Naphthalene compounds as selective estrogen receptor modulators

1. A compound of formula (I):

including salts thereof wherein:

R 1 is H, OH, alkoxy, or halogen;

R 2 is H, OH, or halogen;

R 3 is alkyl, haloalkyl, cycloalkyl, alkoxy, or alkoxyalkyl;

R 4 is H or alkoxy;

R 5 is halogen or haloalkyl;

R 6 is —(Y)z-R7;

z is 0 or 1;

Y is —C≡C— or —CR e ═CR f —;

when z is 0, then R 7 is —CO-piperidinyl, —CO 2 H, —NHSO 2 -phenyl, NHCOCH 2 CO 2 NHSO 2 alkyl optionally substituted with halogen, alkyl substituted with CO 2 H, —CO 2 -alkyl, —O-alkyl-CO 2 H, or —O-alkyl-O-alkyl-OH;

when z is 1,then R 7 is —CO 2 H, —CO-piperazinyl, —CO-pyrrolidinyl, —CONH 2 or —PO 2 H 2 ;

R 8 is phenyl, optionally substituted with OH, halogen, or haloalkyl; and

R e and R f each independently are selected from H, alkyl, halogen, and haloalkyl.

2. A compound of formula (I):

including salts thereof wherein:

R 1 is H, OH, alkoxy, or halogen;

R 2 is H, OH, or halogen;

R 3 is alkyl, haloalkyl, cycloalkyl, alkoxy, or alkoxyalkyl;

R 4 is H or alkoxy;

R 5 is halogen or haloalkyl;

R 6 is —(Y)z-R7;

z is 0 or 1;

Y is —C≡O— or —CR e ═CR f ;

when z is 0, then R 7 is —CO-piperidinyl, —CO 2 H, —NHSO 2 -phenyl, NHCOCH 2 CO 2 H, —NHSO 2 alkyl optionally substituted with halogen, alkyl substituted with —CO 2 H, CO 2 -alkyl, —O-alkyl-CO 2 H, or —O-alkyl-O-alkyl-OH

when z is 1, then R 7 is —CO 2 H, —CO-piperazinyl, —CO-pyrrolidinyl, —CONH 2 or —PO 2 H 2 ;

R 8 is phenyl, optionally substituted with OH, halogen, or haloalkyl; and

Re and Rf each independently are selected from H, alkyl, halogen, and haloalkyl.

3. The compound of claim 2 wherein alkyl is C 1-9 alkyl.

4. The compound of claim 2 wherein R 1 is H or OH.

5. The compound of claim 4 wherein R 1 is OH.

6. The compound of claim 2 wherein R 2 is H, OH, or F.

7. The compound of claim 2 wherein R 3 is alkyl or haloalkyl.

8. The compound of claim 2 wherein R 4 is H.

9. The compound of claim 2 wherein R 5 is haloalkyl.

10. The compound of claim 2 wherein z is 1, Y is —CR e ═CR f , R e and R f each are H, and R 7 is —CO 2 H.

11. The compound of claim 2 wherein z is 0 and R 7 is —CO 2 H.

12. The compound of claim 2 wherein R 8 is phenyl, or phenyl monosubstituted with halogen.

13. The compound of claim 12 wherein R 8 is phenyl, 3-fluorophenyl, or 4-fluorophenyl.

14. A compound selected from

(2E)-3-[4-[(6-hydroxy-3-methyl-2-phenyl-1-naphthalenyl)oxy]-2-(trifluoromethyl)phenyl]-2-propenoic acid;

(2E)-3-[4-[(6-hydroxy-3-methyl-2-phenyl-1-naphthalenyl)oxy]-3-(trifluoromethyl)phenyl]-2-propenoic acid;

3-{4-[2-(4-Fluoro-phenyl)-6-hydroxy-3-propyl-naphthalen-1-yloxy]-2-trifluoromethyl-phenyl}-2-methyl-acrylic acid;

3-{4-[2-(4-Fluoro-phenyl)-6-hydroxy-3-propyl-naphthalen-1-yloxy]-2-trifluoromethyl-phenyl}-2-methyl-acrylamide;

(2E)-3-[4-[(3-methyl-2-phenyl-1-naphthalenyl)oxy]-2-(trifluoromethyl)phenyl]-2-propenoic acid;

N-[4-[(6-hydroxy-3-methyl-2-phenyl-1-naphthalenyl)oxy]-2-(trifluoromethyl)phenyl]methanesulfonamide;

4-{[2-(4-fluorophenyl)-6-hydroxy-3-methyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)benzoic acid;

(2E)-3-[4-{[2-(3-fluorophenyl)-6-hydroxy-3-methyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)phenyl]-2-propenoic acid;

(2E)-3-[4-{[2-(4-fluorophenyl)-6-hydroxy-3-propyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)phenyl-2-propenoic acid;

(2E)-3-[4-{[2-(4-fluorophenyl)-6-hydroxy-3-propyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)phenyl-2-propenamide;

4-{[2-(4-fluorophenyl)-6-hydroxy-3-methyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)benzamide;

Methyl 4-{[2-(3-fluorophenyl)-6-hydroxy-3-methyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)benzoate;

6-(3-fluorophenyl)-5-{[4-({2-[(2-hydroxyethyl)oxy]ethyl}oxy)-3-(trifluoromethyl)phenyl]oxy}-7-methyl-2-naphthalenol;

{[4-{[2-(3-fluorophenyl)-6-hydroxy-3-methyl-1-naphthalenyl]oxy}-2-(trifluoromethyl)phenyl]oxy}acetic acid; and

6-(3-fluorophenul)-5-{[4-[(2-hydroxyethyl)oxy-3-(trifluoromethyl)phenyl]oxy}-7-methyl-2-naphthslenol,

including pharmaceutically acceptable salts thereof.

15. (2E)-3-[4-{[2-(3-fluorophenyl)-6-hydroxy-3-methyl-1-naphthaleneyl]oxy}-2-(trifluoromethyl)phenyl]-2-propenoic acid, including pharmaceutically acceptable salts thereof.

16. A pharmaceutical composition comprising a compound according to claim 2 , and a pharmaceutically acceptable carrier.

17. A compound according to claim 2 for use as an active therapeutic substance.