Claims
- 1. A method of treating or inhibiting arthritis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of a non-uterotrophic, non-mammotrophic ERβ selective ligand, wherein the binding affinity of the ER-β selective ligand to ER-β is at least about 20 times greater than its binding affinity to ER-α, and an anti-arthritis agent.
- 2. The method according to claim 1, wherein the arthritis is rheumatoid arthritis, osteoarthritis, or spondyloarthropathies.
- 3. The method according to claim 2, wherein the binding affinity of the ERβ selective ligand to ERβ is at least about 50 times greater than its binding affinity to ERα.
- 4. The method according to claim 3, wherein the ERβ selective ligand causes an increase in wet uterine weight which is less than about 10% of that observed for a maximally efficacious dose of 17β-estradiol, and the ERβ selective ligand has activity that is <10% as efficacious as 17beta-estradiol at facilitating the development of lobular-alveolar end buds as assessed by histological examination.
- 5. The method according to claim 4, wherein the ERβ selective ligand does not significantly increase wet uterine weight compared with a control that is devoid of uterotrophic activity, and does not significantly facilitate the development of lobular-alveolar end buds compared with a control that is devoid of mammotrophic activity.
- 6. The method according to claim 1, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease modifying antirheumatic drug.
- 7. The method according to claim 6, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 8. The method according to claim 5, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease modifying antirheumatic drug.
- 9. The method according to claim 8, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, or q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 10. A method of treating or inhibiting joint swelling or erosion; or treating or inhibiting joint damage secondary to arthroscopic or surgical procedures in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of a non-uterotrophic, non-mammotrophic ERβ selective ligand, wherein the binding affinity of the ER-β selective ligand to ER-β is at least about 20 times greater than its binding affinity to ER-α, and an anti-arthritis agent.
- 11. The method according to claim 10, wherein the binding affinity of the ERβ selective ligand to ERβ is at least about 50 times greater than its binding affinity to ERα.
- 12. The method according to claim 11, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease modifying antirheumatic drug.
- 13. The method according to claim 12, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, or q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 14. A method of treating or inhibiting arthritis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of a compound of formula I, having the structure
- 15. The method according to claim 14, wherein X is O.
- 16. The method according to claim 15, wherein R1 is alkenyl of 2-3 carbon atoms, which is optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR5, —CO2R5, —NO2, CONR5R6, NR5R6 or N(R5)COR6.
- 17. The method according to claim 14, the compound of formula I is 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol or a pharmaceutically acceptable salt thereof.
- 18. The method according to claim 14, wherein the arthritis is rheumatoid arthritis, osteoarthritis, or spondyloarthropathies.
- 19. The method according to claim 17, wherein the arthritis is rheumatoid arthritis, osteoarthritis, or spondyloarthropathies.
- 20. The method according to claim 14, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease mofifying anthrheumatic drug.
- 21. The method according to claim 20, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, or q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 22. The method according to claim 17, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease mofifying anthrheumatic drug.
- 23. The method according to claim 22, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, or q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 24. A method of treating or inhibiting joint swelling or erosion; or treating or inhibiting joint damage secondary to arthroscopic or surgical procedures in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol or a pharmaceutically acceptable salt thereof, and an anti-arthritis agent.
- 25. A method of treating or inhibiting arthritis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of a compound of formula II, having the structure
- 26. The method according to claim 25, wherein the compound of formula II has the structure
- 27. The method according to claim 26 wherein the 5 or 6-membered heterocyclic ring having 1 to 4 heteroatoms selected from O, N or S is furan, thiophene, or pyridine or a pharmaceutically acceptable salt thereof.
- 28. The method according to claim 27, wherein R5, R6, R7, R8, and R9 are each, independently, hydrogen, halogen, —CN, or alkynyl of 2-7 carbon atoms or a pharmaceutically acceptable salt thereof.
- 29. The method according to claim 28, wherein R6, R7, and R8 are hydrogen, or a pharmaceutically acceptable salt thereof.
- 30. The method according to claim 25, wherein the compound of formula II is 3-(3-fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile or a pharmaceutically acceptable salt thereof.
- 31. The method according to claim 25, wherein the arthritis is rheumatoid arthritis, osteoarthritis, or spondyloarthropathies.
- 32. The method according to claim 30, wherein the arthritis is rheumatoid arthritis, osteoarthritis, or spondyloarthropathies.
- 33. The method according to claim 25, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease mofifying anthrheumatic drug.
- 34. The method according to claim 33, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, or q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 35. The method according to claim 30, wherein the anti-arthritis agent is useful in treating the signs and symptoms of arthritis or is a disease mofifying anthrheumatic drug.
- 36. The method according to claim 35, wherein the anti-arthritis agent is:
a) a steroidal antiinflammatory agent, b) sulfasalazine, c) methotrexate, d) auranofin, e) D-penicillamine, f) a COX-2 inhibitor, g) an NSAID, i) a P38 MAP kinase inhibitor, j) a TNFα inhibitor, k) a IL1β converting enzyme inhibitor, l) a VLA4 antagonist, m) a NFκB inhibitor, n) an immunomodulator, o) a IL1 receptor antagonist, p) an antibiotic, or q) a statin, r) cyclophosphamide, s) hydroxychloroquine, or t) chlorambusil.
- 37. A method of treating or inhibiting joint swelling or erosion; or treating or inhibiting joint damage secondary to arthroscopic or surgical procedures in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of 3-(3-fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile or a pharmaceutically acceptable salt thereof, and an anti-arthritis agent.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority benefit of U.S. Provisional Application Ser. No. 60/472,382, filed May 21, 2003, the entire content of which is incorporated by reference herein.
Provisional Applications (1)
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Number |
Date |
Country |
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60472382 |
May 2003 |
US |