Human protein tyrosine phosphatase inhibitors and methods of use

Abstract

The present disclosure relates to compounds effective as human protein tyrosine phosphatase beta (HPTP-β) inhibitors thereby regulating angiogenesis. The present disclosure further relates to compositions comprising said human protein tyrosine phosphatase beta (HPTP-β) inhibitors, and to methods for regulating angiogenesis.

1 .- 63 . (canceled) 
     
     
         64 . A process for preparing Compound No. 91: 
       
         
           
           
               
               
           
         
       
       comprising:
 reacting an amine having the formula: 
 
       
         
           
           
               
               
           
         
         with a sulfur trioxide source. 
       
     
     
         65 . The process of  claim 64 , wherein the sulfur trioxide source is sulfur trioxide pyridine. 
     
     
         66 . The process of  claim 64 , wherein the amine is reacted with the sulfur trioxide source in the presence of a solvent. 
     
     
         67 . The process of  claim 66 , wherein the solvent is a polar aprotic solvent. 
     
     
         68 . The process of  claim 64 , wherein the amine 
       
         
           
           
               
               
           
         
       
       is prepared by reducing a nitro compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         69 . The process of  claim 68 , wherein the reducing occurs in the presence of a palladium catalyst and hydrogen gas. 
     
     
         70 . The process of  claim 69 , wherein the palladium catalyst is palladium on carbon. 
     
     
         71 . The process of  claim 68 , wherein the nitro compound 
       
         
           
           
               
               
           
         
       
       is prepared by reacting a thiophene amine having the formula: 
       
         
           
           
               
               
           
         
       
       with a methyl carbamate having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         72 . The process of  claim 71 , wherein the thiophene amine is reacted with the methyl carbamate in the presence of a coupling agent. 
     
     
         73 . The process of  claim 72 , wherein the coupling agent is HOBt. 
     
     
         74 . The process of  claim 71 , wherein the thiophene amine 
       
         
           
           
               
               
           
         
       
       is prepared by reacting a bromide having the formula: 
       
         
           
           
               
               
           
         
       
       with thiophene-2-carbothioamide. 
     
     
         75 . The process of  claim 74 , wherein the bromide is reacted with thiophene-2-carbothioamide in the presence of a solvent. 
     
     
         76 . The process of  claim 75 , wherein the solvent is a polar, aprotic solvent. 
     
     
         77 . The process of  claim 76 , wherein the solvent is acetonitrile. 
     
     
         78 . The process of  claim 74 , wherein the bromide 
       
         
           
           
               
               
           
         
       
       is prepared by reacting a diazo compound having the formula: 
       
         
           
           
               
               
           
         
       
       with a brominating agent. 
     
     
         79 . The process of  claim 78 , wherein the brominating agent is hydrobromic acid. 
     
     
         80 . The process of  claim 78 , wherein the diazo compound 
       
         
           
           
               
               
           
         
       
       is prepared from an acid having a formula: 
       
         
           
           
               
               
           
         
       
     
     
         81 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         82 . The compound of  claim 81 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         83 . The compound of  claim 81 , wherein the compound is