Salts of heterocyclic modulators of hif activity for treatment of disease

Abstract

The present disclosure relates to salts of heterocyclic compounds and methods that inhibit HIF pathway activity. The compounds are designed to treat or prevent cancer and other hypoxia-mediated diseases.

1 .- 29 . (canceled) 
     
     
         30 . The compound that is 5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole hydrochloride, wherein:
 the compound displays an endothermic peak in differential scanning calorimetry with an onset temperature of 164.0° C.; and/or   the compound is characterized by an x-ray powder diffraction pattern as shown in  FIG. 12 ; and/or   the compound is characterized by a TGA-MS profile showing weight loss of ˜6.5% from 118.4° C. to 196.4° C.   
     
     
         31 . The compound that is 5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole methanesulfonate, wherein:
 the compound is characterized by an x-ray powder diffraction pattern as shown in  FIG. 14 ; and/or   the compound is characterized by a TGA-MS profile showed weight loss of ˜1.7% from 91.5° C. to 193.1° C. and 3.8% from 93.1 to 216.6° C.; and/or   the compound is characterized by a decomposition temperature of ˜190° C.   
     
     
         32 . A method of preparing a compound of structural Formula VI 
       
         
           
           
               
               
           
         
         wherein X is chosen from chloride, mesylate, and besylate, said method comprising: contacting a compound of structural formula 
       
       
         
           
           
               
               
           
         
         with an acid chosen from hydrochloric acid, benzenesulfonic acid, and methanesulfonic acid to form a compound of structural formula VI. 
       
     
     
         33 . The method of  claim 32 , wherein the acid is hydrochloric acid. 
     
     
         34 . The method of  claim 32 , wherein the acid is benzenesulfonic acid. 
     
     
         35 . The method of  claim 32 , wherein the acid is methanesulfonic acid. 
     
     
         36 . The method of  claim 32 , further comprising collecting the compound of structural formula VI. 
     
     
         37 . The method of  claim 36 , further comprising combining the collected compound of structural formula VI with a pharmaceutically acceptable carrier. 
     
     
         38 . A pharmaceutical composition comprising the compound of  claim 30  together with a pharmaceutically acceptable carrier. 
     
     
         39 . A pharmaceutical composition comprising the compound of  claim 31  together with a pharmaceutically acceptable carrier.