Cycloalkylidene compounds as modulators of estrogen receptor
The present invention relates to novel compounds with a variety of therapeutic uses, more particularly novel substituted cyclic alkylidene compounds that are particularly useful for selective estrogen receptor modulation.
1. A method for treating a condition selected from osteoporosis, obesity, breast cancer, depression, vaginal dryness, rheumatoid arthritis, vasomotor symptoms, and urogenital or vulvar vaginal atrophy in an mammal in need thereof, said method comprising administering to the mammal a therapeutically effective amount of a compound of formula (I):
or a pharmaceutically acceptable salt thereof wherein
each R 2 is independently selected from OH, alkyl, or halogen;
q is independently selected from 0, 1, or 2;
X is —(CH 2 ) n — where n is 0, 1, 2, or 3, —C(R g ) 2 —, or —O—;
each of R 6 and R 7 are selected from H or alkyl;
R 8 is —CO 2 H, —(R h ) t CO 2 H, or —CONR a R b ;
t is 1 to 8;
R a is H, alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl;
R b is H, alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl;
or
R a and R b may combine with the atoms to which they are bound to form a heteroaryl or heterocyclyl ring;
R g is alkyl; and
each R h independently is —CR j R k —, where each of R j and R k independently are selected from H and alkyl.
2. The method of claim 1 , wherein the condition is vasomotor symptoms.
3. The method of claim 1 , wherein the condition is vulvar vaginal atrophy.
4. The method of claim 1 , wherein alkyl is C 1-8 alkyl.
5. The method of claim 1 , wherein q is 0.
6. The method of claim 1 , wherein each of R 6 and R 7 are H or C 1-8 alkyl.
7. The method of claim 1 , wherein X is —(CH 2 ) n —.
8. The method of claim 1 , wherein n is 1.
9. The method of claim 1 , wherein R 6 and R 7 are hydrogen.
10. A method for treating a condition selected from osteoporosis, obesity, breast cancer, depression, vaginal dryness, rheumatoid arthritis, vasomotor symptoms, and urogenital or vulvar vaginal atrophy in an human in need thereof, said method comprising administering to the human a therapeutically effective amount of a compound of formula
or a pharmaceutically acceptable salt thereof.
11. The method of claim 10 , wherein the condition is vasomotor symptoms.
12. The method of claim 10 , wherein the condition is vulvar vaginal atrophy.
13. The method of claim 11 , wherein the compound is a pharmaceutically acceptable salt.
14. The method of claim 11 , wherein the compound is 4-[(4-Hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]benzoic acid.