Purine inhibitors of protein kinases, G proteins and polymerases

Abstract

The present invention relates to purine analogs that inhibit, inter alia, protein kinases, G-proteins and polymerases. In addition, the present invention relates to methods of using such purine analogs to inhibit protein kinases, G-proteins, polymerases and other cellular processes and to treat cellular proliferative diseases.

1 - 25 . (cancelled)  
     
     
         26 . A method of affinity purification of a cyclin-dependent kinase from a cellular extract, wherein said cyclin-dependent kinase is present in a complex which is a member selected from the group consisting of cdc2/cyclin B, CDK1/cyclin B, CDK2/cyclin E, CDK-5/p25 and CDK2/cyclin A, said method comprising contacting said cellular extract with a compound that is immobilized, said compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2 , R 3 , R 4 . R 5  are independently members selected from the group consisting of H, C 1 -C 8  straight-chain, branched-chain, saturated and unsaturated alkyl, C 1 -C 8  straight-chain, branched-chain, saturated and unsaturated substituted alkyl, aryl and substituted aryl.  
 
     
     
         27 . The method according to  claim 26 , wherein said compound has the formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is a member selected from the group consisting of H and NH 2 ;  
 R 2  is a member selected from the group consisting of H, CO 2 H, OH and halogen; and  
 R 3  is a member selected from the group consisting of CO 2 H, NH 2  and halogen.  
 
     
     
         28 . The method according to  claim 26 , wherein said compound has a formula that is a member selected from:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         29 . A method of synchronizing cells in cell culture in a member selected from G1 and late G2/early prophase, said method comprising contacting said cells with an amount of a first compound effective to synchronize said cells, said compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2 , R 3 , R 4 . R 5  are independently members selected from the group consisting of H, C 1 -C 8  straight-chain, branched-chain, saturated and unsaturated alkyl, C 1 -C 8  straight-chain, branched-chain, saturated and unsaturated substituted alkyl, aryl and substituted aryl.  
 
     
     
         30 . The method according to  claim 29 , wherein said first compound has the formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is a member selected from the group consisting of H and NH 2 ;  
 R 2  is a member selected from the group consisting of H, CO 2 H, OH and halogen; and  
 R 3  is a member selected from the group consisting of CO 2 H, NH 2  and halogen.  
 
     
     
         31 . The method according to  claim 29 , wherein said compound has a formula that is a member selected from:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         32 . The method according to  claim 29 , further comprising contacting said cells with an amount of a second compound effective to synchronize said cells.