Selective estrogen receptor degraders

Patent metadata

Field	Value
Publication number	US-10654866-B2
Application number	US-201916508745-A
Country	US
Kind code	B2
Filing date	Jul 11, 2019
Priority date	Jul 12, 2018
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

Novel selective estrogen receptor degraders (SERDs) according to the formula:

pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein either R 1 or R 2 is independently selected from Cl, F, —CF 3 , or —CH 3 , and the other is hydrogen, and methods for their use are provided.

First claim

We claim:

1. A compound of the formula:

wherein either R 1 or R 2 is independently selected from Cl, F, —CF 3 , or —CH 3 , and the other is hydrogen,
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein the pharmaceutically acceptable salt is a benzenesulfonic acid salt.

5. The compound according to claim 1 , wherein the pharmaceutically acceptable salt is a 4-methylbenzenesulfonic acid salt.

6. The compound according to claim 2 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 6 , wherein the pharmaceutically acceptable salt is a benzenesulfonic acid salt.

8. The compound according to claim 6 , wherein the pharmaceutically acceptable salt is a 4-methylbenzenesulfonic acid salt.

9. The compound according to claim 6 , wherein the compound is

10. The compound according to claim 3 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 , wherein the pharmaceutically acceptable salt is a benzenesulfonic acid salt.

12. The compound according to claim 10 , wherein the pharmaceutically acceptable salt is a 4-methylbenzenesulfonic acid salt.

13. The compound according to claim 10 , wherein the compound is

14. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 in combination with a pharmaceutically acceptable excipient, carrier, or diluent.

15. The pharmaceutical composition according to claim 14 , comprising one or more other therapeutic agents.

16. A method of treating breast cancer, ovarian cancer, endometrial cancer, prostate cancer, uterine cancer, gastric cancer, or lung cancer, comprising administering to a patient in need of such treatment an effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 1 .

17. The method according to claim 16 , wherein the breast cancer is ER-positive breast cancer.

18. The method according to claim 16 , wherein the gastric cancer is ER-positive gastric cancer.

19. The method according to claim 16 , wherein the lung cancer is ER-positive lung cancer.

Assignees

• Lilly Co Eli

Inventors

• Bastian Jolie Anne
• Cohen Jeffrey Daniel
• Rubio Almudena
• Sall Daniel Jon

Classifications

• C07D491/052 Primary

  the oxygen-containing ring being six-membered · CPC title

• A61K45/06

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

• A61P35/00

  Antineoplastic agents · CPC title

• C07D401/12

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

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title