BENZOTHIOPHENE ESTROGEN RECEPTOR MODULATORS TO TREAT MEDICAL DISORDERS

1 . A compound selected from:

or a pharmaceutically acceptable salt thereof;

wherein

A is:

m is 1, 2, or 3;

n is 0, 1, 2, 3, or 4;

o is 0, 1, 2, 3, 4, or 5;

each Q is independently selected from the group consisting of —CHR 5 — and —CH 2 —;

Z 1 is —O—, —C(R 3 ) 2 —, or —S—;

Z 2 is bond, —O—, —C(R 3 ) 2 —, or —S—;

Z 3 is —O— or —S—;

each R 1 is independently selected from the group consisting of C 1 -C 5 alkyl, halogen, and C 1 -C 3 haloalkyl;

R 2 is selected from the group consisting of hydroxyl, alkoxy, —NH—(CH 2 ) n1 —NR 6 R 7 , —NR 6 R 7 , 4-10 membered heterocycle, and 6-12 membered bicyclic heterocycle; wherein each heterocycle is optionally substituted with one, two, or three groups independently selected from R 4 ;

n1 is 2, 3, 4, 5, or 6;

each R 3 is independently selected from the group consisting of hydrogen, halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl;

each R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl, —COOH, —COOC 1 -C 5 alkyl, —CONH 2 , —CON(H)alkyl, and —CON(alkyl) 2 ;

or two R 4 substituents on the same carbon atom are optionally combined together with the carbon to which they are attached to form a

group, wherein n3 is 1, 2, 3, 4, or 5;

R 6 and R 7 are independently selected at each instance from the group consisting of hydrogen, C 1 -C 12 alkyl, and C 2 -C 12 haloalkyl;

R 8 is selected from the group consisting of —C(O)R 9 , —OC(O)R 9 , —OP(O)(OR 10 ) 2 , and —P(O)(OR 10 ) 2 ;

R 9 is selected from the group consisting of hydrogen, C 1 -C 5 alkyl, —OR 6 , and —NR 6 R 7 ;

each R 10 is independently selected from the group consisting of hydrogen, C 1 -C 5 alkyl, and —C(O)C 1 -C 5 alkyl;

R 11 is a 4-10 membered monocyclic heterocycle or a 6-12 membered bicyclic heterocycle;

wherein each heterocycle is optionally substituted with one, two, or three substituents independently selected from R 4 , and wherein the heterocycle is attached through a carbon atom;

R 12 is a 5, 6, or 7-membered monocyclic or 6-12 membered bicyclic heterocycle; wherein each heterocycle is optionally substituted with one, two, or three substituents independently selected from R 4 , and wherein the heterocycle is attached through a carbon atom;

R 13 is selected from the group consisting of hydroxyl, —C(O)R 9 , —OC(O)R 9 , —OP(O)(OR 10 ) 2 , and —P(O)(OR 10 ) 2 ;

and R 14 , R 15 , and R 16 are independently selected from the group consisting of hydrogen, C 1 -C 5 alkyl, halogen, and C 1 -C 3 haloalkyl; wherein at least one of R 14 , R 15 , and R 16 is C 1 -C 5 alkyl, halogen, or C 1 -C 3 haloalkyl.

2 . The compound of claim 1 , wherein the compound is of Formula:

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 2 , wherein A is

4 . The compound of claim 2 , wherein R 8 is —C(O)R 9 .

5 . The compound of claim 2 , wherein R 8 is —OC(O)R 9 or —OP(O)(OR 10 ) 2 .

6 . The compound of claim 1 , wherein the compound is of Formula:

or a pharmaceutically acceptable salt thereof.

7 . The compound of claim 6 , wherein Y is

8 . The compound of claim 1 , wherein the compound is of Formula:

or a pharmaceutically acceptable salt thereof.

9 . The compound of claim 8 , wherein Z is

10 . The compound of claim 8 , wherein Z is

11 . The compound of claim 1 , wherein R 13 is hydroxyl.

12 . The compound of claim 1 , wherein at least one of Z 1 , Z 2 , and Z 3 is —O—.

13 . The compound of claim 1 , wherein Z 1 , Z 2 , and Z 3 are —O—.

14 . The compound of claim 1 , wherein n is 0.

15 . The compound of claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

16 . The compound of claim 15 , wherein the compound is of structure:

or a pharmaceutically acceptable salt thereof.

17 . The compound of claim 15 , wherein the compound is of structure:

or a pharmaceutically acceptable salt thereof.

18 . The compound of claim 15 , wherein the compound is of structure:

or a pharmaceutically acceptable salt thereof.

19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

20 . A method of treating an estrogen-related disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.