Pyrrolopyrimidine ITK inhibitors for treating inflammation and cancer

• US 10,316,038 B2
• Filed: 01/25/2018
• Issued: 06/11/2019
• Est. Priority Date: 01/25/2017
• Status: Active Grant

• Current Assignee: Aclaris Therapeutics, Inc. (Confluence Life Sciences, Inc.)
• Original Assignee: Aclaris Therapeutics, Inc. (Confluence Life Sciences, Inc.)
• Inventors: Jacobsen, Eric Jon, Blinn, James Robert, Springer, John Robert, Hockerman, Susan Landis, Anderson, David Randolph
• Primary Examiner(s): Rahmani, Niloofar
• Application Number:
  US15/880,385
• Publication Number:
  US 20180208594A1
• Time in Patent Office: 502 Days
• Field of Search: 514300, 514303, 546119, 546121
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I):

wherein R¹, R², and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Claims

1. A compound, of Formula (I):

2. The compound of claim 1, wherein the compound has structural Formula (II):

3. The compound of claim 2, wherein

R¹ is phenyl, optionally substituted with one R³ substituent;

and

R³ is chosen from hydrogen, cyano, —

OC_1-4alkyl, and halo.

4. The compound of claim 2, wherein

R¹ is heteroaryl, and may be optionally substituted with one R³ substituent;

and R³ is chosen from hydrogen, cyano, —

OC_1-4alkyl, and halo.

5. The compound of claim 4, wherein R¹ is pyridyl.

6. The compound of claim 2, wherein:

R^4b is chosen from hydrogen, —

C_1-4alkyl, heteroaryl, —

OC_1-4alkyl, haloalkyl, haloalkoxy,and halo.

7. The compound of claim 2, wherein R^4c is hydrogen.

8. The compound of claim 1, wherein the compound has structural Formula (III):

9. The compound of claim 8, wherein

R¹ is phenyl, optionally substituted with one R³ substituent;

and

R³ is chosen from hydrogen, cyano, —

OC_1-4alkyl, and halo.

10. The compound of claim 8, wherein

R¹ is heteroaryl, and may be optionally substituted with one R³ substituent;

and

R³ is chosen from hydrogen, cyano, —

OC_1-4alkyl, and halo.

11. The compound of claim 10, wherein R¹ is pyridyl.

12. The compound of claim 8, wherein:

R^4b is chosen from hydrogen, —

C_1-4alkyl, heteroaryl, —

OC_1-4alkyl, haloalkyl, haloalkoxy, and halo.

13. The compound of claim 8, wherein R^4c is hydrogen.

14. The compound of claim 1, wherein the compound has structural Formula (IV):

15. The compound of claim 1, wherein the compound has structural Formula (V):

16. The compound of claim 1, wherein the compound has structural Formula (VI):

17. The compound of claim 1, wherein the compound has structural Formula (VII):

18. The compound of claim 1, wherein the compound has structural Formula (VIII):

19. The compound of claim 1, wherein the compound has structural Formula (IX):

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

21. The compound of claim 14, wherein the compound is selected from

22. The compound of claim 15, wherein the compound is selected from

23. The compound of claim 16, wherein the compound is selected from

24. The compound of claim 17, wherein the compound is selected from

25. The compound of claim 18, wherein the compound is selected from

26. The compound of claim 19, wherein the compound is selected from

27. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.