Compounds that inhibit MCL-1 protein

• US 10,300,075 B2
• Filed: 03/28/2018
• Issued: 05/28/2019
• Est. Priority Date: 03/30/2017
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Brown, Sean P., Li, Kexue, Li, Yunxiao, Stec, Markian M.
• Primary Examiner(s): Habte, Kahsay
• Application Number:
  US15/938,001
• Publication Number:
  US 20180289720A1
• Time in Patent Office: 426 Days
• Field of Search: 51421109
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07D 498/08 Bridged systems

Abstract

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I,

or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Claims

1. A compound, wherein the compound is selected from:

2. The compound of claim 1 or the pharmaceutically acceptable salt thereof.

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

4. The compound of claim 1, wherein the compound is

5. A pharmaceutical composition comprising the compound of claim 4 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

6. The compound of claim 1, wherein the compound is

7. A pharmaceutical composition comprising the compound of claim 6 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

8. The compound of claim 1, wherein the compound is

9. A pharmaceutical composition comprising the compound of claim 8 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

10. The compound of claim 1, wherein the compound is

11. A pharmaceutical composition comprising the compound of claim 10 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

12. The compound of claim 1, wherein the compound is

13. A pharmaceutical composition comprising the compound of claim 12 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

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

15. A pharmaceutical composition comprising the compound of claim 14 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

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

17. A pharmaceutical composition comprising the compound of claim 16 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

18. The compound of claim 1, wherein the compound is

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

20. The compound of claim 1, wherein the compound is

21. A pharmaceutical composition comprising the compound of claim 20 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

22. The compound of claim 1, wherein the compound is

23. A pharmaceutical composition comprising the compound of claim 22 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

24. The compound of claim 1, wherein the compound is

25. A pharmaceutical composition comprising the compound of claim 24 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

26. The compound of claim 1, wherein the compound is

27. A pharmaceutical composition comprising the compound of claim 26 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

28. The compound of claim 1, wherein the compound is

29. A pharmaceutical composition comprising the compound of claim 28 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

30. The compound of claim 1, wherein the compound is

31. A pharmaceutical composition comprising the compound of claim 30 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

32. The compound of claim 1, wherein the compound is

33. A pharmaceutical composition comprising the compound of claim 32 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

34. The compound of claim 1, wherein the compound is

35. A pharmaceutical composition comprising the compound of claim 34 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

36. The compound of claim 1, wherein the compound is

37. A pharmaceutical composition comprising the compound of claim 36 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

38. The compound of claim 1, wherein the compound is

39. A pharmaceutical composition comprising the compound of claim 38 or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.