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 is selected from the group consisting of OH, OCH3 and fluoro.
- 3. The compound according to claim 2, wherein R1 is OH.
- 4. The compound according to claim 1, wherein R2 is selected from the group consisting of H, OH, OCH3 and fluoro.
- 5. The compound according to claim 4, wherein R2 is selected from the group consisting of H, OH and fluoro.
- 6. The compound according to claim 5, wherein R2 is selected from the group consisting of H and OH.
- 7. The compound according to claim 1, wherein R1 and R2 are both OH.
- 8. The compound according to claim 1, wherein each R3 together form ═CH2.
- 9. The compound according to claim 1, wherein each R3 is H.
- 10. The compound according to claim 1, wherein R4 is CH3.
- 11. The compound according to claim 1, wherein each R5 is selected from the group consisting of F, C1-4alkyl and H or are taken together to form a C3-5cycloalkyl ring.
- 12. The compound according to claim 11, wherein each R5 is selected from the group consisting of F, CH3 and H or are taken together to form a C3-4cycloalkyl ring.
- 13. The compound according to claim 12, wherein both of R5 are CH3, F or H or are taken together to form a cyclopropyl ring.
- 14. The compound according to claim 13, wherein each R5 is H.
- 15. The compound according to claim 13, wherein each R5 are taken together to form a cyclopropyl ring.
- 16. The compound according to claim 1, wherein R6 is selected from the group consisting of C1-4alkyl, C3scycloalkyl, aryl and heteroaryl, wherein each of C1-4alkyl, C3-5cycloalkyl, aryl and heteroaryl are either unsubstituted or substituted with 1-3 substituents independently selected from the group consisting of C1-4alkyl, OC1-4alkyl, CF3, NO2 and halo.
- 17. The compound according to claim 16, wherein R6 is selected from the group consisting of C1-4alkyl, C3-5cycloalkyl, aryl and heteroaryl, wherein each of C1-4alkyl, C3-5cycloalkyl, aryl and heteroaryl are either unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of C1-4alkyl, OC1-4alkyl, CF3, NO2 and halo.
- 18. The compound according to claim 17, wherein R6 is selected from the group consisting of C1-4alkyl and aryl, wherein aryl is either unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of C1-4alkyl, OC1-4alkyl, CF3, NO2 and halo.
- 19. The compound according to claim 18, wherein R6 is selected from the group consisting of C1-4alkyl and phenyl, wherein phenyl is either unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of C1-4alkyl, OC1-4alkyl, CF3, NO2 and halo.
- 20. The compound according to claim 19, wherein R6 is a phenyl group either unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of CH3, OCH3, NO2, F and Cl.
- 21. The compound according to claim 20, wherein R6 is an unsubstituted phenyl or phenyl substituted with 1 substituent independently selected from the group consisting of CH3, OCH3, NO2, F and Cl.
- 22. The compound according to claim 20, wherein R6 is t-butyl.
- 23. The compound according to claim 1, wherein R7 is selected from the group consisting of C1-4alkyl and H.
- 24. The compound according to claim 23, wherein R7 is selected from CH3 or H.
- 25. The compound according to claim 1, wherein R7 is C(O)R8.
- 26. The compound according to claim 25, wherein R8 is selected from the group consisting of C1-4alkyl, C3-5cycloalkyl, aryl-C1-2alkyl, aryl and heteroaryl, wherein each of C1-4alkyl, C3-5cycloalkyl, aryl and heteroaryl are either unsubstituted or substituted with 1-3 substituents independently selected from the group consisting of C1-4alkyl, OCI 4alkyl, CF3, NO2 and halo.
- 27. The compound according to claim 26, wherein R8 is selected from the group consisting of C1-4alkyl, C3-5cycloalkyl, PhCH2 and phenyl, wherein each of C1-4alkyl, C3-5cycloalkyl, PhCH2 and phenyl are either unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of C1-4alkyl, OC1-4alkyl, CF3, NO2, F and Cl.
- 28. The compound according to claim 26, wherein R8 is selected from the group consisting of C1-4alkyl, PhCH2 and phenyl, wherein each of C1-4alkyl, PhCH2 and phenyl are either unsubstituted or substituted with I substituent independently selected from the group consisting of C1-4alkyl, OC1-4alkyl, CF3, NO2, F and Cl.
- 29. The compound according to claim 1, wherein R6 is C1-6alkyl and between C16 and C17 is a double bond.
- 30. The compound according to claim 1, wherein between C22-C23 represents a single bond.
- 31. The compound according to claim 1, wherein between C16-C17 represents a single bond.
- 32. The compound according to claim 1, wherein both represents a single bond.
- 33. The compound according to claim 1, having the following relative stereochemistry:
- 34. The compound according to claim 31, having the following relative stereochemistry:
- 35. The compound according to claim 1, having the following relative stereochemistry:
- 36. The compound according to claim 1 that is selected from the group consisting of:
- 37. The compound according to claim 36, selected from the group consisting of I(a); I(c); I(e); I(g); I(i); I(j); I(l); 1(m); I(n); I(o); I(p) and I(q).
- 38. The compound according to claim 37, selected from the group consisting of I(a), I(c), I(e), I(g), I(i), I(j), I(l), I(n) I(o) and I(p).
- 39. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
- 40. A method for treating diseases which benefit from a modulation of the levels of 1α,25-dihydroxy vitamin D3, or analogs thereof, comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 41. A method for treating diseases which benefit from an increase in the levels of 1α,25-dihydroxy vitamin D3, or analogs thereof, comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 42. A method for treating diseases which benefit from an inhibition of the catabolism of 1α,25-dihydroxy vitamin D3, or analogs thereof, comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 43. The method according to claim 42, wherein the disease is selected from the group consisting of cancer, dermatological disorders, parathyroid disorders, autoimmune disorders and bone disorders.
- 44. The method according to claim 43, wherein the disease is selected from the group consisting of cancer, psoriasis, hyperparathyroidism, secondary hyperparathyroidism and osteoporosis.
- 45. A method of inhibiting cell proliferation and/or for promoting cell differentiation comprising administering an effective amount of a compound according to claim 1 to a cell or animal in need thereof.
- 46. The method according to claim 45, wherein the cell is a cancer cell.
- 47. The method according to claim 46, wherein the cancer is selected from breast cancer, lung cancer, prostate cancer, colon cancer, colorectal cancer, kidney cancer, head and neck cancer, pancreatic cancer, Kaposi's sarcoma and leukemia.
- 48. The method according to claim 45, wherein the cell is a skin cell.
- 49. The method according to claim 48, wherein the cell is a keratinocyte.
- 50. A method of inhibiting CYP24 activity in a cell by administering an effective amount of a compound according to claim 1 to the cell.
- 51. A method of treating a disease which benefits from an inhibition of CYP24 activity comprising administering an effective amount of a compound according to claim 1 to an animal or cell in need thereof.
- 52. A use of a compound according to claim 1 to treat a disease which benefits from a modulation in the levels of 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 53. A use of a compound according to claim 1 to treat a disease which benefits from an increase in the levels of 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 54. A use of a compound according to claim 1 to treat a disease which benefits from an inhibition of the catabolism of 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 55. A use of a compound according to claim 1 to prepare a medicament to treat a disease which benefits from an modulation of the levels of 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 56. A use of a compound according to claim 1 to prepare a medicament to treat a disease which benefits from an increase in the levels of 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 57. A use of a compound according to claim 1 to prepare a medicament to treat a disease which benefits from an inhibition of the catabolism of 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 58. A use of a compound according to claim 1 to inhibit cell proliferation and/or promote cell differentiation.
- 59. A use of a compound according to claim 1 to prepare a medicament to inhibit cell proliferation and/or promote cell differentiation.
- 60. A use of a compound according to claim 1 to inhibit CYP24 activity.
- 61. A use of a compound according to claim 1 to prepare a medicament to inhibit CYP24 activity.
- 62. 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 a vitamin D receptor agonist to an animal or cell in need thereof.
- 63. A method of treating diseases comprising co-administering an effective amount of a compound according to claim 1 and an effective amount of a vitamin D receptor agonist to an animal or cell in need thereof.
- 64. The method according to claim 63, wherein the vitamin D receptor agonist is 1α,25-dihydroxy vitamin D3 (calcitriol), or an analog thereof.
- 65. The method according to claim 64, wherein the compound is selected from the group consisting of I(a), I(c), I(e), I(g), I(i), I(j), I(l), I(n) and I(o).
- 66. The method according to claim 65, wherein the disease is selected from the group consisting of cancer, dermatological disorders, parathyroid disorders, autoimmune disorders and bone disorders.
- 67. The method according to claim 66, wherein the disease is selected from the group consisting of cancer, psoriasis, hyperparathyroidism, secondary hyperparathyroidism and osteoporosis.
- 68. The method according to claim 67, wherein the disease is cancer.
- 69. The method according to claim 68, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, prostate cancer, colon cancer, colorectal cancer, kidney cancer, head and neck cancer, pancreatic cancer, Kaposi's sarcoma and leukemia.
- 70. A use of a compound according claim 1 to increase the efficacy of a vitamin D receptor agonist.
- 71. A use of a compound according to claim 1 to prepare a medicament to increase the efficacy of a vitamin D receptor agonist.
- 72. A use of a compound according to claim 1 and a vitamin D receptor agonist to treat a disease which benefits from co-administering an effective amount of a compound according to any one of claims 1-38 and an effective amount of a vitamin D receptor agonist.
- 73. A use of a compound according to claim 1 to prepare a medicament to treat a disease which benefits from co-administering an effective amount of a compound according to any one of claims 1-38 and an effective amount of a vitamin D receptor agonist.
- 74. The use according to claim 70, wherein the vitamin D receptor agonist is 1α,25-dihydroxy vitamin D3, or an analog thereof.
- 75. The use according to claim 74, wherein the compound is selected from the group consisting of I(a), I(c), I(e), I(g), I(i), I(j), I(l), I(n) and I(o).
- 76. The use according to claim 75, wherein the disease is selected from the group consisting of cancer, dermatological disorders, parathyroid disorders, autoimmune disorders and bone disorders.
- 77. The use according to claim 76, wherein the disease is selected from the group consisting of cancer, psoriasis, hyperparathyroidism, secondary hyperparathyroidism and osteoporosis.
- 78. A method of treating cancer, dermatological disorders, parathyroid disorders, autoimmune disorders or bone disorders comprising administering an effective amount of a compound according to claim 1 in combination with one or more therapies or therapeutics to treat cancer, dermatological disorders, parathyroid disorders, autoimmune disorders or bone disorders, to an animal or cell in need thereof.
- 79. A method of treating cancer comprising administering an effective amount of a compound according to claim 1 in combination with one or more therapies or therapeutics to treat cancer.
- 80. The method according to claim 79, wherein the one or more therapies or therapeutics to treat cancer are selected from the group consisting of surgery, radiation, chemotherapy and biotherapy.
- 81. A method of treating psoriasis comprising administering an effective amount of a compound according to claim 1 in combination with one or more therapies or therapeutics to treat psoriasis.
- 82. The method according to claim 81, wherein the one or more therapies or therapeutics to treat psoriasis are selected from the group consisting of ultraviolet B radiation, chemotherapy and biotherapy.
- 83. A use of a compound according to claim 1 in combination with one or more therapies or therapeutics to treat cancer, dermatological disorders, parathyroid disorders, autoimmune disorders or bone disorders.
- 84. A use of a compound according to claim 1 in combination with one or more therapies or therapeutics to treat cancer.
- 85. A use of a compound according to claim 1 in combination with one or more therapies or therapeutics to treat psoriasis.
Government Interests
[0001] This invention was made with government support under NIH Grant Number CA44530. The government has certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60387904 |
Jun 2002 |
US |