Substituted (4'-hydroxyphenyl)cyclohexane compounds and uses thereof as selective agonists of the estrogen receptor beta isoform
Disclosed are substituted (4′-hydroxylphenyl)cycloalkane compounds and there use as selective agonists of the estrogen receptor beta isoform (ERβ). The disclosed compounds may be formulated as pharmaceutical compositions and administered to treat diseases associated with ER activity, such as proliferative diseases and disorders and/or psychiatric diseases or disorders.
1. A compound of a Formula Ia below or a pharmaceutically acceptable salt thereof:
wherein:
X is hydroxyl, hydroxymethyl, or aminoethyl;
Y is hydrogen or alkyl, provided that when X is hydroxyl then Y is not hydrogen; or
X and Y together form hydroxyalkylidenyl, aminoalkylidenyl, or oxime; and
Z is CH.
2. The compound of claim 1 , wherein X is hydroxymethyl.
3. The compound of claim 2 , wherein Y is hydrogen or alkyl.
4. The compound of claim 1 , wherein the compound has a formula:
5. The compound of claim 1 , wherein X is hydroxyl and Y is alkyl.
6. The compound of claim 1 , wherein the compound has a formula selected from:
7. A pharmaceutical composition comprising a suitable carrier and the compound of claim 1 .
8. A pharmaceutical composition comprising a suitable carrier and the compound of claim 4 .
9. A method for treating a patient a disease or disorder associated with estrogen receptor β (ERβ) activity, the method comprising administering to the patient the pharmaceutical composition of claim 7 .
10. The method of claim 9 , wherein the disease or disorder is a psychiatric disease or disorder.
11. The method of claim 9 , wherein the disease or disorder is a cell proliferative disease or disorder.
12. A method for treating a patient a disease or disorder associated with estrogen receptor β (ERβ) activity, the method comprising administering to the patient the pharmaceutical composition of claim 8 .
13. The method of claim 12 , wherein the disease or disorder is a psychiatric disease or disorder.
14. The method of claim 12 , wherein the disease or disorder is a cell proliferative disease or disorder.
15. The compound of claim 1 , wherein the compound has a formula:
16. A pharmaceutical composition comprising a suitable carrier and the compound of claim 15 .
17. A method for treating a patient a disease or disorder associated with estrogen receptor β (ERβ) activity, the method comprising administering to the patient the pharmaceutical composition of claim 16 .
18. The method of claim 17 , wherein the disease or disorder is a psychiatric disease or disorder.
19. The method of claim 17 , wherein the disease or disorder is a cell proliferative disease or disorder.