Aryl ethers and uses thereof

Abstract

The present disclosure relates to HIF-2α inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2α scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.

1 - 64 . (canceled) 
     
     
         65 . A compound having one of the formulae: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof,
 wherein: 
 R 1  is aryl or heteroaryl; 
 R 4  is nitro, halo, cyano, alkyl, sulfinyl, sulfonamide, sulfonyl or sulfoximinyl; 
 R 5  is hydrogen; halo or alkyl; and 
 R 8  is hydrogen, hydroxy, alkoxy, alkylamino or amino. 
 
     
     
         66 . The compound of  claim 65 , wherein R 1  is monocyclic aryl or monocyclic heteroaryl. 
     
     
         67 . The compound of  claim 66 , wherein R 1  is phenyl or pyridyl. 
     
     
         68 . The compound of  claim 67 , wherein said phenyl or pyridyl is substituted with one or more substituents selected from the group consisting of halo, alkyl, alkoxy, and cyano. 
     
     
         69 . The compound of  claim 65 , wherein R 1  is bicyclic heteroaryl having at least one N atom. 
     
     
         70 . The compound of  claim 65 , wherein R 4  is cyano, fluoroalkyl, sulfonamide, sulfonyl, sulfinyl or sulfoximinyl. 
     
     
         71 . The compound of  claim 65 , wherein R 5  is hydrogen or alkyl. 
     
     
         72 . The compound of  claim 71 , wherein R 5  is C1-C4 alkyl. 
     
     
         73 . The compound of  claim 66 , wherein R 1  is phenyl or monocylic heteroaryl and R 8  is hydroxy or amino. 
     
     
         74 . The compound of  claim 69 , wherein R 8  is hydroxy or amino.