Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof

• US 9,708,348 B2
• Filed: 10/02/2015
• Issued: 07/18/2017
• Est. Priority Date: 10/03/2014
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Tremblay, Martin R., Castro, Alfredo C., Evans, Catherine A.
• Primary Examiner(s): Murray, Jeffrey H
• Application Number:
  US14/874,328
• Publication Number:
  US 20160122365A1
• Time in Patent Office: 655 Days
• Field of Search: None
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07D 498/04 Ortho-condensed systems
• CPC Class Codes: C07D 513/04 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

Trisubstituted bicyclic heterocyclic compounds (e.g., chromenones and quinolines) and pharmaceutical compositions,that modulate kinase activity, including PI3 kinase activity, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Claims

1. A compound of Formula I′

or Formula II′

;

2. The compound of claim 1, which is a compound of Formula I′

;

3. The compound of claim 1, which is a compound of Formula II′

;

4. The compound of claim 1, wherein W_d is

5. The compound of claim 2, wherein the compound of Formula I′

is a compound of formula I;

6. The compound of claim 3, wherein the compound of Formula II′

is a compound of formula II;

7. The compound of claim 2, which is a compound of the formula:

formula;

8. The compound of claim 2, which is a compound of the formula:

9. The compound of claim 1, which is

10. The compound of claim 1, wherein W_d is

11. The compound of claim 1, wherein R^1f is NH₂.

12. The compound of claim 1, wherein R^2f,R^3f, and R^4f are hydrogen.

13. The compound of claim 1, wherein R^1a is C₁-C₈ alkyl.

14. The compound of claim 1, wherein R^1a is 5-14 membered heteroaryl containing one or more hetroatoms selected from the group consisting of N, O, and S.

15. The compound of claim 14, wherein R^1a is 5- or 6-membered heteroaryl containing one or more N heterotams.

16. The compound of claim 15, wherein the heteroaryl is optionally substitued with one or more C₁-C₈ alkyl.

17. The compound of claim 1, wherein R^1b, R^2b, R^3b, R^4b, and R^5b are hydrogen.

18. The compound of claim 1, wherein R^1c is methyl.

19. the compound of claim 1, which is

20. The compound of claim 1, which is

21. A pharmaceutically composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.