.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 9,139,591

« Back to Dashboard

Details for Patent: 9,139,591

Title:Inhibitors of bruton's tyrosine kinase
Abstract: Described herein are irreversible kinase inhibitor compounds exemplified by the following structure Formula (A2): ##STR00001## methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of a B cell proliferative disorder or a mast cell proliferative disorder.
Inventor(s): Honigberg; Lee (San Francisco, CA), Verner; Erik J. (Belmont, CA), Buggy; Joseph J. (Mountain View, CA), Loury; David J. (San Jose, CA), Chen; Wei (Fremont, CA)
Assignee: PHARMACYCLICS LLC (Sunnyvale, CA)
Filing Date:Jul 06, 2012
Application Number:13/543,394
Claims:1. A compound of Formula (A5) having the structure: ##STR00125## wherein: R.sub.1 is H, L.sub.2-(substituted or unsubstituted alkyl), L.sub.2-(substituted or unsubstituted cycloalkyl), L.sub.2-(substituted or unsubstituted alkenyl), L.sub.2-(substituted or unsubstituted cycloalkenyl), L.sub.2-(substituted or unsubstituted heterocycle), L.sub.2-(substituted or unsubstituted heteroaryl), or L.sub.2-(substituted or unsubstituted aryl), where L.sub.2 is a bond, O, S, --S(.dbd.O), --S(.dbd.O).sub.2, C(.dbd.O), -(substituted or unsubstituted C.sub.1-C.sub.6 alkyl), or -(substituted or unsubstituted C.sub.2-C.sub.6 alkenyl); R.sub.2 and R.sub.3 are independently selected from H, lower alkyl and substituted lower alkyl; R.sub.4 is L.sub.3-X-L.sub.4-G, wherein, L.sub.3 is optional, and when present is a bond, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl; X is optional, and when present is a bond, O, --C(.dbd.O), S, --S(.dbd.O), --S(.dbd.O).sub.2, --NH, --NR.sub.9, --NHC(O), --C(O)NH, --NR.sub.9C(O), --C(O)NR.sub.9, --S(.dbd.O).sub.2NH, --NHS(.dbd.O).sub.2, --S(.dbd.O).sub.2NR.sub.9--, --NR.sub.9S(.dbd.O).sub.2, --OC(O)NH--, --NHC(O)O--, --OC(O)NR.sub.9--, --NR.sub.9C(O)O--, --CH.dbd.NO--, --ON.dbd.CH--, --NR.sub.10C(O)NR.sub.10--, heteroaryl, aryl, --NR.sub.10C(.dbd.NR.sub.11)NR.sub.10--, --NR.sub.10C(.dbd.NR.sub.11)--, --C(.dbd.NR.sub.11)NR.sub.10--, --OC(.dbd.NR.sub.11)--, or --C(.dbd.NR.sub.11)O--; L.sub.4 is optional, and when present is a bond, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle; or L.sub.3, X and L.sub.4 taken together form a nitrogen containing heterocyclic ring; G is ##STR00126## wherein, R.sub.6, R.sub.7 and R.sub.8 are independently selected from among H, lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl; R.sub.5 is H, halogen, -L.sub.6-(substituted or unsubstituted C.sub.1-C.sub.3 alkyl), -L.sub.6-(substituted or unsubstituted C.sub.2-C.sub.4 alkenyl), -L.sub.6-(substituted or unsubstituted heteroaryl), or -L.sub.6-(substituted or unsubstituted aryl), wherein L.sub.6 is a bond, O, S, --S(.dbd.O), S(.dbd.o).sub.2, NH, C(O), --NHC(O)O, --OC(O)NH, --NHC(O), or --C(O)NH; each R.sub.9 is independently selected from among H, substituted or unsubstituted lower alkyl, and substituted or unsubstituted lower cycloalkyl; each R.sub.10 is independently H, substituted or unsubstituted lower alkyl, or substituted or unsubstituted lower cycloalkyl; or two R.sub.10 groups can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring; or R.sub.9 and R.sub.10 can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring; or each R.sub.11is independently selected from H, --S(.dbd.O).sub.2R.sub.8, --S(.dbd.O).sub.2NH.sub.2, --C(O)R.sub.8, --CN, --NO.sub.2, heteroaryl, or heteroalkyl; or pharmaceutically acceptable salts thereof.

2. The compound of claim 1, wherein R.sub.2 and R.sub.3 are H.

3. The compound of claim 2, wherein R.sub.1 is L.sub.2-(substituted or unsubstituted heteroaryl), or L.sub.2-(substituted or unsubstituted aryl).

4. The compound of claim 3 having the structure ##STR00127## wherein each R.sub.a is independently H, halogen, --CF.sub.3, --CN, --NO.sub.2, OH, NH.sub.2, -L.sub.a-(substituted or unsubstituted alkyl), or -L.sub.a-(substituted or unsubstituted alkenyl), wherein L.sub.a is a bond, O, S, --S(.dbd.O), --S(.dbd.O).sub.2, NH, C(O), CH.sub.2, --NHC(O)O, --NHC(O), or --C(O)NH.

5. The compound of claim 4, wherein L.sub.3, X and L.sub.4 taken together form a nitrogen containing heterocyclic ring.

6. The compound of claim 5, wherein G is ##STR00128##

7. The compound of claim 6, wherein R.sub.6, R.sub.7, and R.sub.8 are H.

8. The compound of claim 6, wherein R.sub.7 and R.sub.8 are H; and R.sub.6 is selected from lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl.

9. The compound of claim 8, wherein R.sub.6 is substituted lower alkyl.

10. The compound of claim 9, wherein lower alkyl is substituted with a disubstituted amino group.

11. The compound of claim 6, wherein R.sub.6 and R.sub.8 are H; and R.sub.7 is selected from lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl.

12. The compound of claim 11, wherein R.sub.7 is substituted lower alkyl.

13. The compound of claim 12, wherein lower alkyl is substituted with a disubstituted amino group.

14. The compound of claim 5, wherein G is ##STR00129##

15. The compound of claim 14, wherein R.sub.6 is H.

16. The compound of claim 14, wherein R.sub.6 is selected from lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl.

17. The compound of claim 16, wherein R.sub.6 is substituted lower alkyl.

18. The compound of claim 17, wherein lower alkyl is substituted with a disubstituted amino group.

19. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, and a pharmaceutically acceptable excipient.

20. The pharmaceutical composition of claim 19 that is formulated for a route of administration selected from oral administration, parenteral administration, buccal administration, nasal administration, topical administration, or rectal administration.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc