Inhibitors of bruton's tyrosine kinase

Abstract

Disclosed herein are amido compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. 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.

1 . A compound according to formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         A is 
       
       
         
           
           
               
               
           
         
         Hy is 2-pyridyl substituted with 1-5 groups independently selected from R 4 , or 
         Hy is imidazolyl, thiazolyl, oxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, isothiazolyl, or tetrazolyl, each of which substituted with 1-2 groups independently selected from R 4 ; 
         each R 1  and R 2  is independently H, alkyl, or CN; or R 1  and R 2  together form a bond; 
         R 3  is independently H, alkyl, CN, or cycloalkyl; 
         each R 4  is independently H, halo, hydroxyl, CN, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted alkoxy, substituted or unsubstituted amido, substituted or unsubstituted sulfonyl, substituted or unsubstituted carboxy, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or two adjacent R 4 s connect together with Hy to form a bicyclic ring; 
         each n is independently 0, 1, or 2; and 
         p is 0, 1 or 2; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 - 20 . (canceled)