Benzothiophene-based selective estrogen receptor downregulator compounds
This invention is benzothiophene-based estrogen receptor downregulators and their compositions and uses to treat estrogen-related medical disorders.
1. A compound, or a pharmaceutically acceptable salt thereof of Formula
wherein:
m is 0, 1, 2, 3, or 4;
n is 0, 1, 2, 3, or 4;
Ring D is phenyl, naphthyl, quinolinyl, 5- or 6-membered monocyclic heteroaryl, cycloalkyl, or 7-, 8-, 9- or 10-membered bicyclic heterocyclyl;
Ring E is phenyl, heteroaryl, 5- or 6-membered monocyclic heteroaryl, cycloalkyl or 7-, 8-, 9- or 10-membered bicyclic heterocyclyl;
R 12 and R 13 are independently selected at each occurrence from —OR 15 , —SR 15 , —N(R 15 ) 2 , hydrogen, aryl, heteroaryl, halogen, —CN, —NO 2 , haloalkyl, cycloalkyl, thiol, nitroso, C 1 -C 6 alkyl, hydroxyl, —O(C 1 -C 6 alkyl), —O(C 1 -C 6 fluoroalkyl), —SF 5 , —B(OH) 2 , —B(OR 15 ) 2 , —C(O)OR 15 , —C(O)R 16 , —C(S)OR 15 , —C(S)R 16 , —OSO 2 OR 15 , —OSO 2 R 16 , —NHSO 2 OR 15 , —NHSO 2 R 16 , —N(alkyl)SO 2 OR 15 , —N(alkyl)SO 2 R 16 , —OP(O)(OR 15 ) 2 , —OP(O)(R 16 ) 2 , —P(O)(OR 15 ) 3 , —P(O)(R 16 ) 3 , —P(O)OR 15 , —P(O)R 16 , —SO 2 R 16 , —SO 2 OR 15 , alkyne, alkene, arylalkyl, aryloxy, heteroarylalkyl, and C 1 -C 6 fluoroalkyl;
R 15 is independently selected at each occurrence from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; and
R 16 is selected from the group consisting of —N(R 15 ) 2 , —SR 15 , and —OR 15 ; and
R 17 is hydrogen.
2. The compound of claim 1 , wherein R 16 is —OCH 3 .
3. The compound of claim 1 , wherein Ring D is phenyl, naphthyl or quinolinyl.
4. The compound of claim 3 , wherein Ring E is phenyl or thienyl.
5. The compound of claim 1 , wherein R 12 is independently selected at each occurrence from hydrogen, halogen, and C 1 -C 6 alkyl, wherein C 1 -C 6 alkyl is methyl.
6. The compound of claim 1 , wherein R 13 is independently selected at each occurrence from hydrogen, halogen, and C 1 -C 6 alkyl, wherein C 1 -C 6 alkyl is methyl.
7. The compound of claim 1 , wherein m is 0.
8. The compound of claim 1 , wherein n is 1 or 2.
9. The compound of claim 1 , wherein n is 3.
10. The compound of claim 1 selected from
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 selected from
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 selected from
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 of Formula
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
15. A method of treating an estrogen-related disorder in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.