Benzothiophene estrogen receptor modulators

Patent metadata

Field	Value
Publication number	US-10981887-B2
Application number	US-202016824290-A
Country	US
Kind code	B2
Filing date	Mar 19, 2020
Priority date	Feb 10, 2017
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder.

First claim

I claim:

1. A compound selected from:

or a pharmaceutically acceptable salt thereof;
wherein
X is

m is 0, 1, or 2;
o is 0, 1, 2, 3, 4, or 5;
Z is selected from —O—, —C(R 3 ) 2 —, —CHR 3 —, —CH 2 —, —CHF—, —CF 2 —, and —S—;
each R 1 is independently selected from C 1 -C 3 alkyl, halogen, and C 1 -C 3 haloalkyl;
R 2 is selected from:
a) 4-6 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;
b) —NH 2 , —NH(C 1 -C 3 alkyl or C 2 -C 3 haloalkyl), and —N((independently)C 1 -C 3 alkyl or C 2 -C 3 haloalkyl) 2 ;
c) monocyclic 7-8 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ; and
d) 6-12 membered bicyclic or bridged heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;

R 3 is independently selected from —F, —Cl, —Br, —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 ; and
R 4 and R 5 are independently selected from halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl.

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

3. The compound of claim 1 , wherein o is 3.

4. The compound of claim 1 , wherein o is 0, 1, or 2.

5. The compound of claim 1 , wherein at least one R 1 is —F.

6. The compound of claim 1 , wherein at least one R 1 is methyl.

7. The compound of claim 1 , wherein R 2 is —N(CH 2 CH 3 ) 2 .

8. The compound of claim 1 , wherein R 2 is selected from

9. The compound of claim 1 , wherein R 3 is —F.

10. The compound of claim 1 , wherein R 4 is —F.

11. The compound of claim 1 , wherein R 4 is C 1 -C 3 haloalkyl.

12. The compound of claim 1 , wherein R 5 is halogen.

13. The compound of claim 1 , wherein R 5 is C 1 -C 3 haloalkyl.

14. The compound of claim 1 selected from

or a pharmaceutically acceptable salt thereof.

15. 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.

16. A method of treating a hormone-related cancer that is estrogen mediated comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

17. The method of claim 16 , wherein the subject is a human.

18. The method of claim 16 , wherein the cancer is breast, endometrial or ovarian cancer.

19. The method of claim 17 , wherein an effective amount of an additional therapeutic agent is administered.

Assignees

• G1 Therapeutics Inc

Inventors

• Strum Jay Copeland

Classifications

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D333/64 Primary

  Oxygen atoms · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title