Details for Patent: 7,732,454
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Title: | Inhibitors of Bruton's tyrosine kinase |
Abstract: | Disclosed herein are imidazo[1,5-f][1,2,4]triazine compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). The imidazo[1,5-f][1,2,4]triazine compounds described are irreversible inhibitors of Btk. Methods for the preparation of the imidazo[1,5-f][1,2,4]triazine compounds are disclosed. Also disclosed are pharmaceutical compositions that include the imidazo[1,5-f][1,2,4]triazine compounds. Methods of using the imidazo[1,5-f][1,2,4]triazine 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. |
Inventor(s): | Verner; Erik (San Mateo, CA) |
Assignee: | Pharmacyclics, Inc. (Sunnyvale, CA) |
Filing Date: | Mar 28, 2007 |
Application Number: | 11/692,870 |
Claims: | 1. A compound of Formula (E) having the structure: ##STR00076## wherein: L.sub.a is O or S; Ar is an unsubstituted phenyl; Y is a 4-, 5-, 6-, or 7-membered cycloalkyl ring, or Y is a 4-, 5-, 6-, or 7-membered monocyclic nitrogen-containing heterocycloalkyl ring; Z is C(.dbd.O), OC(.dbd.O), NHC(.dbd.O), S(.dbd.O).sub.x, or NHS(.dbd.O).sub.x, where x is 2; R.sub.8 is H; R.sub.7 is H, unsubstituted C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.6alkoxyalkyl, C.sub.1-C.sub.8alkylaminoalkyl, or C.sub.1-C.sub.4alkyl(phenyl); or R.sub.7 and R.sub.8 taken together form a bond; R.sub.6 is H, unsubstituted C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.6alkoxyalkyl, C.sub.1-C.sub.8alkylaminoalkyl, or C.sub.1-C.sub.4alkyl(phenyl); or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein L.sub.a is O. 3. The compound of claim 2, wherein: Z is C(.dbd.O), NHC(.dbd.O), or S(.dbd.O).sub.2. 4. The compound of claim 3, wherein: each of R.sub.7 and R.sub.8 is H; or R.sub.7 and R.sub.8 taken together form a bond. 5. The compound of claim 3, wherein: each of R.sub.6 and R.sub.8 is H. 6. A pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable excipient. 7. A pharmaceutical composition comprising a compound of claim 2, and a pharmaceutically acceptable excipient. 8. A pharmaceutical composition comprising a compound of claim 3, and a pharmaceutically acceptable excipient. 9. A pharmaceutical composition comprising a compound of claim 4, and a pharmaceutically acceptable excipient. 10. A pharmaceutical composition comprising a compound of claim 5, and a pharmaceutically acceptable excipient. 11. The compound of claim 1 having the structure: ##STR00077## 12. A pharmaceutical composition comprising a compound of claim 11, and a pharmaceutically acceptable excipient. |