Claims
- 1. A compound represented by Formula (I):
- 2. The compound according to claim 1, wherein m is 4.
- 3. The compound according to claim 1, wherein m is 3.
- 4. The compound according to claim 1, wherein m is 2.
- 5. The compound according to claim 1, wherein m is 1.
- 6. The compound according to claim 1, wherein R30 is H or —(C1-C6)alkyl.
- 7. The compound according to claim 1, wherein R40 is H or —(C1-C6)alkyl.
- 8. The compound according to claim 1, wherein T is selected from the group consisting of —C(O)R4, —C(O)OR3, —C(O)NR23R25, and —C(O)NR23OR3.
- 9. The compound according to claim 8, wherein T is —C(O)R4 in which R4 is a pyrrolidinyl ring that is unsubstituted or substituted with one to three R22 moieties which are each independently selected from the group consisting of —OR24, —(C1-C6 alkyl)-OR24 and —NR23R24.
- 10. The compound according to claim 8, wherein T is —C(O)OR3 in which R3 is alkyl.
- 11. The compound according to claim 8, wherein T is —C(O)NR23R25 in which R23 is H or alkyl and R25 is H, alkyl or —(C1 to C6 alkyl)NR23N24.
- 12. The compound according to claim 8, wherein T is —C(O)NR23OR3 in which R23 is H or alkyl and R3 is H or alkyl.
- 13. The compound according to claim 1, wherein V is —C(O)NR23OR3 in which R23 is H or alkyl and R3 is H or alkyl.
- 14. The compound according to claim 1, wherein V is —C(O)OR3 in which R3 is alkyl.
- 15. The compound according to claim 1, wherein W is —C(R3)(R4)— in which R3 is H and R4 is H.
- 16. The compound according to claim 1, wherein W is a covalent bond.
- 17. The compound according to claim 1, wherein n is 1.
- 18. The compound according to claim 1, wherein X is arylene which is unsubstituted or substituted with one to two independently selected R20 moieties which can be the same or different.
- 19. The compound according to claim 18, wherein X is phenylene which is unsubstituted or substituted with one or two halo substituents which can be the same or different.
- 20. The compound according to claim 1, wherein X is a heteroarylene which is unsubstituted or substituted with one to two independently selected R20 moieties which can be the same or different.
- 21. The compound according to claim 20, wherein X is a heteroarylene selected from the group consisting of
- 22. The compound according to claim 1, wherein U is —Y—(C(R3)(R4))q—.
- 23. The compound according to claim 22, wherein Y is —O—.
- 24. The compound according to claim 22, wherein q is 1, R3 is H or alkyl and R4 is H or alkyl.
- 25. The compound according to claim 1, wherein R1 is selected from the group consisting of cycloalkyl, aryl and heteroaryl, wherein each of the cycloalkyl, aryl and heteroaryl groups of R1 is independently unsubstituted or substituted with one to five independently selected R20 moieties which can be the same or different, each R20 moiety being independently selected from the group of R20 moieties,
- 26. The compound according to claim 25, wherein R1 is a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl and cyclohexyl, wherein each of the cycloalkyl groups is independently unsubstituted or substituted with one to five independently selected R20 moieties which can be the same or different, each R20 moiety being independently selected from the group of R20 moieties.
- 27. The compound according to claim 25, wherein R1is an aryl group selected from the group consisting of phenyl, naphthyl, indanyl and tetrahydronaphthalenyl, wherein each of the aryl groups is independently unsubstituted or substituted with one to five independently selected R20 moieties which can be the same or different, each R20 moiety being independently selected from the group of R20 moieties.
- 28. The compound according to claim 25, wherein R1 is a heteroaryl group selected from the group consisting of chromanyl, quinolyl, isoquinolyl, triazolyl, pyridyl, imidazolyl, thiazolyl, benzodioxolyl and
- 29. The compound according to claim 25, wherein R1 is (1) a fused bicyclic aryl group which is unsubstituted or substituted with one to three independently selected R20 moieties which can be the same or different or (2) a fused bicyclic heteroaryl group which is unsubstituted or substituted with one to three independently selected R20 moieties which can be the same or different.
- 30. The compound according to claim 1, wherein R2 is H.
- 31. The compound according to claim 1, wherein each R3 is independently H, alkyl or aryl.
- 32. The compound according to claim 1, wherein each R4 is independently H, alkyl or aryl.
- 33. The compound according to claim 1, wherein each R5 is independently H, alkyl or aryl.
- 34. The compound according to claim 1, wherein each R20 is independently selected from the group consisting of alkyl, R21-substituted alkyl, —OR3, halo, —CN, —NO2, —NR3R4, —C(O)OR3, —S(O)xR5, —CF3, —OCF3, aryl, heteroaryl, cycloalkyl, wherein each of the aryl, heteroaryl and cycloalkyl groups of R20 is independently unsubstituted or substituted with one to four independently selected R22 moieties which can be the same or different, each R22 moiety being independently selected from the group of R23 moieties.
- 35. The compound according to claim 34, wherein R20 is a heteroaryl group selected from the group consisting of pyrazinyl, pyrrolyl, pyridyl and morpholinyl.
- 36. The compound according to claim 34, wherein R20 is a cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl and cyclohexyl.
- 37. The compound according to claim 34, wherein each R20 moiety is selected from the group consisting of —(C1-C6)alkyl and aryl.
- 38. The compound according to claim 1, wherein
M is —(C(R30)(R40)m—, wherein m is 1 to 4; V is —C(O)OR3 or —C(O)NR25OR3; T is R21-substituted alkyl, —CN, —C(O)OR3, —C(O)NR25OR3, —C(O)NR24R25, —C(O)R4 or —C(R4)(═N(OR3)); W is a covalent bond or —(C(R3)(R4))n2; X is arylene or heteroarylene, each of which can be independently unsubstituted or substituted with one to five independently selected R20 moieties; R1 is cycloalkyl, aryl, heteroaryl, each of which can be independently unsubstituted or substituted with one to four independently selected R20 moieties; and R2 is H.
- 39. The compound according to claim 38, wherein m is 1.
- 40. The compound according to claim 39, wherein m is 2.
- 41. The compound according to claim 38, wherein R30 is H or —(C1-C6)alkyl and R40 is H or —(C1-C6)alkyl.
- 42. The compound according to claim 38, wherein T is selected from the group consisting of —C(O)R4, —C(O)OR3, —C(O)NR23R25, and —C(O)NR23OR3.
- 43. The compound according to claim42, wherein T is —C(O)OR3 or —C(O)NR23R25.
- 44. The compound according to claim 38, wherein V is —C(O)NR23OR3 in which R23 is H or alkyl and R3 is H or alkyl.
- 45. The compound according to claim 38, wherein W is —C(R3)(R4)— in which n2 is 1, R3 is H and R4 is H or W is a covalent bond.
- 46. The compound according to claim 38, wherein X is arylene which is unsubstituted or substituted with one to two independently selected R20 moieties which can be the same or different.
- 47. The compound according to claim 38, wherein U is —Y—(C(R3)(R4))q—.
- 48. The compound according to claim 47, wherein Y is —O—, q is 1, R3 is H or alkyl and R4 is H or alkyl.
- 49. The compound according to claim 38, wherein R1 is selected from the group consisting of aryl and heteroaryl, wherein each of the aryl and heteroaryl groups of R1 is independently unsubstituted or substituted with one to five independently selected R20 moieties which can be the same or different, each R20 moiety being independently selected from the group of R20 moieties,
- 50. The compound according to claim 49, wherein R1 is an aryl group selected from the group consisting of phenyl, naphthyl, indanyl and tetrahydronaphthalenyl, wherein each of the aryl groups is independently unsubstituted or substituted with one to five independently selected R20 moieties which can be the same or different, each R20 moiety being independently selected from the group of R20 moieties.
- 51. The compound according to claim 49, wherein R1 is a heteroaryl group selected from the group consisting of chromanyl, quinolyl, isoquinolyl,
- 52. The compound according to claim 38, wherein each R3 is independently H, alkyl or aryl, wherein the alkyl or aryl groups can be unsubstituted or substituted with one to four independently selected R22 moieties.
- 53. The compound according to claim 38, wherein each R4 is independently H, alkyl or aryl.
- 54. The compound according to claim 38, wherein each R5 is independently H, alkyl or aryl.
- 55. The compound according to claim 38, wherein each R20 is independently selected from the group consisting of alkyl, R21-substituted alkyl, —OR3, halo, —CN, —NO2, —NR3R4, —C(O)OR3, —S(O)xR5, —CF3, —OCF3, aryl, heteroaryl, cycloalkyl, wherein each of the aryl, heteroaryl and cycloalkyl groups of R20 is independently unsubstituted or substituted with one to four independently selected R22 moieties which can be the same or different, each R22 moiety being independently selected fromthe group of R23 moieties.
- 56. A compound selected from the group consisting of:
- 57. A compound according to claim 56, which is selected from the group consisting of
- 58. A compound represented by Formula (I):
- 59. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable addition salt, solvate or isomer thereof, in combination with a pharmaceutically acceptable carrier.
- 60. A pharmaceutical composition for the treatment or prevention of inflammation in a subject, comprising an effective amount of a combination of a compound of claim 1 or a pharmaceutically acceptable salt, solvate or isomer thereof, an anti-inflammatory agent different from the compound of claim 1 and a pharmaceutically acceptable carrier.
- 61. A method for treating or preventing an inflammatory disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, solvate or isomer thereof.
- 62. A method of treating a condition or disease mediated by MMPs, TNF-α, aggrecanase, or a combination thereof in a subject comprising:
administering to the subject in need of such treatment a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, solvate or isomer thereof.
- 63. A method of treating a condition or disease selected from the group consisting of rheumatoid arthritis, osteoarthritis, periodontitis, gingivitis, corneal ulceration, solid tumor growth and tumor invasion by secondary metastases, neovascular glaucoma, inflammatory bowel disease, multiple sclerosis and psoriasis in a subject, comprising: administering to the subject in need of such treatment a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, solvate or isomer thereof.
- 64. A method of treating a condition or disease selected from the group consisting of fever, cardiovascular conditions, hemorrhage, coagulation, cachexia, anorexia, alcoholism, acute phase response, acute infection, shock, graft versus host reaction, autoimmune disease and HIV infection in a subject comprising administering to the subject in need of such treatment a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, solvate or isomer thereof.
- 65. A method of treating a condition or disease selected from the group consisting of septic shock, haemodynamic shock, sepsis syndrome, post ischaemic reperfusion injury, malaria, mycobacterial infection, meningitis, psoriasis, congestive heart failure, fibrotic diseases, cachexia, graft rejection, cancers such as cutaneous T-cell lymphoma, diseases involving angiogenesis, autoimmune diseases, skin inflammatory diseases, inflammatory bowel diseases such as Crohn's disease and colitis, osteo and rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, adult Still's disease, ureitis, Wegener's granulomatosis, Behcehe disease, Sjogren's syndrome, sarcoidosis, polymyositis, dermatomyositis, multiple sclerosis, radiation damage, hyperoxic alveolar injury, periodontal disease, HIV, non-insulin dependent diabetes mellitus, systemic lupus erythematosus, glaucoma, sarcoidosis, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, retinal disease, scleroderma, osteoporosis, renal ischemia, myocardial infarction, cerebral stroke, cerebral ischemia, nephritis, hepatitis, glomerulonephritis, cryptogenic fibrosing aveolitis, psoriasis, transplant rejection, atopic dermatitis, vasculitis, allergy, seasonal allergic rhinitis, reversible airway obstruction, adult respiratory distress syndrome, asthma, chronic obstructive pulmonary disease (COPD) and bronchitis in a subject comprising administering to the subject in need of such treatment a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, solvate or isomer thereof.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of priority from U.S. Provisional Patent Application Serial No. 60/342,332, filed Dec. 20, 2001, incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60342332 |
Dec 2001 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
10323511 |
Dec 2002 |
US |
Child |
10716890 |
Nov 2003 |
US |