Claims
- 1. A compound having the formula:
- 2. The compound of claim 1, wherein R1 and R3 are selected independently from the group consisting of optionally substituted cycloalkyl, cycloheteroalkyl, (cycloalkyl)alkyl, and (cycloheteroalkyl)alkyl.
- 3. The compound of claim 1, wherein R1 and R3 are selected independently from the group consisting of optionally substituted aryl, heteroaryl, aralkyl, and heteroaralkyl.
- 4. The compound of claim 3, wherein R1 and R3 are selected independently from the group consisting of optionally substituted heteroaryl and heteroaralkyl.
- 5. The compound of claim 3, wherein R1 and R3 are selected independently from the group consisting of optionally substituted aryl and aralkyl.
- 6. The compound of claim 5, wherein at least one of R1 and R3 is substituted with at least one hydroxyl, alkyloxy, aryloxy, thio, alkylthio, or arylthio group.
- 7. The compound of claim 6, wherein at least one of R1 and R3 is selected independently from the group consisting of phenyl, phenyloxyloweralkyl, and phenylloweralkyl.
- 8. The compound of claim 7, wherein at least one of R1 and R3 is substituted optionally with a substituent selected from the group consisting of halogen, nitro, cyano, loweralkyl, halolowerlalkyl, loweralkyloxy, haloloweralkyloxy, carboxy, loweralkyloxycarbonyl, aryloxycarbonyl, (cycloloweralkyl)oxycarbonyl, aralkyloxycarbonyl, heteroaryloxycarbonyl, heteroaralkyloxycarbonyl, (heterocycloloweralkyl)oxycarbonyl, loweralkylsulfinyl, loweralkylsulfonyl, loweralkylthio, arylthio, loweralkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloloweralkyl)carbonyloxy, alkylsulfonylamino, (heterocycloloweralkyl)carbonyloxy, aminocarbonyl, lowerakylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, and heteroaralkylaminocarbonyl.
- 9. The compound of claim 8, wherein at least one of R1 and R3 is further substituted optionally with a substituent selected from the group consisting of halogen, nitro, cyano, loweralkyl, halolowerlalkyl, loweralkyloxy, halolowerlakyloxy, carboxy, loweralkylthio, aminocarbonyl, and loweralkylsulfinyl.
- 10. The compound of claim 1, wherein R2 is selected from the group consisting of hydrogen, halo, and optionally substituted loweralkyl, halolowerlalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, aryloxyalkyl, arylthioalkyl, arylcarbonyl, heteroarylcarbonyl, loweralkylcarbonyl, aminocarbonyl, arylaminocarbonyl, loweralkylaminocarbonyl, aralkylaminocarbonyl, (heterocycloloweralkyl)alkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, (cycloloweralkyl)aminocarbonyl, formyl, amino, loweralkylamino, and alkenyl.
- 11. The compound of claim 10, wherein R2 is selected from the group consisting of hydrogen and halo.
- 12. The compound of claim 10, wherein R2 is selected from the group consisting of optionally substituted phenyl, phenylloweralkyl, hydroxyphenyl, loweralkyloxyphenyl, haloloweralkylsulfonylloweralkyloxyphenyl, diloweralkylaminoloweralkyloxyphenyl, (cycloaminoloweralkyl)loweralkyloxyphenyl, and (heterocycloalkyl)loweralkyloxyphenyl.
- 13. The compound of claim 10, wherein R2 is selected from the group consisting of optionally substituted loweralkyl, haloloweralkyl, hydroxyalkyl, phenyloxyloweralkyl, hydroxyphenyloweralkyl, haloloweralkylsulfonylloweralkyl, and phenylthioloweralkyl.
- 14. The compound of claim 10, wherein R2 is selected from the group consisting of optionally substituted phenylcarbonyl, (heterocycloalkyl)loweralkyloxyphenylcarbonyl, hydroxyphenylcarbonyl, halophenylcarbonyl, phenylloweralkylaminocarbonyl, diloweralkylaminocarbonyl, phenylloweralkylaminocarbonyl, hydroxyphenyllowerlalylaminocarbonyl, cycloalkylaminocarbonyl, loweralkylphenylcarbonyl, haloloweralkylsulfonylloweralkyloxyphenylcarbonyl, and nitrophenylcarbonyl.
- 15. The compound of claim 14, wherein R1 and R3 are selected independently from the group consisting of optionally substituted cycloalkyl, cycloheteroalkyl, (cycloalkyl)alkyl, and (cycloheteroalkyl)alkyl.
- 16. The compound of claim 14, wherein R1 and R3 are selected independently from the group consisting of optionally substituted aryl, heteroaryl, aralkyl, and heteroaralkyl.
- 17. The compound of claim 16, wherein R1 and R3 are selected independently from the group consisting of optionally substituted aryl and aralkyl.
- 18. The compound of claim 17, wherein at least one of R1 and R3 is substituted with at least one hydroxyl or thio group.
- 19. The compound of claim 18, wherein at least one of R1 and R3 is selected independently from the group consisting of phenyl, phenyloxyloweralkyl, and phenylloweralkyl.
- 20. The compound of (claim 19, wherein at least one of R1 and R3 is substituted optionally with a substituent selected from the group consisting of halogen, loweralkyl, halolowerlalkyl, loweralkyloxy, halolowerlakyloxy, carboxy, loweralkyloxycarbonyl, aryloxycarbonyl, (cycloloweralkyl)oxycarbonyl, aralkyloxycarbonyl, heteroaryloxycarbonyl, heteroaralkyloxycarbonyl, (heterocycloloweralkyl)oxycarbonyl, loweralkylsulfinyl, loweralkylsulfonyl, loweralkylthio, arylthio, loweralkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloloweralkyl)carbonyloxy, (heterocycloloweralkyl)carbonyloxy, aminocarbonyl, loweraklylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, and heteroaralkylaminocarbonyl.
- 21. A compound having the formula:
- 22. The compound of claim 21, wherein n is 1 and X10 is selected from the group consisting of nitrogen, optionally substituted nitrogen, and optionally substituted methylene or methine.
- 23. The compound of claim 22, wherein R4 is selected from the group consisting of optionally substituted aryl, heteroaryl, aralkyl, and heteroaralkyl.
- 24. The compound of claim 23, wherein R4 is optionally substituted aryl or aralkyl.
- 25. The compound of claim 24, wherein R4 includes at least one hydroxyl, thio, or optionally substituted loweralkyloxy, aryloxy, heteroaryloxy, loweralkylthio, arylthio, heteroarylthio, loweralkylcarbonyl, arylcarbonyl, or heteroarylcarbonyl moiety.
- 26. The compound of claim 25, wherein R4 is selected from the group consisting of phenyl, phenyloxyloweralkyl, and phenylloweralkyl.
- 27. The compound of claim 26, wherein R4 is further substituted optionally with a moiety selected from the group consisting of halogen, loweralkyl, halolowerlalkyl, loweralkyloxy, halolowerlakyloxy, carboxy, loweralkyloxycarbonyl, aryloxycarbonyl, (cycloloweralkyl)oxycarbonyl, aralkyloxycarbonyl, heteroaryloxycarbonyl, heteroaralkyloxycarbonyl, (heterocycloloweralkyl)oxycarbonyl, loweralkylsulfinyl, loweralkylsulfonyl, loweralkylthio, arylthio, loweralkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloloweralkyl)carbonyloxy, (heterocycloloweralkyl)carbonyloxy, aminocarbonyl, loweraklylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, cyano, nitro, amino, loweralkylamino, and heteroaralkylaminocarbonyl.
- 28. The compound of claim 21 wherein n is 2 and each X10 is selected independently from the group consisting of nitrogen, optionally substituted nitrogen, optionally substituted methylene, and optionally substituted methine.
- 29. The compound of claim 28, wherein R4 is selected from the group consisting of optionally substituted aryl, heteroaryl, aralkyl, and heteroaralkyl.
- 30. The compound of claim 29, wherein R4 is optionally substituted aryl or aralkyl.
- 31. The compound of claim 30, wherein R4 includes at least one hydroxyl, thio, or optionally substituted loweralkyloxy, aryloxy, heteroaryloxy, loweralkylthio, arylthio, heteroarylthio, loweralkylcarbonyl, arylcarbonyl, or heteroarylcarbonyl moiety.
- 32. The compound of claim 31, wherein R4 is selected from the group consisting of phenyl, phenyloxyloweralkyl, and phenylloweralkyl.
- 33. The compound of claim 32, wherein R4 is further substituted optionally with a moiety selected from the group consisting of halogen, loweralkyl, halolowerlalkyl, loweralkyloxy, halolowerlakyloxy, carboxy, loweralkyloxycarbonyl, aryloxycarbonyl, (cycloloweralkyl)oxycarbonyl, aralkyloxycarbonyl, heteroaryloxycarbonyl, heteroaralkyloxycarbonyl, (heterocycloloweralkyl)oxycarbonyl, loweralkylsulfinyl, loweralkylsulfonyl, loweralkylthio, arylthio, loweralkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloloweralkyl)carbonyloxy, (heterocycloloweralkyl)carbonyloxy, aminocarbonyl, loweraklylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, cyano, nitro, amino, loweralkylamino, and heteroaralkylaminocarbonyl.
- 34. The compound of claim 21, wherein X6-X9 are selected independently from the group consisting of nitrogen and optionally substituted methine.
- 35. The compound of claim 34, wherein at least one of X6-X9 is methine substituted with a moiety selected from the group consisting of loweralkyloxy, aryloxy, heteroaryloxy, loweralkylthio, arylthio, heteroarylthio, loweralkylcarbonyl, arylcarbonyl, and heteroarylcarbonyl.
- 36. The compound of claim 35, wherein X7 is methine substituted with hydroxy or loweralkyloxy.
- 37. The compound of claim 34, wherein n is 1 and X10 is selected from the group consisting of nitrogen, optionally substituted nitrogen, and optionally substituted methylene or methine.
- 38. The compound of claim 37, wherein R4 is selected from the group consisting of optionally substituted aryl, heteroaryl, aralkyl, and heteroaralkyl.
- 39. The compound of claim 38, wherein R4 is optionally substituted aryl or aralkyl.
- 40. The compound of claim 39, wherein R4 includes at least one hydroxyl, thio, or optionally substituted loweralkyloxy, aryloxy, heteroaryloxy, loweralkylthio, arylthio, heteroarylthio, loweralkylcarbonyl, arylcarbonyl, or heteroarylcarbonyl moiety.
- 41. The compound of claim 40, wherein R4 is selected from the group consisting of phenyl, phenyloxyloweralkyl, and phenylloweralkyl.
- 42. The compound of claim 41, wherein R4 is further substituted optionally with a moiety selected from the group consisting of halogen, loweralkyl, halolowerlalkyl, loweralkyloxy, halolowerlakyloxy, carboxy, loweralkyloxycarbonyl, aryloxycarbonyl, (cycloloweralkyl)oxycarbonyl, aralkyloxycarbonyl, heteroaryloxycarbonyl, heteroaralkyloxycarbonyl, (heterocycloloweralkyl)oxycarbonyl, loweralkylsulfinyl, loweralkylsulfonyl, loweralkylthio, arylthio, loweralkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloloweralkyl)carbonyloxy, (heterocycloloweralkyl)carbonyloxy, aminocarbonyl, loweraklylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, cyano, nitro, amino, loweralkylamino, and heteroaralkylaminocarbonyl.
- 43. The compound of claim 34, wherein n is 2 and each X10 is selected independently from the group consisting of nitrogen, optionally substituted nitrogen, optionally substituted methylene, and optionally substituted methine.
- 44. The compound of claim 43, wherein R4 is selected from the group consisting of optionally substituted aryl, heteroaryl, aralkyl, and heteroaralkyl.
- 45. The compound of claim 44, wherein R4 is optionally substituted aryl or aralkyl.
- 46. The compound of claim 45, wherein R4 includes at least one hydroxyl, thio, or optionally substituted loweralkyloxy, aryloxy, heteroaryloxy, loweralkylthio, arylthio, heteroarylthio, loweralkylcarbonyl, arylcarbonyl, or heteroarylcarbonyl moiety.
- 47. The compound of claim 46, wherein R4 is selected from the group consisting of phenyl, phenyloxyloweralkyl, and phenylloweralkyl.
- 48. The compound of claim 47, wherein R4 is further substituted optionally with a moiety selected from the group consisting of halogen, loweralkyl, halolowerlalkyl, loweralkyloxy, halolowerlakyloxy, carboxy, loweralkyloxycarbonyl, aryloxycarbonyl, (cycloloweralkyl)oxycarbonyl, aralkyloxycarbonyl, heteroaryloxycarbonyl, heteroaralkyloxycarbonyl, (heterocycloloweralkyl)oxycarbonyl, loweralkylsulfinyl, loweralkylsulfonyl, loweralkylthio, arylthio, loweralkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloloweralkyl)carbonyloxy, (heterocycloloweralkyl)carbonyloxy, aminocarbonyl, loweraklylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, cyano, nitro, amino, loweralkylamino, and heteroaralkylaminocarbonyl.
- 49. A composition for use in treating an estrogen receptor-mediated disorder in a mammal, comprising a therapeutically effective amount of a compound of claim 1 in a pharmaceutically effective carrier.
- 50. A composition for use in treating an estrogen receptor-mediated disorder in a mammal, comprising a therapeutically effective amount of a compound of claim 21 in a pharmaceutically effective carrier.
- 51. A method for treating an estrogen receptor-mediated disorder in a mammal, comprising administering to such mammal a therapeutically effective amount of a compound of claim 1 in a pharmaceutically effective carrier.
- 52. The method of claim 51, wherein said disease is chosen from the group consisting of: osteoporosis, estrogen-dependent cancer, Alzheimer's disease, and estrogen-dependent illness.
- 53. A method for treating an estrogen receptor-mediated disorder in a mammal, comprising administering to such mammal a therapeutically effective amount of a compound of claim 21 in a pharmaceutically effective carrier.
- 54. The method of claim 53, wherein said disease is chosen from the group consisting of: osteoporosis, estrogen-dependent cancer, and estrogen-dependent illness.
- 55. A method for preventing an estrogen receptor-mediated disorder in a mammal, comprising administering to such mammal a prophylactically effective amount of a compound of claim 1 in a pharmaceutically effective carrier.
- 56. The method of claim 55, wherein said disease is chosen from the group consisting of: osteoporosis, estrogen-dependent cancer, Alzheimer's disease and estrogen-dependent illness.
- 57. A method for preventing an estrogen receptor-mediated disorder in a mammal, comprising administering to such mammal a prophylactically effective amount of a compound of claim 21 in a pharmaceutically effective carrier.
- 58. The method of claim 57, wherein said disease is chosen from the group consisting of: osteoporosis, estrogen-dependent cancer, aid estrogen-dependent illness.
- 59. A method for modulating the biological activity of an estrogen receptor, comprising exposing said estrogen receptor to a compound of claim 1 to modulate thereby the binding of said estrogen receptor to an associated estrogen receptor element.
- 60. The method of claim 59, wherein said estrogen receptor is the α isoform.
- 61. The method of claim 59, wherein said estrogen receptor is the β isoform.
- 62. A method for modulating the biological activity of an estrogen receptor, comprising exposing said estrogen receptor to a compound of claim 21 to modulate thereby the binding of said estrogen receptor to an associated estrogen receptor element.
- 63. The method of claim 62, wherein said estrogen receptor is the α isoform.
- 64. The method of claim 62, wherein said estrogen receptor is the β isoform.
1 CROSS REFERENCE TO RELATED U.S. PATENT APPLICATIONS
[0001] The present application claims priority under 35 U.S.C. § 119(e) from co-pending provisional U.S. patent application serial No. 60/095,773, which is incorporated herein by reference in its entirety and for all purposes.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60095773 |
Aug 1998 |
US |
Continuations (1)
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Number |
Date |
Country |
Parent |
09833392 |
Apr 2001 |
US |
Child |
10134302 |
Apr 2002 |
US |