Aminopyrimidines useful as inhibitors of protein kinases

Abstract

The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

We claim: 
     
         1 . A compound of formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Ht is 
 
       
         
           
           
               
               
           
         
         wherein any substitutable carbon on Ht is independently and optionally substituted with —R 10 ; 
         Ring D is a 3-10 membered heterocyclyl; where said heterocyclyl contains 1-2 heteroatoms selected from O, N, or S; and wherein the heterocyclyl is independently and optionally substituted with 1-5-R 5 ; Ring D is bonded to the pyrimidine via a carbon atom; 
         Z 1  is N, CH, or CR 10 ; 
         R X  is H, halo, or C 1-6 alkyl, wherein the alkyl is independently and optionally substituted with 1-5 groups selected from halo, —CN, and —OR; 
         R Y  is H, halo, C 2-6 alkyl, or a 5-6 membered heterocyclyl ring containing 1-2 heteroatoms selected from O, N, or S; wherein said R Y  is independently and optionally substituted with 1-4 halo, CN, OR, or C 2-6 alkyl; 
         each R 10  is independently selected from C 1-6 alkyl, haloC 1-6 alkyl, halo, OR, C(═O)R, CO 2 R, COCOR, NO 2 , CN, S(O)R, SO 2 R, SR, N(R 4 ) 2 , CON(R 4 ) 2 , SO 2 N(R 4 ) 2 , OC(═O)R, N(R 4 )COR, or N(R 4 )CO 2 R; 
         each R 4  is independently selected from H, C 1-6 alkyl, or haloC 1-6 alkyl; 
         each R 5  is independently selected from halo, haloC 1-6 alkyl, or C 1-6 alkyl; and 
         each R is independently selected from H, C 1-6 alkyl, or haloC 1-6 alkyl. 
       
     
     
         2 . The compound according to  claim 1  wherein Ht is 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound according to  claim 2 , wherein R 10  is halo. 
     
     
         4 . The compound according to  claim 3 , wherein R 10  is fluoro. 
     
     
         5 . (canceled) 
     
     
         6 . The compound according to  claim 1 , wherein Z 1  is N. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The compound according to  claim 1 , wherein R X  is H. 
     
     
         11 . The compound according to  claim 1 , wherein R X  is methyl. 
     
     
         12 . The compound according to  claim 4 , wherein the halo is fluoro. 
     
     
         13 . The compound according to  claim 1 , wherein R Y  is halo or C 1-6  alkyl. 
     
     
         14 . The compound according to  claim 13 , wherein R Y  is methyl. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The compound according to  claim 1 , wherein said heterocyclyl is morpholinyl, piperidinyl, or piperazinyl. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The compound according to  claim 1 , wherein Ring D is a 6-membered heterocyclyl containing one oxygen atom. 
     
     
         25 . (canceled) 
     
     
         26 . The compound of  claim 1  selected from the following: 
       
         
           
           
               
               
           
         
       
     
     
         27 . A composition comprising a compound according to any one of  claim 1  or  26 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 
     
     
         28 - 46 . (canceled)