Compounds that inhibit MCL-1 protein

Patent metadata

Field	Value
Publication number	US-10300075-B2
Application number	US-201815938001-A
Country	US
Kind code	B2
Filing date	Mar 28, 2018
Priority date	Mar 30, 2017
Publication date	May 28, 2019
Grant date	May 28, 2019

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.

First claim

The invention claimed is:

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

or the stereoisomer thereof, the pharmaceutically acceptable salt thereof, or the pharmaceutically acceptable salt of the stereoisomer thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharmaceutically acceptable salt thereof.

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

or the pharm

Assignees

• Amgen Inc

Inventors

• Brown Sean P
• Li Kexue
• Li Yunxiao
• Stec Markian M

Classifications

• A61K31/553 Primary

  having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07D498/08 Primary

  Bridged systems · CPC title