Triphenylalkene derivatives and their use as selective estrogen receptor modulators

1. A compound of the formula:

wherein

R1 is H, halogen, OCH 3 , or OH;

R2 is

 where X is O, and n is an integer from 1 to 4; and

R4 and R5, which are the same or different, are a 1 to 4 carbon alkyl, H, —CH 2 C≡CH or —CH 2 CH 2 OH; or

R4 and R5 form an N-containing five- or six-membered ring or heteroaromatic ring; and

R3 is H, halogen, OH or —OCH 3 ;

or a stereoisomer; or a non-toxic pharmaceutically acceptable salt or ester thereof or mixtures thereof, provided that

a) when R2 is

 in the 4-position of the phenyl

where R4 and R5

i) are the same, either methyl or ethyl; or

ii) form an N-containing five-membered ring;

then R1 and R3 cannot simultaneously be H; and

b) when R2 is

 in the 4-position of the phenyl

where R4 and R5, which are the same or different, are methyl or H.

2. A compound according to claim 1 where n is 1, and

R4 and R5 are methyl or form a piperidine or imidazole ring.

3. A compound according to claim 1 , which is selected from the group consisting of

(2-{4-[4-chloro-1-(4-fluorophenyl)-2-phenylbut-1-enyl]phenoxy}ethyl)-dimethylamine,

(2-{4-[4-chloro-1-(4-chlorophenyl)-2-phenylbut-1-enyl]phenoxy}ethyl)-dimethylamine,

(2-{4-[4-chloro-1,2-bis(4-chlorophenyl)but-1-enyl]phenoxy}ethyl)-dimethylamine,

(2-{4-[4-chloro-2-(4-fluorophenyl)-1-phenylbut-1-enyl]phenoxy}ethyl)-dimethylaamine,

(2-{4-[4-chloro-2-(4-chlorophenyl)-1-phenylbut-1-enyl]phenoxy}ethyl)-dimethylamine,

(2-{4-[4-chloro-2-(4-chlorophenyl)-1-(4-methoxyphenyl)but-1-enyl]phenoxy}ethyl)dimethylamine,

{2-[3-(4-chloro-1,2-diphenylbut-1-enyl)phenoxy]ethyl}dimethylamine,

1-{2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethyl}-1H-imidazole,

(2-[4-(4-chloro-1,2-diphenylbut-1-enyl)phenoxy]ethyl}methylprop-2-ynylamine,

2-({2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethyl}methylamino)-ethanol,

3-{4-chloro-1-[4-(2-imidazol-1-yl-ethoxy)phenyl]-2-phenyl-but-1-enyl}-phenol,

1-(2-{4-[4-chloro-2-(2-chlorophenyl)-1-phenylbut-1-enyl]phenoxy}ethyl)-piperidine,

1-(2-{4-[4-chloro-2-(3-methoxyphenyl)-1-phenylbut-1-enyl]phenoxy}ethyl)-piperidine, and

1-(2-{4-[4-chloro-2-(2-methoxyphenyl)-1-phenylbut-1-enyl]phenoxy}ethyl)piperidine,

or a stereoisomer; or a non-toxic pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition comprising an amount effective to produce a tissue specific estrogenic and/or antiestrogenic effect of said selective estrogen receptor modulator compound according to claim 1 , or a stereoisomer, or a non-toxic pharmaceutically acceptable salt or ester thereof, and a pharmaceutically compatible acceptable carrier therefor.

5. A method of producing a tissue specific estrogenic and/or antiestrogenic effect in a subject in which such an effect is desired which comprises administering to said subject said selective estrogen receptor modulator compound according to claim 1 , a stereoisomer, or a non-toxic pharmaceutically acceptable salt or ester thereof in an amount sufficient to produce the desired effect.

6. A compound 2-(4-{4-chloro-1-[4-(2-hydroxyethoxy)phenyl]-2-phenyl-but-1-enyl}phenoxy)-1-ethanol, or a stereoisomer or a non-toxic pharmaceutically acceptable salt or ester thereof.

7. A pharmaceutical composition comprising an amount effective to produce a tissue specific estrogenic and/or antiestrogenic effect of said compound according to claim 6 , or a stereoisomer, or a non-toxic pharmaceutically acceptable salt or ester thereof, and a pharmaceutically compatible acceptable carrier therefor.

8. A method of producing a tissue specific estrogenic and/or antiestrogenic effect in a subject in which such an effect is desired which comprises administering to said subject said compound according to claim 6 , a stereoisomer, or a non-toxic pharmaceutically acceptable salt or ester thereof in an amount sufficient to produce the desired effect.