Chemical compounds, compositions and methods for kinase modulation

• US 9,181,221 B2
• Filed: 11/20/2013
• Issued: 11/10/2015
• Est. Priority Date: 05/21/2010
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Ren, Pingda, Liu, Yi, Li, Liansheng, Chan, Katrina, Castro, Alfredo C., Evans, Catherine A.
• Primary Examiner(s): Murray, Jeffrey H
• Application Number:
  US14/085,660
• Publication Number:
  US 20140088099A1
• Time in Patent Office: 720 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• 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: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 473/16 two nitrogen atoms
• CPC Class Codes: C07D 473/32 Nitrogen atom
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Substituted isoquinolinone compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, 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 (Ib):

2. The compound of claim 1, wherein R³ is aryl.

3. The compound of claim 2, wherein the aryl is phenyl.

4. The compound of claim 3, wherein R³ is

5. The compound of claim 1, wherein R³ is alkenyl.

6. The compound of claim 5, wherein the alkenyl is ethenyl.

7. The compound of claim 1, wherein R³ is a heteroatom selected from N, S, and O, and the heteroatom has a covalent bond directly to heterocyclyl.

8. The compound of claim 1, wherein B is:

9. The compound of claim 8, wherein q is 0.

10. The compound of claim 8, wherein R¹ is hydrogen.

11. The compound of claim 1, wherein Y is —

N(R⁹)—

.

12. The compound of claim 1, wherein X is —

(CH(R⁹))_z—

.

13. The compound of claim 12, wherein z is 1.

14. The compound of claim 1, wherein R⁹ is hydrogen or alkyl.

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

16. The compound of claim 15, wherein the compound is

17. A pharmaceutical composition comprising a compound according to claim 1 and one or more pharmaceutically acceptable excipients.

18. A method of inhibiting a phosphoinositide 3-kinase (PI3K) in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1.