Heterocyclic Inhibitors of Glutaminase

Abstract

The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel heterocyclic compounds of the invention.

1 - 71 . (canceled) 
     
     
         72 . A method of making a compound having the structure of formula D: 
       
         
           
           
               
               
           
         
         comprising combining a compound having the structure of formula F: 
       
       
         
           
           
               
               
           
         
         with BrZn(CH 2 ) 4 CN solution and a NiCl 2 (dppp) catalyst, thereby forming a compound of formula D. 
       
     
     
         73 . The method of  claim 72 , further comprising combining a compound having the structure of formula G: 
       
         
           
           
               
               
           
         
         with a compound having the structure of formula H: 
       
       
         
           
           
               
               
           
         
         to form a mixture, then treating the mixture with diisopropylethylamine and propylphosphonic anhydride, thereby forming a compound of formula F. 
       
     
     
         74 . The method of  claim 73 , wherein combining the compound having the structure of formula G with the compound having the structure of formula H occurs in the presence of dimethylformamide. 
     
     
         75 . A method of making a compound having the structure of formula D: 
       
         
           
           
               
               
           
         
         comprising combining a compound having the structure of formula K: 
       
       
         
           
           
               
               
           
         
         with Pd(OH) 2 /C under a hydrogen atmosphere, thereby forming the compound of formula D. 
       
     
     
         76 . The method of  claim 75 , further comprising combining a compound having the structure of formula L: 
       
         
           
           
               
               
           
         
         wherein X is selected from Cl, Br, and I; 
         with pent-4-ynenitrile, thereby forming the compound of formula K. 
       
     
     
         77 . The method of  claim 76 , further comprising combining a compound having the structure of formula M: 
       
         
           
           
               
               
           
         
         with 3-trifluoromethylphenylacetyl chloride, thereby forming the compound of formula L.