TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE

• US 20180141913A1
• Filed: 11/22/2017
• Published: 05/24/2018
• Est. Priority Date: 11/24/2016
• Status: Abandoned Application

• Current Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Original Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Inventors: BOCK, Mark, HAO, Ming-Hong, KORPAL, Manav, NYAVANANDI, Vijay Kumar, PUYANG, Xiaoling, SAMAJDAR, Susanta, SMITH, Peter Gerard, WANG, John, ZHENG, Guo Zhu, ZHU, Ping, MITCHELL, Lorna Helen, LARSEN, Nicholas, RIOUX, Nathalie, PRAJAPATI, Sudeep, REYNOLDS, Dominic, O'SHEA, Morgan, SAMARAKOON, Thiwanka
• Application Number:
  US15/821,367
• Publication Number:
  US 20180141913A1
• Time in Patent Office: Days
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 231/56 Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.

Claims

1. A compound given by the following formula:

8. The compound or pharmaceutically acceptable salt of claim 1, wherein R₁ is —

F.

10. The compound or pharmaceutically acceptable salt of claim 1, wherein R₂ is —

CH₂—

CF₃.

13. The compound or pharmaceutically acceptable salt of claim 1, wherein n is 1.

14. The compound or pharmaceutically acceptable salt of claim 1, wherein R₃ is —

CH₃.

22. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable excipient.

23. A method of treating breast cancer comprising administering to a subject a compound or pharmaceutically acceptable salt of claim 1.

24. The method according to claim 23, wherein said breast cancer is an ER-positive breast cancer.

2. (canceled)

3. (canceled)

4. A compound given by the following formula:

32. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 4 and a pharmaceutically acceptable excipient.

33. A method of treating breast cancer comprising administering to a subject a compound or pharmaceutically acceptable salt of claim 4.

34. The method according to claim 33, wherein said breast cancer is an ER-positive breast cancer.

5. (canceled)

6. A compound of Formula III or pharmaceutically acceptable salt thereof:

7. The compound or pharmaceutically acceptable salt of claim 6, wherein Y is selected from the group consisting of

35. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 6 and a pharmaceutically acceptable excipient.

36. A method of treating breast cancer comprising administering to a subject a compound or pharmaceutically acceptable salt of claim 6.

37. The method according to claim 36, wherein said breast cancer is an ER-positive breast cancer.

9. (canceled)

11. (canceled)

12. (canceled)

15. A compound selected from the group consisting of:

18. The compound of claim 15, having the following formula:

20. A compound of claim 15 having the following formula:

21. The compound of claim 20, having the following formula:

38. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 15 and a pharmaceutically acceptable excipient.

39. A method of treating breast cancer comprising administering to a subject a compound or pharmaceutically acceptable salt of claim 38.

40. The method according to claim 39, wherein said breast cancer is an ER-positive breast cancer.

41. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 20 and a pharmaceutically acceptable excipient.

42. A method of treating breast cancer comprising administering to a subject a compound or pharmaceutically acceptable salt of claim 20.

43. The method according to claim 42, wherein said breast cancer is an ER-positive breast cancer.

44. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 18 and a pharmaceutically acceptable excipient.

45. A method of treating breast cancer comprising administering to a subject a compound or pharmaceutically acceptable salt of claim 18.

46. The method according to claim 45, wherein said breast cancer is an ER-positive breast cancer.

16-17. -17. (canceled)

19. (canceled)

25-31. -31. (canceled)