Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors

• US 8,377,946 B1
• Filed: 06/21/2012
• Issued: 02/19/2013
• Est. Priority Date: 12/30/2011
• Status: Active Grant

• Current Assignee: Pharmacyclics LLC (Abbvie Incorporated)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated)
• Inventors: Chen, Wei, Loury, David J.
• Primary Examiner(s): Moore, Susanna
• Application Number:
  US13/529,911
• Time in Patent Office: 243 Days
• Field of Search: 544/262, 514/262.1
• US Class Current: 514/262.1
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• 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 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Disclosed herein are compounds of Formula (II) that form covalent bonds with Bruton'"'"'s tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Claims

1. A compound having the structure of Formula (II):

2. The compound of claim 1, wherein Y is substituted or unsubstituted phenylene;

and Z is NR₄C(═

O).

3. The compound of claim 2, wherein each R₃ is independently —

F, —

Cl, —

CH₃, or —

OCH₃.

4. The compound of claim 3, wherein R₁ and R₂ are each independently substituted or unsubstituted C₁-C₄alkyl, or substituted or unsubstituted C₃-C₆cycloalkyl.

5. The compound of claim 4, wherein R₄ is —

CH₃.

6. The compound of claim 4, wherein R₄ is H.

7. The compound of claim 1, wherein Y is substituted or unsubstituted heteroarylene;

and Z is NR₄C(═

O).

8. The compound of claim 7, wherein each R₃ is independently —

F, —

Cl, —

CH₃, or —

OCH₃.

9. The compound of claim 8, wherein R₁ and R₂ are each independently substituted or unsubstituted C₁-C₄alkyl, or substituted or unsubstituted C₃-C₆cycloalkyl.

10. The compound of claim 9, wherein R₄ is —

CH₃.

19. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

11. A compound having the structure of Formula (III):

12. The compound of claim 11, wherein Y is substituted or unsubstituted phenylene;

and Z is NR₄C(═

O).

13. The compound of claim 12, wherein each R₃ is independently —

F, —

Cl, —

CH₃, or —

OCH₃.

14. The compound of claim 13, wherein R₄ is —

CH₃.

15. The compound of claim 13, wherein R₄ is H.

16. The compound of claim 11, wherein Y is substituted or unsubstituted heteroarylene;

and Z is NR₄C(═

O).

17. The compound of claim 16, wherein each R₃ is independently —

F, —

Cl, —

CH₃, or —

OCH₃.

18. The compound of claim 17, wherein R₄ is —

CH₃.