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Claims for Patent: 5,998,402

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Claims 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: ##STR1##
Inventor(s): Miller; Chris P. (Strafford, PA), Collini; Michael D. (Clifton Heights, PA), Tran; Bach D. (Media, PA), Santilli; Arthur A. (Havertown, PA)
Assignee: American Home Products Corporation (Madison, NY)
Application Number:08/833,271
Patent Claims: 1. A compound selected from the formulas I or II: ##STR180## wherein: R.sub.1 is selected from H, OH, -O-C(O)-C.sub.1 -C.sub.12 alkyl (straight chain or branched), -O-C.sub.1 -C.sub.12 alkyl (straight chain or branched or cyclic), or halogens; or C.sub.1 -C.sub.4 halogenated ethers,

R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, OH, -O-C(O)-C.sub.1 -C.sub.12 (straight chain or branched), -O-C.sub.1 -C.sub.12 (straight chain or branched or cyclic), halogens, or C.sub.1 -C.sub.4 halogenated ethers, cyano, C.sub.1 -C.sub.6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R.sub.1 is H, R.sub.2 is not OH;

X is selected from H, C.sub.1 -C.sub.6 alkyl, cyano, nitro, trifluoromethyl, halogen;

n is 2or 3;

Y is the moiety: ##STR181## wherein: a) R.sub.7 and R.sub.8 are independently selected from the group of H, C.sub.1 -C.sub.6 alkyl, or phenyl optionally substituted by CN, C.sub.1 -C.sub.6 alkyl (straight chain or branched), C.sub.1 -C.sub.6 alkoxy (straight chain or branched), halogen, -OH, -CF.sub.3, or -OCF.sub.3 ; or

b) R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN-, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, -NO.sub.2, or phenyl optionally substituted with 1-3 (C.sub.1 -C.sub.4)alkyl; or

c) R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, -NO.sub.2, or phenyl optionally substituted with 1-3 (C.sub.1 -C.sub.4)alkyl; or

d) R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, -NO.sub.2, or phenyl optionally substituted with 1-3 (C.sub.1 -C.sub.4)alkyl; or

e) R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, -NO.sub.2, or phenyl optionally substituted with 1-3 (C.sub.1 -C.sub.4)alkyl; or

f) R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, -NO.sub.2, or phenyl optionally substituted with 1-3 (C.sub.1 -C.sub.4) alkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 wherein:

R.sub.1 is selected from H, OH, -O-C(O)-C.sub.1 -C.sub.4 alkyl or -O-C.sub.1 -C.sub.4 alkyl, halogen;

R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, OH , -O-C(O)-(C.sub.1 -C.sub.4 alkyl), -O-(C.sub.1 -C.sub.4 alkyl), halogen, cyano, C.sub.1 -C.sub.6 alkyl, or trifluoromethyl, with the proviso that, when R.sub.1 is H, R.sub.2 is not OH;

X is selected from H, C.sub.1 -C.sub.6 alkyl, cyano, nitro, triflouromethyl, halogen;

Y is the moiety ##STR182## R.sub.7 and R.sub.8 are selected independently from H, C.sub.1 -C.sub.6 alkyl, or combined by -(CH.sub.2)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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONH(C.sub.1 -C.sub.4), -NH.sub.2, C.sub.1 -C.sub.4 alkylamino, di(C.sub.1 -C.sub.4)alkylamino, -NHSO.sub.2 (C.sub.1 -C.sub.4), -NHCO(C.sub.1 -C.sub.4), or -NO.sub.2 ;

or a pharmaceutically acceptable salt thereof.

3. A compound selected from the formulas I or II: ##STR183## wherein: R.sub.1 is selected from H, OH, -O-C(O)-C.sub.1 -C.sub.12 alkyl (straight chain or branched), -O-C.sub.1 -C.sub.12 alkyl (straight chain or branched or cyclic), or halogens; or C.sub.1 -C.sub.4 halogenated ethers.

R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, OH, -O-C(O)-C.sub.1 -C.sub.12 (straight chain or branched), -O-C.sub.1 -C.sub.12 (straight chain or branched or cyclic), halogens, or C.sub.1 -C.sub.4 halogenated ethers, cyano, C.sub.1 -C.sub.6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R.sub.1 is H, R.sub.2 is not OH;

X is selected from H, C.sub.1 -C.sub.6 alkyl, cyano, nitro, trifluoromethyl, halogen;

n is 2 or 3;

Y is the moiety: ##STR184## wherein: a) R.sub.7 and R.sub.8 are independently selected from the group of H, C.sub.1 -C.sub.6 alkyl, or phenyl optionally substituted by CN, C.sub.1 -C.sub.6 alkyl (straight chain or branched), C.sub.1 -C.sub.6 alkoxy (straight chain or branched), halogen, -OH, -CF.sub.3, or -OCF.sub.3 ; or

b) R.sub.7 and R.sub.8 are concatenated to form a pyrrolidine ring, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN-, -CONHR.sub.1,-NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, or -NO.sub.2 ; or

c) R.sub.7 and R.sub.8 are concatenated to form a piperidine ring, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1,-NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, or -NO.sub.2 ; or

d) R.sub.7 and R.sub.8 are concatenated to form an azepan ring, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, or -NO.sub.2 ; or

e) R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 acyloxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2, -NHSO.sub.2 R.sub.1, -NHCOR.sub.1, or -NO.sub.2 ;

or a pharmaceutically acceptable salt thereof.

4. A compound selected from the formulas I or II: ##STR185## wherein: R.sub.1 is selected from H, OH, -O-C(O)-(C.sub.1 -C.sub.4 alkyl), -O-(C.sub.1 -C.sub.4 alkyl), halogen, or C.sub.1 -C.sub.4 halogenated ethers;

R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, OH, -O-C(O)-(C.sub.1 -C.sub.4 alkyl), -O-(C.sub.1 -C.sub.4 alkyl), halogen, or C.sub.1 -C.sub.4 halogenated ethers, cyano, C.sub.1 -C.sub.6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R.sub.1 is H, R.sub.2 is not OH;

X is selected from H, C.sub.1 -C.sub.6 alkyl, cyano, nitro, trifluoromethyl, halogen;

n is 2or 3;

Y is the moiety: ##STR186## wherein R.sub.7 and R.sub.8 are independently selected from the group of H, C.sub.1 -C.sub.6 alkyl, or phenyl optionally substituted by CN, C.sub.1 -C.sub.6 alkyl (straight chain or branched), C.sub.1 -C.sub.6 alkoxy (straight chain or branched), halogen, -OH, -CF.sub.3, or -OCF.sub.3 ; or R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 alkylthio, -CN, -CO.sub.2 H, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2 or -NO.sub.2 ;

or a pharmaceutically acceptable salt thereof.

5. A compound of claim 4 wherein R.sub.1 is selected from H, OH, -O-C(O)-(C.sub.1 -C.sub.4 alkyl), -O-(C.sub.1 -C.sub.4 alkyl), halogen, or C.sub.1 -C.sub.4 halogenated ethers;

R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, OH, -O-C(O)-(C.sub.1 -C.sub.4 alkyl), -O-(C.sub.1 -C.sub.4 alkyl), halogen, or C.sub.1 -C.sub.4 halogenated ethers, cyano, C.sub.1 -C.sub.6 alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R.sub.1 is H, R.sub.2 is not OH;

X is selected from H, C.sub.1 -C.sub.6 alkyl, cyano, nitro, trifluoromethyl, halogen;

n is 2or 3;

Y is the moiety: ##STR188## wherein R.sub.7 and R.sub.8 are independently selected from the group of H or C.sub.1 -C.sub.6 alkyl; or R.sub.7 and R.sub.8 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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 alkylthio, -CN, -CO.sub.2 H, -CONHR.sub.1, -NH.sub.2, -NH(C.sub.1 -C.sub.4 alkyl), -N(C.sub.1 -C.sub.4 alkyl).sub.2 or -NO.sub.2 ;

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)-be nzyl]-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-indol e 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)-be nzyl]-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-yl ethoxy)-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]-be nzyl}-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-pi peridin-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-b icyclo[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)-benzy l]-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)-be nzyl]-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)-be nzyl]-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-m ethyl-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-y l-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-eth oxy)-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-m ethyl-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-trifluorom ethoxy-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]-pheno xy}-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)-eth oxy]-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-met hyl-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)-ben zyl]-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-methy l-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-ind ol-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-i ndol-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-ind ol-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-indo l-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-ind ol-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-indo l-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]-be nzyl}-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]-be nzyl}-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]-be nzyl}-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-p henyl)-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-in dol-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)-ben zyl]-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-in dol-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-pheny l)-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-ind ol-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]-1 H-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-in dol-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-indol e-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)-benz yl]-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]-1 H-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-in dole-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-phen yl)-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-i ndol-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-in dol-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)-benz yl]-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-ind ol-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-i ndole-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-indo le-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)-be nzyl]-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-y l-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)-ben zyl]-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-me thyl-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-in dol-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:

R.sub.1 is OH;

R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, OH or the C.sub.1 -C.sub.4 esters or alkyl ethers thereof, halogen, cyano, C.sub.1 -C.sub.6 alkyl, or trifluoromethyl, with the proviso that, when R.sub.1 is H, R.sub.2 is not OH;

X is selected from the group of Cl, NO.sub.2, CN, CF.sub.3, or CH.sub.3 ;

Y is the moiety ##STR190## R.sub.7 and R.sub.8 are concatenated together as -(CH.sub.2).sub.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, C.sub.1 -C.sub.4 alkyl, trihalomethyl, C.sub.1 -C.sub.4 alkoxy, trihalomethoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, hydroxy (C.sub.1 -C.sub.4)alkyl, -CO.sub.2 H, -CN, -CONH(C.sub.1 -C.sub.4), -NH.sub.2, C.sub.1 -C.sub.4 alkylamino, di(C.sub.1 -C.sub.4)alkylamino, -NHSO.sub.2 (C.sub.1 -C.sub.4), -NHCO(C.sub.1 -C.sub.4), and -NO.sub.2 ; or a pharmaceutically acceptable salt thereof.
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