Aryl hydrocarbon receptor antagonists and uses thereof

Abstract

The disclosure relates to aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as methods of expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expanded hematopoietic stem cells. The disclosure further provides methods of synthesizing aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as kits containing aryl hydrocarbon receptor antagonists that can be used for the expansion of hematopoietic stem cells.

1 . A compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and salts thereof. 
       
     
     
         2 . The compound of  claim 1 , wherein the compound is compound (12) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         3 . The compound of  claim 1 , wherein the compound is compound (13) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         4 . The compound of  claim 1 , wherein the compound is compound (14) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         5 . The compound of  claim 1 , wherein the compound is compound (15) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         6 . The compound of  claim 1 , wherein the compound is compound (16) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         7 . The compound of  claim 1 , wherein the compound is compound (17) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         8 . The compound of  claim 1 , wherein the compound is compound (18) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         9 . The compound of  claim 1 , wherein the compound is compound (19) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         10 . The compound of  claim 1 , wherein the compound is compound (20) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         11 . The compound of  claim 1 , wherein the compound is compound (21) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         12 . The compound of  claim 1 , wherein the compound is compound (22) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         13 . The compound of  claim 1 , wherein the compound is compound (23) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         14 . The compound of  claim 1 , wherein the compound is compound (24) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         15 . The compound of  claim 1 , wherein the compound is compound (25) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         16 . The compound of  claim 1 , wherein the compound is compound (26) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         17 . The compound of  claim 1 , wherein the compound is compound (27) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         18 . The compound of  claim 1 , wherein the compound is compound (28) 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         19 . A method of producing an expanded population of hematopoietic stem cells ex vivo, comprising contacting a population of hematopoietic stem cells with the compound of  claim 1 . 
     
     
         20 . A method of treating a disorder in a subject in need thereof comprising administering to the subject a pharmaceutically effective amount of the expanded population of hematopoietic stem cells being prepared by the method of  claim 19 .