Claims
- 1. A compound of Formula I, and pharmaceutically acceptable salts, hydrates, solvates, and prodrugs thereof:
- 2. The compound according to claim 1, wherein R1 and R2 are independently selected from the group consisting of OH, OCH3, and fluoro.
- 3. The compound according to claim 2, wherein R1 and R2 are both OH.
- 4. The compound according to claim 1, wherein R3 is CH3.
- 5. The compound according to claim 1, wherein R4 is selected from the group consisting of H, phenyl and C1-4alkyl.
- 6. The compound according to claim 5, wherein R4 is selected from the group consisting of H, phenyl, allyl and CH3.
- 7. The compound according to claim 1, wherein R5 is selected from the group consisting of isopropyl, s-butyl, t-butyl, and neopentyl.
- 8. The compound according to claim 7, wherein R5 is t-butyl.
- 9. The compound according to claim 1, wherein the geometry about the C=N double bond of the oxime is trans.
- 10. The compound according to claim 1, wherein both R6 are H.
- 11. The compound according to claim 1, having a relative stereochemistry as shown below:
- 12. The compound according to claim 1 that is selected from the group consisting of:
- 13. The compound according to claim 11 that is selected from he group consisting of compound I(a), I(c), I(e), I(g), I(i) and I(k).
- 14. A compound of Formula II and salts, hydrates and solvates thereof:
- 15. The compound according to claim 14, wherein R1 and R2 are independently selected from the group consisting of OH and OPG.
- 16. The compound according to claim 14, wherein R4 is C1-4alkyl
- 17. The compound according to claim 14, wherein R5 is selected from the group consisting of isopropyl, s-butyl, t-butyl, and neopentyl.
- 18. The compound according to claim 14, selected from the group consisting of:
- 19. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
- 20. A method for treating diseases which benefit from a modulation of the levels of 1α,25-dihydroxy vitamin D3 comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 21. A method for treating diseases which benefit from an inhibition of the catabolism of 1α,25-dihydroxy vitamin D3 comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 22. The method according to claim 19, wherein the disease is selected from the group consisting of cancer, dermatological disorders and bone disorders.
- 23. The method according to claim 22, wherein the disease is selected from the group consisting of cancer, psoriasis and osteoporosis.
- 24. A method for inhibiting cell proliferation comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 25. The method according to claims 24, wherein the cell is a cancer cell.
- 26. The method according to claim 25, wherein the cancer is selected from breast cancer, lung cancer and prostate cancer.
- 27. A method of inhibiting CYP24 activity in a cell by administering an effective amount of a compound according to claim 1.
- 28. A use of a compound according to claim 1 to modulate the levels of 1α,25-dihydroxy vitamin D3.
- 29. A use of a compound according to claim 1 to inhibit the catabolism of 1α,25-dihydroxy vitamin D3.
- 30. A use of a compound according to claim 1 to prepare a medicament to modulate the levels of 1α,25-dihydroxy vitamin D3.
- 31. A use of a compound according to claim 1 to prepare a medicament to inhibit the catabolism of 1α,25-dihydroxy vitamin D3.
- 32. A use of a compound according to claim 1 to inhibit cell proliferation.
- 33. A use of a compound according to claim 1 to prepare a medicament to inhibit cell proliferation.
- 34. A use of a compound according to claim 1 to inhibit CYP24 activity.
- 35. A use of a compound according to claim 1 to prepare a medicament to inhibit CYP24 activity.
- 36. A method for increasing the efficacy of a vitamin D receptor agonist comprising co-administering an effective amount of a compound according to claim 1 and an effective amount of the vitamin D receptor agonist.
- 37. The method according to claim 36, wherein the vitamin D receptor agonist is 1α,25-dihydroxy vitamin D3 (calcitriol).
- 38. A use of a compound according to claim 1 to increase the efficacy of a vitamin D receptor agonist.
- 39. A use of a compound according to claim 1 to prepare a medicament to increase the efficacy of a vitamin D receptor agonist.
- 40. The use according to claim 38, wherein the vitamin D receptor agonist is 1α,25-dihydroxy vitamin D3 (calcitriol).
- 41. The use according to claim 39, wherein the vitamin D receptor agonist is 1α,25-dihydroxy vitamin D3 (calcitriol).
- 42. A method for preparing a compound of Formula I comprising reacting a compound according to claim 14, with a compound of Formula III, or a salt hydrate of solvate thereof:
- 43. The method according to claim 41, wherein the amine is pyridine.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit under 35 USC §119(e) from U.S. provisional patent application S. No. 60/328,428, filed Oct. 12, 2001, the contents of which are incorporated herein by reference in their entirety.
Government Interests
[0002] This invention was made with government support under NIH Grant Number CA 44530. The government has certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60328428 |
Oct 2001 |
US |