Compounds and compositions for treating chemical warfare agent-induced injuries

Abstract

Compounds and compositions for treating injuries caused by exposure to chemical warfare agents are described herein.

1 - 11 . (canceled) 
     
     
         12 . A method of treating an injury to the skin or respiratory tract resulting from exposure to a chemical warfare agent, the method comprising administering to a subject an effective amount of a compound of Formula (IV), or a salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein, 
       each of R 1  and R 2  is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl, each of which is optionally substituted with 1-4 R 5 ;
 L is NR 6 SO 2 , SO 2 NR 6 , OC(O)NR 6 , NR 6 C(O)O, NR 6 C(O)NR 6 , NR 6 C(O), C(O)NR 6 , O, C(O), S, S(O), S(O) 2 , NR 6 , CH 2 , cyclyl, aryl, heterocyclyl, or heteroaryl; 
 R 3  is cyclyl, heterocyclyl, aryl, heteroaryl, each of which is optionally substituted with 1-4 R 7 ; 
 
       each R 5  is independently halo, hydroxyl, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, amido, alkylamido, dialkylamido, thioyl, sulfonyl, cyclyl, heterocyclyl, aryl, or heteroaryl; 
       each R 6  is independently H, C 1 -C 6  alkyl, arylalkyl, S(O)alkyl, acetyl, amidyl, or S(O)H; 
       each R 7  is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halo, hydroxyl, alkoxy, aryloxy, arylalkoxy, amino, akylamino, dialkylamino, thioyl, alkylthioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea, hydroxyl alkoxyl, alkoxy alkoxyl, acyl, nitro, cyano, each of which is independently substituted with 1-3 R8; 
       each R 8  is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl, halo, hydroxyl, alkoxy, aryloxy, amino, akylamino, dialkylamino, thioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea acyl, nitro, cyano, cyclyl, heterocyclyl, aryl, or heteroaryl; 
       each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; 
       each R 9  is independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl, halo, hydroxyl, alkoxy, aryloxy, arylalkoxy, amino, akylamino, dialkylamino, thioyl, alkylthioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea, acyl, nitro, cyano, each of which is independently substituted with 1-3 R 8 . 
     
     
         13 . The method of  claim 12 , wherein R 1  and R 2  are independently C 1 -C 6  alkyl. 
     
     
         14 . The method of  claim 12 , wherein L is C(O)NR 6  and m is 1. 
     
     
         15 . The method of  claim 12 , wherein R 3  is heteroaryl, substituted with 1-4 R 7 . 
     
     
         16 . The method of  claim 12 , wherein R 7  is aryl optionally substituted by 1-3 R 8 . 
     
     
         17 . The method of  claim 12 , wherein n is 0. 
     
     
         18 . The method of  claim 12 , wherein the compound is a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 12 , wherein the compound is administered orally, via intramuscular injection, or topically. 
     
     
         20 . The method of  claim 12 , wherein the chemical warfare agent is tear gas. 
     
     
         21 . The method of  claim 12 , wherein the chemical warfare agent is chlorine. 
     
     
         22 . The method of  claim 12 , wherein the chemical warfare agent is mustard gas. 
     
     
         23 . The method of  claim 12 , wherein the subject is a human. 
     
     
         24 . A method of treating an injury to the skin or respiratory tract resulting from exposure to a chemical warfare agent, the method comprising administering to a subject an effective amount of a compound of Formula (VI), or a salt thereof 
       
         
           
           
               
               
           
         
       
       wherein,
 R 1  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl, each of which is optionally substituted with 1-4 R 5 ; 
 R 2  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or cycyl, each of which is optionally substituted with 1-4 R 5 ; 
 L is NR 6 SO 2 , SO 2 NR 6 , OC(O)NR 6 , NR 6 C(O)O, NR 6 C(O)NR 6 , NR 6 C(O), C(O)NR 6 , O, C(O), S, S(O), S(O) 2 , NR 6 , CH 2 , cyclyl, aryl, heterocyclyl, or heteroaryl; 
 R 3  is cyclyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with 1-4 R 7 ; 
 
       each R 5  is independently halo, hydroxyl, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, amido, alkylamido, dialkylamido, thioyl, sulfonyl, cyclyl, heterocyclyl, aryl, or heteroaryl; 
       each R 6  is independently H, C 1 -C 6  alkyl, arylalkyl, S(O)alkyl, acetyl, amidyl, or S(O)H; 
       each R 7  is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halo, hydroxyl, alkoxy, aryloxy, arylalkoxy, amino, akylamino, dialkylamino, thioyl, alkylthioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea, hydroxyl alkoxyl, alkoxy alkoxyl, acyl, nitro, cyano, each of which is independently substituted with 1-3 R 8 ; 
       each R 8  is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl, halo, hydroxyl, alkoxy, aryloxy, amino, akylamino, dialkylamino, thioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea acyl, nitro, cyano, cyclyl, heterocyclyl, aryl, or heteroaryl; 
       each R 9  is independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl, halo, hydroxyl, alkoxy, aryloxy, arylalkoxy, amino, akylamino, dialkylamino, thioyl, alkylthioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea, acyl, nitro, cyano, each of which is independently substituted with 1-3 R 8 ; 
       each m and n are independently 0, 1, 2, 3, 4, 5, or 6. 
     
     
         25 . The method of  claim 24 , wherein R 1  and R 2  are independently C 1 -C 6  alkyl. 
     
     
         26 . The method of  claim 24 , wherein L is C(O)NR 6  and m is 1. 
     
     
         27 . The method of  claim 24 , wherein R 3  is heteroaryl, substituted with 1-4 R 7 . 
     
     
         28 . The method of  claim 24 , wherein R 7  is aryl optionally substituted by 1-3 R 8 . 
     
     
         29 . The method of  claim 24 , wherein n is 0. 
     
     
         30 . The method of  claim 24 , wherein the compound is a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         31 . The method of  claim 24 , wherein the compound is administered orally, via intramuscular injection, or topically. 
     
     
         32 . The method of  claim 24 , wherein the chemical warfare agent is tear gas. 
     
     
         33 . The method of  claim 24 , wherein the chemical warfare agent is chlorine. 
     
     
         34 . The method of  claim 24 , wherein the chemical warfare agent is mustard gas. 
     
     
         35 . The method of  claim 24 , wherein the subject is a human.