Claims
- 1. A compound of formula I
- 2. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein
M1 is aryl, heteroaryl or heterocycloalkyl; and M2 is aryl, cycloalkyl, heteroaryl, or heterocyclyl.
- 3. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X is selected from the group consisting of hydrogen, alkoxy, —CF3, haloalkoxy, halogen, —OCF3, —OCF2H and —OH.
- 4. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Y is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, —C(O)OR2, cycloalkyl, halogen, —N(R2)2, —OCF3, —O-cycloalkyl and —OH.
- 5. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, —C(O)OR2, halogen, heterocyclyl, —N(R2)2, —OCF3, —O-cycloalkyl and —OH.
- 6. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is selected from the group consisting of hydrogen, alkoxy, alkyl, cycloalkyl and —N(R2)2.
- 7. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl and heterocycloalkyl.
- 8. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein L1 is selected from the group consisting of —C(R2)2—, —N(R2)S(O2)—, —N(R2)—, —S(O2)— and —S(O2)N(R2)—.
- 9. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein L2 is selected from the group consisting of a covalent bond, —C(R2)2—, —N(R2)S(O2)—, —N(R2)—, —S(O2)— and —S(O2)N(R2)—.
- 10. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein M1 is aryl, heteroaryl or heterocyclyl.
- 11. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein M2 is aryl, cycloalkyl, heteroaryl, or heterocyclyl.
- 12. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein
X is selected from the group consisting of hydrogen, alkoxy, —CF3, haloalkoxy, halogen, —OCF3, —OCF2H and —OH; Y is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, —C(O)OR2, cycloalkyl, halogen, —N(R2)2, —OCF3, —O-cycloalkyl and —OH; Z is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, —C(O)OR2, halogen, heterocyclyl, —N(R2)2, —OCF3, —O-cycloalkyl and —OH; R1 is selected from the group consisting of hydrogen, alkoxy, alkyl, cycloalkyl and-N(R2)2; R2 is selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl and heterocyclyl; L1 is selected from the group consisting of —C(R2)2—, —N(R2)—, —S(O2)— and —S(O2)N(R2)—; L2 is selected from the group consisting of a covalent bond, —C(R2)2—, —N(R2)S(O2)—, —N(R2)—, —S(O2)— and —S(O2)N(R2)—; M1 is aryl, heteroaryl or heterocyclyl; M2 is aryl, cycloalkyl, heteroaryl, or heterocyclyl; with the provisos that: the two R2 moieties of N(R2)2 and C(R2)2— are the same or different and are independently selected, wherein each R2 of N(R2)2 are joined together and with the nitrogen to which they are attached form a heterocyclic ring having 3 to 7 ring atoms; wherein each of said alkoxy, alkyl, aralkyl, aryl, cycloalkyl, heteroaralkyl, heteroaryl and heterocyclyl in the definitions above can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkoxy, —CF3, —CN, —C(O)N(R2)2, —C(O)OR2, —C(O)R2—, —NC(O)R2, —NR2C(O)OR2, —NR2C(O)N(R2)2, —NC(═N—CN)NHR2, —NO2, —N(R2)2, —OCF2H, —OCF3, —OH, —S(O2)R2 and —S(O2)N(R2)2.
- 13. The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein
n is 1; X is hydrogen and —OH; Y is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, —C(O)OR2, cycloalkyl, halogen, —N(R2)2, —OCF3 and —OH; Z is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, —C(O)OR2, halogen, heterocyclyl, —N(R2)2, —OCF3, —O-cycloalkyl and —OH; R1 is selected from the group consisting of hydrogen, alkoxy, alkyl, cycloalkyl and —N(R2)2; R2 is selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl and heterocyclyl; L1 is selected from the group consisting of —C(O)—, —C(R2)2— and —S(O2)—; L2 is selected from the group consisting of a covalent bond, —C(R2)2—, —C(O)— and —S(O2)—; M1 is aryl, heteroaryl or heterocyclyl; and M2 is aryl, cycloalkyl, heteroaryl, or heterocyclyl.
- 14. The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein
n is 1; X is hydrogen and —OH; Y is selected from the group consisting of hydrogen, alkoxy, alkyl, —C(O)OR2, cycloalkyl, —CF3, halogen, —OCF3 and —OH; Z is selected from the group consisting of hydrogen, alkoxy, alkyl, —CF3, halogen, —OCF3, —O-cycloalkyl and —OH; R1 is selected from the group consisting of hydrogen, alkoxy, alkyl, cycloalkyl and —N(R2)2; R2 is selected from the group consisting of hydrogen, alkyl, aryl and cycloalkyl; L1 and L2 are the same or different and are independently —C(R2)2— or —S(O2)—; M1 is aryl or heteroaryl; and M2 is aryl, cycloalkyl, heteroaryl or heterocyclyl.
- 15. The compound according to claim 1 having the formula II:
- 16. The compound according to claim 15 having the formula II, or a pharmaceutically acceptable salt thereof, wherein R1, L1, M1, M2, Y and Z are as set forth in the following table:
- 17. The compound according to claim 1 having the formula III:
- 18. The compound according to claim 1 having the formula IV
- 19. The compound according to claim 1 having the formula V
- 20. The compound of claim 1 having the formula VI
- 21. The compound of claim 1 having the formula:
- 22. A pharmaceutical composition comprising an effective amount of at least one compound according to claim 1 and a pharmaceutically acceptable carrier.
- 23. A pharmaceutical composition comprising an effective amount of at least one compound according to claim 16 and a pharmaceutically acceptable carrier.
- 24. A method of treating cancer, inflammatory diseases, immunomodulatory diseases, or respiratory diseases comprising administering to a mammal in need of such treatment an effective amount of at least one compound according to claim 1.
- 25. A method of treating cancer, inflammatory diseases, immunomodulatory diseases, or respiratory diseases comprising administering to a mammal in need of such treatment an effective amount of at least one compound according to claim 16.
- 26. A method of treating cutaneous T cell lymphoma, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, glaucoma, diabetes, sepsis, shock, 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, Crohn's disease, inflammatory bowel disease, reversible airway obstruction, adult respiratory distress syndrome, asthma, chronic obstructive pulmonary disease (COPD) or bronchitis comprising administering to a mammal in need of such treatment an effective amount of at least one compound according to claim 1.
- 27. A method of treating cutaneous T cell lymphoma, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, glaucoma, diabetes, sepsis, shock, 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, Crohn's disease, inflammatory bowel disease, reversible airway obstruction, adult respiratory distress syndrome, asthma, chronic obstructive pulmonary disease (COPD) or bronchitis comprising administering to a mammal in need of such treatment an effective amount of at least one compound according to claim 16.
- 28. The method of claim 24 wherein the condition or disease treated is selected from rheumatoid arthritis, multiple sclerosis, seasonal allergic rhinitis, psoriasis, transplant rejection and chronic obstructive pulmonary disease.
- 29. The method of claim 25 wherein the condition or disease treated is selected from rheumatoid arthritis, multiple sclerosis, seasonal allergic rhinitis, psoriasis, transplant rejection and chronic obstructive pulmonary disease.
- 30. A process for making a pharmaceutical composition comprising combining at least one compound of claim 1 and at least one pharmaceutically acceptable carrier.
- 31. A process for making a pharmaceutical composition comprising combining at least one compound of claim 16 and at least one pharmaceutically acceptable carrier.
- 32. A method of treating rheumatoid arthritis comprising administering to a mammal in need thereof an effective amount of at least one compound of claim 1 in combination with at least one compound selected from the class consisting of a COX-2 inhibitor, a COX-1 inhibitor, an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of rheumatoid arthritis.
- 33. A method of treating rheumatoid arthritis comprising administering to a mammal in need thereof an effective amount of at least one compound of claim 16 in combination with at least one compound selected from the class consisting of a COX-2 inhibitor, a COX-1 inhibitor, an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of rheumatoid arthritis.
- 34. The method of claim 32 wherein the COX-2 inhibitor is Celebrex or Vioxx, the COX-1 inhibitor is Feldene, the immunosuppressive is methotrexate, leflunomide, sulfasalazine, or cyclosporin, the steroid is β-methasone and the anti-TNF-αcompound is Enbrel or Remicade.
- 35. The method of claim 33 wherein the COX-2 inhibitor is Celebrex or Vioxx, the COX-1 inhibitor is Feldene, the immunosuppressive is methotrexate, leflunomide, sulfasalazine, or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 36. A composition for treating rheumatoid arthritis which comprises a compound selected from the class consisting of a COX-2 inhibitor, a COX-1 inhibitor, an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of rheumatoid arthritis and an effective amount of at least one compound of claim 1.
- 37. A composition for treating rheumatoid arthritis which comprises a compound selected from the class consisting of a COX-2 inhibitor, a COX-1 inhibitor, an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of rheumatoid arthritis and an effective amount of at least one compound of claim 16.
- 38. The composition of claim 36 wherein the COX-2 inhibitor is Celebrex or Vioxx, the COX-1 inhibitor is Feldene, the immunosuppressive is methotrexate, leflunomide, sulfasalazine, or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 39. The composition of claim 37 wherein the COX-2 inhibitor is Celebrex or Vioxx, the COX-1 inhibitor is Feldene, the immunosuppressive is methotrexate, leflunomide, sulfasalazine, or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 40. A method of treating multiple sclerosis comprising administering to a mammal in need thereof an effective amount of at least one compound of claim 1 in combination with an effective amount of a compound selected from Avonex, Betaseron, Copaxone or other compounds indicated for the treatment of multiple sclerosis.
- 41. A method of treating multiple sclerosis comprising administering to a mammal in need thereof an effective amount of at least one compound of claim 16 in combination with an effective amount of a compound selected from Avonex, Betaseron, Copaxone or other compounds indicated for the treatment of multiple sclerosis.
- 42. A composition for treating multiple sclerosis which comprises a compound selected from Avonex, Betaseron, Copaxone or other compounds indicated for the treatment of multiple sclerosis and an effective amount of at least one compound of claim 1.
- 43. A composition for treating multiple sclerosis which comprises a compound selected from Avonex, Betaseron, Copaxone or other compounds indicated for the treatment of multiple sclerosis and an effective amount of at least one compound of claim 16.
- 44. A method of treating psoriasis comprising administering to a mammal in need thereof an effective amount of at least one compound as defined in claim 1 in combination with a compound selected from the class consisting of an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of psoriasis.
- 45. A method of treating psoriasis comprising administering to a mammal in need thereof an effective amount of at least one compound as defined in claim 16 in combination with a compound selected from the class consisting of an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of psoriasis.
- 46. The method of claim 44 wherein the immunosuppressive is methotrexate, leflunomide, sulfasalazine or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 47. The method of claim 45 wherein the immunosuppressive is methotrexate, leflunomide, sulfasalazine or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 48. A composition for treating psoriasis which comprises a compound selected from the class consisting of an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of psoriasis and an effective amount of at least one compound of claim 1.
- 49. A composition for treating psoriasis which comprises a compound selected from the class consisting of an immunosuppressive, a steroid, an anti-TNF-α compound or other classes of compounds indicated for the treatment of psoriasis and an effective amount of at least one compound of claim 16.
- 50. The composition of claim 48 wherein the immunosuppressive is methotrexate, leflunomide, sulfasalazine or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 51. The composition of claim 49 wherein the immunosuppressive is methotrexate, leflunomide, sulfasalazine or cyclosporin, the steroid is β-methasone and the anti-TNF-α compound is Enbrel or Remicade.
- 52. A method of treating seasonal allergic rhinitis and/or asthma comprising an effective amount of at least one compound of claim 1 in combination with at least one H1 antagonist.
- 53. A method of treating seasonal allergic rhinitis and/or asthma comprising an effective amount of at least one compound of claim 16 in combination with at least one H1 antagonist.
- 54. A composition for treating seasonal allergic rhinitis and/or asthma which comprises an effective amount of at least one H1 antagonist and an effective amount of at least one compound of claim 1.
- 55. A composition for treating seasonal allergic rhinitis and/or asthma which comprises an effective amount of at least one H1 antagonist and an effective amount of at least one compound of claim 16.
- 56. The composition of claim 54 wherein the H1 antagonist is selected from Claritin, Clarinex, Zyrtec and Allegra.
- 57. The composition of claim 55 wherein the H1 antagonist is selected from Claritin, Clarinex, Zyrtec and Allegra.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of priority from U.S. Provisional Patent Application Serial No. 60/456,268, filed Mar. 20, 2003.
Provisional Applications (1)
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Number |
Date |
Country |
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60456268 |
Mar 2003 |
US |