Compounds useful as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10464905-B2
Application number	US-201816113661-A
Country	US
Kind code	B2
Filing date	Aug 27, 2018
Priority date	Dec 16, 2015
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.

First claim

The invention claimed is:

1. A method of treating cancer in a patient in need thereof, the method comprising:
(a) detecting a cancer modulated by BTK signaling in a patient; and
(b) administering to the patient a therapeutically effective amount of a compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the cancer is selected from the group consisting of: lymphoma, leukemia, multiple myeloma, a B-cell malignancy and bone cancer.

3. The method of claim 2 , wherein the cancer is selected from: multiple myeloma, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, Burkitt lymphoma, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, B-cell prolymphocyte leukemia, and hairy cell leukemia.

4. The method of claim 1 , wherein the cancer has one or more BTK inhibitor resistance mutations.

5. The method of claim 4 , wherein the one or more BTK inhibitor resistance mutations is selected from the group consisting of C481S, C481Y, C481R, and C481F.

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

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.

16. A method for treating a cancer modulated by BTK signaling in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17. The method of claim 16 , wherein the cancer is selected from the group consisting of: lymphoma, leukemia, multiple myeloma, a B-cell malignancy and bone cancer.

18. The method of claim 17 , wherein the cancer is selected from: multiple myeloma, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, Burkitt lymphoma, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, B-cell prolymphocyte leukemia, and hairy cell leukemia.

19. The method of claim 16 , wherein the cancer has one or more BTK inhibitor resistance mutations.

20. The method of claim 19 , wherein the one or more BTK inhibitor resistance mutations is selected from the group consisting of C481S, C481Y, C481R, and C481F.

21. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

22. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

23. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

24. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

25. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

26. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

27. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

28. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

29. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

Assignees

• Loxo Oncology Inc

Inventors

• Guisot Nicolas

Classifications

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D405/08

  linked by a carbon chain containing alicyclic rings · CPC title

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title