Benzothiophene-based selective estrogen receptor downregulators

1. A compound of formula:

or a pharmaceutically acceptable salt thereof;

wherein:

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

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

X B is selected from —O—, —CH 2 —, —S—, —NH—, -NMe-, —CF 2 —, and —C 3 cycloalkyl-;

Y is —CF 2 — or —C 3 cycloalkyl-;

Ring B is phenyl, naphthyl, quinolinyl, 5- or 6-membered monocyclic heteroaryl or 7-, 8-, 9- or 10 membered bicyclic heterocyclyl;

Ring C is phenyl, thiophenyl, 5- or 6-membered monocyclic heteroaryl, or 7-, 8-, 9- or 10-membered bicyclic heterocyclyl;

R 1 is selected from hydroxyl, hydrogen, halogen, —O(C 1 -C 6 alkyl), —OC(O)(C 1 -C 6 alkyl), —OC(O)C 6 H 5 , —OC(O)O(C 1 -C 6 alkyl), —OC(O)OC 6 H 5 and —OSO 2 (C 2 -C 6 alkyl);

R 2 is selected from —CH═CHCOOH, —NH(CO)COOH, —COOH, —C 2 -C 6 alkenylene-COOH, and —C 2 -C 6 alkynylene-COOH;

R 3 is independently selected at each occurrence from hydrogen, halogen, —CN, —NO 2 , —C 1 -C 6 alkyl, and —C 1 -C 6 fluoroalkyl; and

R 4 is independently selected at each occurrence from hydrogen, halogen, hydroxyl, —C 1 -C 6 alkyl, —C 1 -C 6 fluoroalkyl, —CN, —O(C 1 -C 6 alkyl), and —O(C 1 -C 6 fluoroalkyl).

2. The compound of claim 1 , wherein X B is —O—.

3. The compound of claim 2 , wherein Y is —CF 2 —.

4. The compound of claim 2 , wherein Y is —C 3 cycloalkyl-.

5. The compound of claim 2 , wherein Ring B is phenyl.

6. The compound of claim 2 , wherein Ring C is phenyl.

7. The compound of claim 2 , wherein R 1 is hydroxyl.

8. The compound of claim 7 , wherein R 2 is —CH═CHCOOH.

9. The compound of claim 8 , wherein R 3 is hydrogen.

10. The compound of claim 9 , wherein R 4 is independently selected at each occurrence from halogen and —C 1 -C 6 alkyl.

11. The compound of claim 10 , wherein m is 0.

12. The compound of claim 11 , wherein n is 3.

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

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

19. A method of treating an estrogen receptor positive breast cancer in a human comprising administering to the human an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

20. The method of claim 19 , wherein the estrogen receptor positive breast cancer is metastatic.