Radiomitigating pharmaceutical formulations

Abstract

The present disclosure relates to compounds of Formula (I) and (II), compositions containing the compounds (alone or in combination with other agents), and their use to prevent, mitigate or treat a) damage induced by ionizing radiation, b) inflammation or c) cancer.

1 . A compound having the structure of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 A 5  is a secondary or tertiary amino substituent, and 
 A 6  is a substituted or unsubstituted aryl or heteroaryl group. 
 
     
     
         2 . A compound of  claim 1 , wherein the aryl or heteroaryl group bears at least one substituent including a nitro substitutent. 
     
     
         3 . The compound of  claim 2 , wherein the nitro substituent is disposed at a position on A 6  distal to the sulfonyl. 
     
     
         4 . The compound of  claim 1 , wherein A 5  is a heterocyclic amine. cm  5 . The compound of  claim 1 , wherein A 5  is NR 15 R 16 , wherein each of R 15  and R 16 , independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, provided that R 15  and R 16  are not both H. 
     
     
         6 . A compound of  claim 1 , having the structure of Formula II: 
       
         
           
           
               
               
           
         
         wherein: 
         X is N or —C(H)—, and 
         Y 1  and Y 2  are each independently lower alkyl or Y 1  and Y 2  taken together with X form a heterocyclyl ring. 
       
     
     
         7 . The compound of  claim 6 , wherein Y 1  and Y 2  are each ethyl. 
     
     
         8 . The compound of  claim 6 , wherein Y 1  and Y 2  taken together with X form a piperazine ring. 
     
     
         9 . The compound of  claim 6 , wherein Y 1  and Y 2  taken together with X form: 
       
         
           
           
               
               
           
         
         wherein 
         X is N; 
         G is selected from N or —C(H)—; 
         Z is absent or selected from substituted or unsubstituted alkyl, heteroalkyl, alkenyl, or alkynyl; 
         R 4  is absent or selected from substituted or unsubstituted aryl and heteroaryl; and 
         R 5  and R 6  are each independently absent or lower alkyl. 
       
     
     
         10 . The compound of  claim 9 , wherein G is N and R 4  is selected from phenyl, 4-fluorophenyl and 3-chlorophenyl. 
     
     
         11 . The compound of  claim 9 , wherein Z is absent. 
     
     
         12 . The compound of  claim 9 , wherein Z is prop-2-en-1-yl and R 4  is phenyl. 
     
     
         13 . The compound of  claim 6 , wherein Y 1  and Y 2  taken together with X form: 
       
         
           
           
               
               
           
         
         wherein X is —C(H)—, and 
         R 4  is absent or selected from substituted or unsubstituted aryl and heteroaryl. 
       
     
     
         14 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable excipient or solvent. 
     
     
         15 . A method of mitigating an effect of ionizing radiation on a cell, organ, tissue, or organism, comprising contacting the cell, organ, tissue, or organism with a compound of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein the compound contacts the cell before, during, or after exposure to ionizing radiation. 
     
     
         17 . A method of treating inflammation in an organism, comprising administering to the organism a compound of  claim 1 . 
     
     
         18 . A method of treating cancer in an organism, comprising administering to the organism a compound of  claim 1 . 
     
     
         19 . The method of  claim 18 , wherein the organism is a mammal. 
     
     
         20 . The compound of  claim 3 , wherein A 6  is optionally substituted 4-nitrophenyl.