Compounds and methods for kinase modulation, and indications therefor

Abstract

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

1 . (canceled) 
     
     
         2 . A compound of formula (Ia): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         L 1  is a bond or —N(H)C(O)—; 
         each R 1  is R 16 ; 
         R 2  is hydrogen or halogen; 
         R 3  is lower alkyl or phenyl substituted with one or more substituents selected from the group consisting of fluoro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, and fluoro substituted lower alkylthio; 
         R 4  is hydrogen; 
         m is 0, 1, 2, or 3; 
         Ar is 
       
       
         
           
           
               
               
           
         
         each X is independently N or CH, provided that at least one and no more than 2 of X in any ring is N; 
         Y is NH, O, or S; 
         each R 16  is independently lower alkyl or heteroaryl, wherein the heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, —NH 2 , —CN, —NO 2 , —C(O)—OH, —S(O) 2 —NH 2 , —C(O)—NH 2 , —O—R 18 , —S—R 18 , —N(R 19 )—R 18 , —N(R 19 )—C(O)—R 18 , —N(R 19 )—S(O) 2 —R 18 , —S(O) 2 —R 18 , —C(O)—R 18 , —C(O)—O—R 18 , —C(O)—N(R 19 )—R 18 , —S(O) 2 —N(R 19 )—R 18 , halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino; 
         R 18  is lower alkyl; and 
         R 19  at each occurrence is hydrogen or lower alkyl. 
       
     
     
         3 . The compound of  claim 2 , wherein R 2  is hydrogen. 
     
     
         4 . The compound of  claim 2 , wherein R 2  is halogen. 
     
     
         5 . The compound of  claim 2 , wherein R 3  is phenyl substituted with one or more fluoro. 
     
     
         6 . A pharmaceutical composition comprising a compound of  claim 2  and a pharmaceutically acceptable carrier or excipient.