Heterocyclic glutaminase inhibitors

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 - 82 . (canceled) 
     
     
         83 . A method of making a compound having the structure of formula Cg: 
       
         
           
           
               
               
           
         
         or a salt thereof; 
         comprising combining a compound having the structure of formula Ag: 
       
       
         
           
           
               
               
           
         
         with a compound having the structure of formula Bg: 
       
       
         
           
           
               
               
           
         
         under amide coupling conditions, thereby forming the compound of formula Cg; 
         wherein Ar 1  and Ar 2  each independently represent optionally substituted aryl. 
       
     
     
         84 . The method of  claim 83 , wherein the amide coupling conditions comprise a peptide coupling reagent. 
     
     
         85 . The method of  claim 84 , wherein the peptide coupling reagent is a carbodiimide. 
     
     
         86 . The method of  claim 85 , wherein the peptide coupling agent is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI). 
     
     
         87 . The method of  claim 84 , wherein the amide coupling conditions further comprise hydroxybenzotriazole (HOBT). 
     
     
         88 . The method of  claim 85 , wherein the amide coupling conditions further comprise hydroxybenzotriazole (HOBT). 
     
     
         89 . The method of  claim 86 , wherein the amide coupling conditions further comprise hydroxybenzotriazole (HOBT). 
     
     
         90 . The method of  claim 83 , wherein Ar 1  is phenyl. 
     
     
         91 . The method of  claim 83 , wherein Ar 2  is optionally substituted phenyl. 
     
     
         92 . The method of  claim 83 , wherein Ar 2  is phenyl optionally substituted with halogen. 
     
     
         93 . The method of  claim 83 , wherein Ar 2  is phenyl. 
     
     
         94 . The method of  claim 83 , further comprising:
 (i) combining a carboxyl-activating agent with a compound, or salt thereof, having the structure of formula Dg   
       
         
           
           
               
               
           
         
         to form a first reaction mixture; and 
         (ii) combining the first reaction mixture with the compound of formula Cg to form a compound of formula Eg: 
       
       
         
           
           
               
               
           
         
         wherein: 
         n is an integer from 1 to 2; 
         R 1  and R 2  are each independently alkyl; or 
         R 1  and R 2  taken together with the intervening nitrogen atom form an optionally substituted heterocycloalkyl ring. 
       
     
     
         95 . The method of  claim 94 , wherein the carboxyl-activating agent is N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC). 
     
     
         96 . The method of  claim 94 , wherein R 1  and R 2  taken together with the intervening nitrogen atom form an optionally substituted heterocycloalkyl ring. 
     
     
         97 . The method of  claim 96 , wherein R 1  and R 2  taken together with the intervening nitrogen atom form an optionally substituted morpholine, piperidine, or piperazine ring.