US2003130274A1PendingUtilityA1

2-Phenyl-1-[4-(2-aminoethoxy)benzyl-indoles as estrogenic agents

57
Assignee: WYETH CORPPriority: Apr 19, 1996Filed: Jul 10, 2002Published: Jul 10, 2003
Est. expiryApr 19, 2016(expired)· nominal 20-yr term from priority
Inventors:Chris P. MillerMichael D. ColliniBach D. TranArthur A. Santilli
A61P 5/32A61P 3/06A61P 5/00A61P 9/00A61P 5/30A61P 5/24A61P 35/00A61P 25/28C07D 405/04A61P 19/10A61K 31/454A61K 31/404C07D 209/10A61K 31/405A61P 13/08A61K 31/496A61P 19/00C07D 209/30A61P 15/00C07D 405/12C07D 209/08C07D 403/12A61P 19/02A61P 17/10A61K 31/55C07D 209/42A61K 31/4523C07D 209/12
57
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Claims

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:

Claims

exact text as granted — not AI-modified
What is claimed:  
     
         1 . A compound selected from the formulas I or II:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is selected from H, OH or the C 1 -C 12  esters (straight chain or branched) or C 1 -C 12  (straight chain or branched or cyclic) alkyl ethers thereof, or halogens; or C 1 -C 4  halogenated ethers including triflouromethyl ether and trichloromethyl ether.  
 R 2 , R 3 , R 4 , R 5 , and R6 are independently selected from H, OH or the C 1 -C 12  esters (straight chain or branched) or C 1 -C 12  alkyl ethers (straight chain or branched or cyclic) thereof, halogens, or C 1 -C 4  halogenated ethers including triflouromethyl ether and trichloromethyl ether, cyano, C 1 -C 6  alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R 1  is H, R 2  is not OH.  
 X is selected from H, C 1 -C 6  alkyl, cyano, nitro, trifluoromethyl, halogen;  
 n is 2 or 3;  
 Y is selected from: 
 a) the moiety:  
                     wherein R 7  and R 8  are independently selected from the group of H, C 1 -C 6  alkyl, or phenyl optionally substituted by CN, C 1 -C 6  alkyl (straight chain or branched), C 1 -C 6  alkoxy (straight chain or branched), halogen, —OH, —CF 3 , or —OCF 3 ;    
 b) a five-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4  alkyl)-, —N═, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4  alkyl, trihalomethyl, C 1 -C 4  alkoxy, trihalomethoxy, C 1 -C 4  acyloxy, C 1 -C 4  alkylthio, C 1 -C 4  alkylsulfinyl, C 1 -C 4  alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4  alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with 1-3 (C 1 -C 4 )alkyl;  
 c) a six-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4  alkyl)-, —N═, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4  alkyl, trihalomethyl, C 1 -C 4  alkoxy, trihalomethoxy, C 1 -C 4  acyloxy, C 1 -C 4  alkylthio, C 1 -C 4  alkylsulfinyl, C 1 -C 4  alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4  alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with 1-3 (C 1 -C 4 )alkyl;  
 d) a seven-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4  alkyl)-, —N═, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4  alkyl, trihalomethyl, C 1 -C 4  alkoxy, trihalomethoxy, C 1 -C 4  acyloxy, C 1 -C 4  alkylthio, C 1 -C 4  alkylsulfinyl, C 1 -C 4  alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4  alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with 1-3 (C 1 -C 4 )alkyl; or  
 e) a bicyclic heterocycle containing from 6-12 carbon atoms either bridged or fused and contaning up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C 1 C 4  alkyl)-, and —S(O) m —, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C 1 -C 4  alkyl, trihalomethyl, C 1 -C 4  alkoxy, trihalomethoxy, C 1 -C 4  acyloxy, C 1 -C 4  alkylthio, C 1 -C 4  alkylsulfinyl, C 1 -C 4  alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H—, —CN—, —CONHR 1 —, —NH 2 —, C 1 -C 4  alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 R 1 —, —NHCOR 1 —, —NO 2 , and phenyl optionally substituted with 1-3 (C 1 -C 4 ) alkyl;  
 and the pharmaceutically acceptable salts thereof.  
 
 
     
     
         2 . A compound of  claim 1  wherein: 
 R 1  is selected from H, OH or the C 1 -C 4  esters or alkyl ethers thereof, halogen;  
 R 2 , R 3 , R 4 , R 5 , and R 6  are independently selected from H, OH or the C 1 -C 4  esters or alkyl ethers thereof, halogen, cyano, C 1 -C 6  alkyl, or trifluoromethyl, with the proviso that, when R 1  is H, R 2  is not OH;  
 X is selected from H, C 1 -C 6  alkyl, cyano, nitro, triflouromethyl, halogen;  
 Y is the moiety  
                     
 R 7  and R 8  are selected independently from H, C 1 -C 6  alkyl, or combined by —(CH 2 )p—, wherein p is an integer of from 2 to 6, so as to form a ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C 1 -C 4  alkyl, trihalomethyl, C 1 -C 4  alkoxy, trihalomethoxy, C 1 -C 4  alkylthio, C 1 -C 4  alkylsulfinyl, C 1 -C 4  alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 ), —NH 2 , C 1 -C 4  alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 (C 1 -C 4 ), —NHCO(C 1 -C 4 ), and —NO 2 ;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         3 . A compound of  claim 1  wherein: 
 R 1  is OH;  
 R 2 , R 3 , R 4 , R 5 , and R 6  are independently selected from H, OH or the C 1 -C 4  esters or alkyl ethers thereof, halogen, cyano, C 1 -C 6  alkyl, or trifluoromethyl, with the proviso that, when R 1  is H, R 2  is not OH;  
 X is selected from the group of Cl, NO 2 , CN, CF 3 , or CH 3 ;  
 Y is the moiety  
                     
 R 7  and R 8  are concatenated together as —(CH 2 ) r —, wherein r is an integer of from 4 to 6, to form a ring optionally substituted by up to three subsituents selected from the group of hydrogen, hydroxyl, halo, C 1 -C 4  alkyl, trihalomethyl, C 1 -C 4  alkoxy, trihalomethoxy, C 1 -C 4  alkylthio, C 1 -C 4  alkylsulfinyl, C 1 -C 4  alkylsulfonyl, hydroxy (C 1 -C 4 )alkyl, —CO 2 H, —CN, —CONH(C 1 -C 4 ), —NH 2 , C 1 -C 4  alkylamino, di(C 1 -C 4 )alkylamino, —NHSO 2 (C 1 -C 4 ), —NHCO(C 1 -C 4 ), and —NO 2 ;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         4 . 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.  
     
     
         5 . 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.  
     
     
         6 . 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.  
     
     
         7 . 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.  
     
     
         8 . 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.  
     
     
         9 . 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.  
     
     
         10 . 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.  
     
     
         11 . 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.  
     
     
         12 . 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.  
     
     
         13 . 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.  
     
     
         14 . 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.  
     
     
         15 . 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.  
     
     
         16 . 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.  
     
     
         17 . 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.  
     
     
         18 . 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.  
     
     
         19 . 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.  
     
     
         20 . A compound of  claim 1  which is 5-Benzyloxy-2-[4-isopropoxy-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-[4-methyl-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 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-benzyloxy-2-(3-benzyloxy-phenyl)-3-methyl-1H-indole or a pharmaceutically acceptable salt thereof.  
     
     
         23 . 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.  
     
     
         24 . A compound of  claim 1  which is 5-Benzyloxy-2-(4-benzyloxy-3-fluoro-phenyl)-3-methyl-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof.  
     
     
         25 . 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.  
     
     
         26 . 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 phanmaceutically acceptable salt thereof.  
     
     
         27 . A compound of  claim 1  which is (2-{4-[5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-indol-1-yl-methyl]-phenoxy}-ethyl)-cyclohexyl-amine or a pharmaceutically acceptable salt thereof.  
     
     
         28 . 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.  
     
     
         29 . 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.  
     
     
         30 . A compound of  claim 1  which is 4-{3-Methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole} (HCl).  
     
     
         31 . 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).  
     
     
         32 . A compound of  claim 1  which is 3-Methyl-2-phenyl-1-[4-(2-piperidine-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl).  
     
     
         33 . 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.  
     
     
         34 . 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.  
     
     
         35 . 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 (HCL).  
     
     
         36 . 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 (HCL).  
     
     
         37 . 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.  
     
     
         38 . 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.  
     
     
         39 . 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).  
     
     
         40 . A compound of  claim 1  which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-3-methyl-2-phenyl-1H-indol-5-ol (HCl).  
     
     
         41 . 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.  
     
     
         42 . 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).  
     
     
         43 . 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.  
     
     
         44 . A compound of  claim 1  which is 1-[4-(2-Azocan-1-yl-ethoxy)-benzyl]-2-(4hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.  
     
     
         45 . 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.  
     
     
         46 . 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.  
     
     
         47 . 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.  
     
     
         48 . 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.  
     
     
         49 . 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.  
     
     
         50 . 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.  
     
     
         51 . A compound of  claim 1  which is 2-(4Hydroxy-phenyl)-3-methyl-1-{4-[2-(2-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.  
     
     
         52 . A compound of  claim 1  which is 2-(4-Hydroxy-phenyl)-3-methyl-1-{4-[2-(3-methyl-piperdin-1-yl)-ethoxy]-benzyl}-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-(4-methyl-piperidin-1-yl)-ethoxy]-benzyl}-1H-indol-5-ol (HCl).  
     
     
         54 . 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.  
     
     
         55 . 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.  
     
     
         56 . 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.  
     
     
         57 . 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.  
     
     
         58 . A compound of  claim 1  which is 2-(4-Hydroxy-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.  
     
     
         59 . 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).  
     
     
         60 . A compound of  claim 1  which is 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4fluoro-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.  
     
     
         61 . A compound of  claim 1  which is 2-(3-Methoxy-4hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl).  
     
     
         62 . 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 (HCL).  
     
     
         63 . 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).  
     
     
         64 . 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).  
     
     
         65 . A compound of  claim 1  which is 2-(4Cyclopenyloxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.  
     
     
         66 . 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.  
     
     
         67 . 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.  
     
     
         68 . A compound of  claim 1  which is 2-(4Chloro-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCL).  
     
     
         69 . 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.  
     
     
         70 . 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.  
     
     
         71 . 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.  
     
     
         72 . 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.  
     
     
         73 . 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.  
     
     
         74 . 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.  
     
     
         75 . 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.  
     
     
         76 . 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).  
     
     
         77 . A compound of  claim 1  which is Removal of benzyl ethers to render 3-Chloro-2-(4-hydroxy-phenyl)-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol (HCl).  
     
     
         78 . 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).  
     
     
         79 . A compound of  claim 1  which is 3-Chloro-2-(4-hydroxy-2-methyl-phenyl)-1-[4-(2-pipenrdin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol or a pharmaceutically acceptable salt thereof.  
     
     
         80 . 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).  
     
     
         81 . 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).  
     
     
         82 . 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).  
     
     
         83 . 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.  
     
     
         84 . 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.  
     
     
         85 . 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.  
     
     
         86 . 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.  
     
     
         87 . A compound of  claim 1  which is 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-cyan-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-cyano-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole or a pharmaceutically acceptable salt thereof.  
     
     
         89 . 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 (HCl).  
     
     
         90 . 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 (HCl).  
     
     
         91 . 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.  
     
     
         92 . 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.  
     
     
         93 . 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.  
     
     
         94 . 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.  
     
     
         95 . 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.  
     
     
         96 . 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.  
     
     
         97 . 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 or a pharmaceutically acceptable salt thereof.  
     
     
         98 . 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.  
     
     
         99 . 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.  
     
     
         100 . 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.  
     
     
         101 . 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.  
     
     
         102 . 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.  
     
     
         103 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.  
     
     
         104 . 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.  
     
     
         105 . A method of treating or preventing disease states or syndromes which are caused or associated with an estrogen deficiency 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.  
     
     
         106 . A method of treating or preventing cardiovascular disease 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 method of treating or preventing disease in a mammal which result from proliferation or abnormal development, actions or growth of endometrial or endometrial-like tissue, 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.

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