to claim 14, having the formula I (S3*):

16. A compound according to claim 1, having the formula I (T1):

17. A compound according to claim 16, having the formula I (T1*):

18. A compound according to claim 1, having the formula I (T2):

19. A compound according to claim 18, having the formula I (T2*):

20. A compound according to claim 1, having the formula I (T3):

21. A compound according to claim 20, having the formula I (T3*):

22. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically-acceptable carrier or diluent.

23. A method of treating an inflammatory disorder comprising administering to a patient in need of such treatment a pharmaceutical composition according to claim 22.

24. The method of claim 23 in which the inflammatory disorder is selected from asthma, adult respiratory distress syndrome, chronic obstructive pulmonary disease, chronic pulmonary inflammatory disease, diabetes, inflammatory bowel disease, osteoporosis, psoriasis, graft vs. host rejection, atherosclerosis, and arthritis including rhematoid arthritis, psoriatic arthritis, traumatic arthritis, rubella arthritis, gouty arthritis, osteoarthritis, pain, and neuropathy.