Claims for Patent: 5,998,402

Summary for Patent: 5,998,402

Title:	2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents
Abstract:	The present invention relates to new 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds which are useful as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utilizing these compounds, which have the general structures below:
Inventor(s):	Chris P. Miller, Michael D. Collini, Bach D. Tran, Arthur A. Santilli
Assignee:	Wyeth LLC
Application Number:	US08/833,271
Patent Claims:	1. A compound selected from the formulas I or II: ##STR180## wherein: R1 is selected from H, OH, -O-C(O)-C1 -C12 alkyl (straight chain or branched), -O-C1 -C12 alkyl (straight chain or branched or cyclic), or halogens; or C1 -C4 halogenated ethers,R2, R3, R4, R5, and R6 are independently selected from H, OH, -O-C(O)-C1 -C12 (straight chain or branched), -O-C1 -C12 (straight chain or branched or cyclic), halogens, or C1 -C4 halogenated ethers, cyano, C1 -C6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; X is selected from H, C1 -C6 alkyl, cyano, nitro, trifluoromethyl, halogen; n is 2or 3; Y is the moiety: ##STR181## wherein: a) R7 and R8 are independently selected from the group of H, C1 -C6 alkyl, or phenyl optionally substituted by CN, C1 -C6 alkyl (straight chain or branched), C1 -C6 alkoxy (straight chain or branched), halogen, -OH, -CF3, or -OCF3 ; or b) R7 and R8 are concatenated to form a five-membered saturated heterocycle containing one nitrogen heteroatom, the heterocycle being optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN-, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, -NO2, or phenyl optionally substituted with 1-3 (C1 -C4)alkyl; or c) R7 and R8 are concatenated to form a six-membered saturated heterocycle containing one nitrogen heteroatom, the heterocycle being optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, -NO2, or phenyl optionally substituted with 1-3 (C1 -C4)alkyl; or d) R7 and R8 are concatenated to form a seven-membered saturated heterocycle containing one nitrogen heteroatom, the heterocycle being optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, -NO2, or phenyl optionally substituted with 1-3 (C1 -C4)alkyl; or e) R7 and R8 are concatenated to form an eight-membered saturated heterocycle containing one nitrogen heteroatom, the heterocycle being optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, -NO2, or phenyl optionally substituted with 1-3 (C1 -C4)alkyl; or f) R7 and R8 are concatenated to form a saturated bicyclic heterocycle containing from 6-12 carbon atoms either bridged or fused and containing one nitrogen heteroatom, the heterocycle being optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, -NO2, or phenyl optionally substituted with 1-3 (C1 -C4) alkyl;or a pharmaceutically acceptable salt thereof. 2. A compound of claim 1 wherein:R1 is selected from H, OH, -O-C(O)-C1 -C4 alkyl or -O-C1 -C4 alkyl, halogen; R2, R3, R4, R5, and R6 are independently selected from H, OH , -O-C(O)-(C1 -C4 alkyl), -O-(C1 -C4 alkyl), halogen, cyano, C1 -C6 alkyl, or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; X is selected from H, C1 -C6 alkyl, cyano, nitro, triflouromethyl, halogen; Y is the moiety ##STR182## R7 and R8 are selected independently from H, C1 -C6 alkyl, or combined by -(CH2)p-, wherein p is an integer of from 2 to 6, so as to form a saturated ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONH(C1 -C4), -NH2, C1 -C4 alkylamino, di(C1 -C4)alkylamino, -NHSO2 (C1 -C4), -NHCO(C1 -C4), or -NO2 ;or a pharmaceutically acceptable salt thereof. 3. A compound selected from the formulas I or II: ##STR183## wherein: R1 is selected from H, OH, -O-C(O)-C1 -C12 alkyl (straight chain or branched), -O-C1 -C12 alkyl (straight chain or branched or cyclic), or halogens; or C1 -C4 halogenated ethers.R2, R3, R4, R5, and R6 are independently selected from H, OH, -O-C(O)-C1 -C12 (straight chain or branched), -O-C1 -C12 (straight chain or branched or cyclic), halogens, or C1 -C4 halogenated ethers, cyano, C1 -C6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; X is selected from H, C1 -C6 alkyl, cyano, nitro, trifluoromethyl, halogen; n is 2 or 3; Y is the moiety: ##STR184## wherein: a) R7 and R8 are independently selected from the group of H, C1 -C6 alkyl, or phenyl optionally substituted by CN, C1 -C6 alkyl (straight chain or branched), C1 -C6 alkoxy (straight chain or branched), halogen, -OH, -CF3, or -OCF3 ; or b) R7 and R8 are concatenated to form a pyrrolidine ring, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN-, -CONHR1,-NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, or -NO2 ; or c) R7 and R8 are concatenated to form a piperidine ring, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1,-NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, or -NO2 ; or d) R7 and R8 are concatenated to form an azepan ring, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, or -NO2 ; or e) R7 and R8 are concatenated to form a bicyclic heterocycle containing from 6-12 carbon atoms either bridged or fused and containing one nitrogen heteroatom, the heterocycle being optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 acyloxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2, -NHSO2 R1, -NHCOR1, or -NO2 ;or a pharmaceutically acceptable salt thereof. 4. A compound selected from the formulas I or II: ##STR185## wherein: R1 is selected from H, OH, -O-C(O)-(C1 -C4 alkyl), -O-(C1 -C4 alkyl), halogen, or C1 -C4 halogenated ethers;R2, R3, R4, R5, and R6 are independently selected from H, OH, -O-C(O)-(C1 -C4 alkyl), -O-(C1 -C4 alkyl), halogen, or C1 -C4 halogenated ethers, cyano, C1 -C6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; X is selected from H, C1 -C6 alkyl, cyano, nitro, trifluoromethyl, halogen; n is 2or 3; Y is the moiety: ##STR186## wherein R7 and R8 are independently selected from the group of H, C1 -C6 alkyl, or phenyl optionally substituted by CN, C1 -C6 alkyl (straight chain or branched), C1 -C6 alkoxy (straight chain or branched), halogen, -OH, -CF3, or -OCF3 ; or R7 and R8 are concatenated to form a nitrogen containing heterocyclic moiety selected from the group of: ##STR187## the nitrogen containing heterocyclic moiety being optionally substituted by from 1 to 3 groups selected from hydrogen, hydroxy, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 alkylthio, -CN, -CO2 H, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2 or -NO2 ;or a pharmaceutically acceptable salt thereof. 5. A compound of claim 4 wherein R1 is selected from H, OH, -O-C(O)-(C1 -C4 alkyl), -O-(C1 -C4 alkyl), halogen, or C1 -C4 halogenated ethers;R2, R3, R4, R5, and R6 are independently selected from H, OH, -O-C(O)-(C1 -C4 alkyl), -O-(C1 -C4 alkyl), halogen, or C1 -C4 halogenated ethers, cyano, C1 -C6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; X is selected from H, C1 -C6 alkyl, cyano, nitro, trifluoromethyl, halogen; n is 2or 3; Y is the moiety: ##STR188## wherein R7 and R8 are independently selected from the group of H or C1 -C6 alkyl; or R7 and R8 are concatenated to form a nitrogen containing heterocyclic moiety of the group: ##STR189## the nitrogen containing heterocyclic moiety being optionally substituted by from 1 to 3 groups selected from hydrogen, hydroxy, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 alkylthio, -CN, -CO2 H, -CONHR1, -NH2, -NH(C1 -C4 alkyl), -N(C1 -C4 alkyl)2 or -NO2 ;or a pharmaceutically acceptable salt thereof. 6. A compound of claim 1 which is 5-Benzyloxy-2-(4-ethoxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 7. A compound of claim 1 which is 5-Benzyloxy-2-phenyl-3-methyl-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 8. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 9. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[4-(2-diisopropylamino-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 10. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[4-(2-butyl-methylamino-1-ylethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 11. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-{4-dimethylamino)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 12. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-{4-[2-(2-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 13. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-{4-[2-(3-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 14. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-{4-[2-(4-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 15. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-{4-[2-((cis)-2,6-Dimethyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 16. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-{4-[2-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 17. A compound of claim 1 which is (1S, 4R)-5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl{4-[2-(2-Aza-bicyclo[2.2.1]hept-2-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 18. A compound of claim 1 which is 5-Benzyloxy-2-(4-flouro-phenyl)-3-methyl-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 19. A compound of claim 1 which is 5-Benzyloxy-2-(4-flouro-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 20. A compound of claim 1 which is 5-Benzyloxy-2-(4-chloro-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 21. A compound of claim 1 which is 5-Benzyloxy-2-[3,4 methylenedioxy-phenyl]-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 22. A compound of claim 1 which is 5-Benzyloxy-2-[4isopropoxy-phenyl]-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 23. A compound of claim 1 which is 5-Benzyloxy-2-[4 methyl-phenyl]-3-methyl-1-[4(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 24. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-benzyloxy-2-(3-benzyloxy-phenyl)-3-methyl-1H-indole or a pharmaceutically acceptable salt thereof. 25. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-3-fluoro-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 26. A compound of claim 1 which is 5-Benzyloxy-2-(4benzyloxy-3-fluoro-phenyl)-3-methyl-1-[4(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 27. A compound of claim 1 which is 5-Benzyloxy-2-(3-methoxy-phenyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-3-methyl-1H-indole or a pharmaceutically acceptable salt thereof. 28. A compound of claim 1 which is 5-Benzyloxy-3-methyl-1-[4(2-piperidin-1-yl-ethoxy)-benzyl]-2-(4-trifluoromethoxy-phenyl)-1H-indole or a pharmaceutically acceptable salt thereof. 29. A compound of claim 1 which is (2-{4-[5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-indol-1-ylmethyl]-phenoxy}-ethyl)-cyclohexyl-amine or a pharmaceutically acceptable salt thereof. 30. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-{4-methylpiperazin-1-yl)-ethoxy]-benzyl}-1H-indole or a pharmaceutically acceptable salt thereof. 31. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-benzyloxy-2-(3-methoxy-phenyl)-3-methyl-1H-indole or a pharmaceutically acceptable salt thereof. 32. A compound of claim 1 which is 4-{3-Methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole} (HCl). 33. A compound of claim 1 which is 4-{3-Methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-2-yl}-phenol hydrochloride (HCl). 34. A compound of claim 1 which is 3-Methyl-2-phenyl-1-[4-(2-piperidine-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 35. A compound of claim 1 which is 4-{5-Methoxy-3-methyl-1-{4-[2-(piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-2-yl}-phenol or a pharmaceutically acceptable salt thereof. 36. A compound of claim 1 which is 2-(4-methoxy-phenyl)-3-methyl-1-{4-[2-(piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 37. A compound of claim 1 which is 5-Methoxy-2-(4-methoxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole (HCI). 38. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-methoxy-2-(4-methoxy-phenyl)-3-methyl-1H-indole (HCI). 39. A compound of claim 1 which is 2-(4-Ethoxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 40. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-ethoxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 41. A compound of claim 1 which is 4-{5-Fluoro-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-2-yl}-phenol (HCl). 42. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-3-methyl-2-phenyl-1H-indol-5-ol (HCl). 43. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-[4-(2-pyrollidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 44. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol (HCl). 45. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol Acetate Salt. 46. A compound of claim 1 which is 1-[4-(2-Azocan-1-yl-ethoxy)-benzyl]-2-(4 hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 47. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-[4-(2-dimethyl-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 48. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-[4-(2-diethyl-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 49. A compound of claim 1 which is 1-[4-(2-Dipropylamino-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 50. A compound of claim 1 which is 1-[4-(2-Dibutylamino-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 51. A compound of claim 1 which is 1-[4-(2-Diisopropylamino-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 52. A compound of claim 1 which is 1-{4-[2-(Butyl-methyl-amino)-ethoxy]-benzyl}-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 53. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-{4-[2-(2-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 54. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-{4-[2-(3-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 55. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-{4-[2-(4-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-5-ol (HCl). 56. A compound of claim 1 which is 1-{4-[2-(3,3-Dimethyl-piperidin-1-yl)-ethoxy]-benzyl}-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 57. A compound of claim 1 which is 1-{4-[2-((cis)-2,6-Dimethyl-piperidin-1-yl)-ethoxy]-benzyl}-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 58. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-1-{4-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-benzyl}-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 59. A compound of claim 1 which is (1S, 4R)-1-{4-[2-(2-Aza-bicyclo [2.2.1]hept-2-yl)-ethoxy]-benzyl}-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 60. A compound of claim 1 which is 2-(4Hydroxy-phenyl)-3-methyl-1-({4-[2-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-ethoxy]-benzyl}-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 61. A compound of claim 1 which is 2-(4-Fluoro-phenyl)-3-methyl-1-[4-(2-piperidine-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 62. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-fluoro-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 63. A compound of claim 1 which is 2-(3-Methoxy-4-hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 64. A compound of claim 1 which is 2-Benzo[1,3]dioxol-5-yl-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCI). 65. A compound of claim 1 which is 2-(4-Isopropoxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 66. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-isopropoxy-phenyl)-3-methyl-1H-indol-5-ol (HCl). 67. A compound of claim 1 which is 2-(4-Cyclopenyloxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 68. A compound of claim 1 which is 3-Methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-2-(4-trifluoromethyl-phenyl)-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 69. A compound of claim 1 which is 3-Methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-2-p-tolyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 70. A compound of claim 1 which is 2-(4-Chloro-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCI). 71. A compound of claim 1 which is 2-(2,4-Dimethoxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 72. A compound of claim 1 which is 2-(3-Hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 73. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(3-hydroxy-phenyl)-3-methyl-1H-indole-5-ol or a pharmaceutically acceptable salt thereof. 74. A compound of claim 1 which is 2-(3-Fluoro-4-hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 75. A compound of claim 1 which is 2-(3-Fluoro-4-hydroxy-phenyl)-3-methyl-1-[4-(azepan-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 76. A compound of claim 1 which is 2-(3-Methoxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole-5-ol or a pharmaceutically acceptable salt thereof. 77. A compound of claim 1 which is 3-Methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-2-(4-trifluoromethoxy-phenyl)-1H-indole-5-ol or a pharmaceutically acceptable salt thereof. 78. A compound of claim 1 which is 3-Chloro-2-(4-hydroxy-phenyl)-1-[4-(2-pyrrolidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 79. A compound of claim 1 which is 3-Chloro-2-(4-hydroxy-phenyl)-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 80. A compound of claim 1 which is 3-Chloro-2-(4-hydroxy-phenyl)-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 81. A compound of claim 1 which is 3-Chloro-2-(4-hydroxy-2-methyl-phenyl)-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 82. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-ethyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl). 83. A compound of claim 1 which is 5-Hydroxy-2-(4-Hydroxy-phenyl)-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole-3-carbonitrile (HCl). 84. A compound of claim 1 which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-hydroxy-2-(4-hydroxy-phenyl)-1H-indole-3-cabonitrile (HCl). 85. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-chloro-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 86. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-chloro-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 87. A compound of claim 1 which is 5-Benzyloxy-2-(2-methyl-4-benzyloxy-phenyl)-3-chloro-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 88. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-ethyl-1-[4-(2-piperidin -1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 89. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-cyano-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 90. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-cyano-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 91. A compound of claim 1 which is Di-propionate of 1-[4(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol. 92. A compound of claim 1 which is Di-pivalate of 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol. 93. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-3-methyl-1H-indole or a pharmaceutically acceptable salt thereof. 94. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-{4-[3-(piperidin-1-yl)-propoxy]-benzyl}-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 95. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-1-[3-methoxy-4-(2-piperidin-1-yl-ethoxy)-benzyl]-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 96. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-1-[3-methoxy-4(2-azepan-1-yl-ethoxy)-benzyl]-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 97. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[3-Methoxy-4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 98. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[2-Methoxy-4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 99. A compound of claim 1 which is Di-pivalate ester of 2-(4-Hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol. 100. A compound of claim 1 which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[4(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 101. A compound of claim 1 which is 5-Benzyloxy-2-(3-benzyloxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof. 102. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-[4 (2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof. 103. A compound of claim 1 which is 2-(4-Hydroxy-phenyl)-3-methyl-1-[4 (2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol methiodide. 104. A compound of claim 1 which is 2-(4Hydroxy-phenyl)-3-methyl-1-[4 (2-dimethyl-1-yl-ethoxy)-benzyl]-1H-indol-5-ol methiodide. 105. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. 106. A method of treating or preventing bone loss in a mammal, the method comprising administering to a mammal in need thereof an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 107. A compound of claim 1 wherein:R1 is OH; R2, R3, R4, R5, and R6 are independently selected from H, OH or the C1 -C4 esters or alkyl ethers thereof, halogen, cyano, C1 -C6 alkyl, or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; X is selected from the group of Cl, NO2, CN, CF3, or CH3 ; Y is the moiety ##STR190## R7 and R8 are concatenated together as -(CH2)r -, wherein r is an integer of from 4 to 6, to form a ring optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C1 -C4 alkyl, trihalomethyl, C1 -C4 alkoxy, trihalomethoxy, C1 -C4 alkylthio, C1 -C4 alkylsulfinyl, C1 -C4 alkylsulfonyl, hydroxy (C1 -C4)alkyl, -CO2 H, -CN, -CONH(C1 -C4), -NH2, C1 -C4 alkylamino, di(C1 -C4)alkylamino, -NHSO2 (C1 -C4), -NHCO(C1 -C4), and -NO2 ; or a pharmaceutically acceptable salt thereof.