Compounds useful for treating injuries from warfare agents

Abstract

Compounds and compositions for treating disorders related to TRPA1 are described herein.

We claim: 
     
         1 - 10 . (canceled) 
     
     
         11 . A method of treating an injury to a subject in need thereof resulting from exposure to a chemical warfare agent, the method comprising administering to a subject an effective amount of a compound of Formula VII, or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein each of A, B, C, and D is CR 1  or N, provided that no more than 1 of A, B, C, and D is N; 
         each of X and Y is, independently, N—R, O or S, where R is H, alkyl, OH, OR′, CN, NO 2 , or SO 2 R′, and where R′ is H or C 1-6  alkyl; 
         each R 1  is, independently, H, optionally substituted C 1-6  alkyl, optionally substituted C 2-6  alkenyl, optionally substituted C 2-6  alkynyl, optionally substituted heterocyclyl, hydroxyl, optionally substituted C 1-6  alkoxy, optionally substituted C 1-6  alkenyloxy, cyano, halo, acyl, amino, optionally substituted alkylamino, aminoalkyl, amido, acylamino, alkylurea, alkylcarbamoyl, carboxyl, optionally substituted alkylcarboxyl, thioyl, optionally substituted alkylthio, SO 3 H, optionally substituted alkylsulfinyl, optionally substituted alkylsulfonyl, or nitro; 
         each of R 3  and R 4  is, independently, H, optionally substituted C 1-6  alkyl, arylalkyl, heteroarylalkyl, alkoxyalkyl, COR 10 , CO 2 R 10 , CH 2 CO 2 R 10 , or CONHR 10 , where R 10  is H or optionally substituted C 1-6  alkyl; and 
         R 6  is hydroxyl, C 1-6  alkenyloxy, cyano, acyl, amino, optionally substituted alkylamino, aminoalkyl, amido, acylamino, alkylurea, alkylcarbamoyl, carboxyl, optionally substituted alkylcarboxyl, thioyl, optionally substituted alkylthio, SO 3 H, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl. 
       
     
     
         12 . The method of  claim 11 , wherein each of A, B, C, and D is CR 1 . 
     
     
         13 . The method of  claim 11 , wherein each of A, B, C, and D is CR 1 , and R 1  is H. 
     
     
         14 . The method of  claim 11 , wherein at least one of A, B, C, and D is N. 
     
     
         15 . The method of  claim 11 , wherein D is N. 
     
     
         16 . The method of  claim 11 , wherein each of X and Y is, independently, O or S. 
     
     
         17 . The method of  claim 11 , wherein each of R 3  and R 4  is, independently, H, optionally substituted C 1-6  alkyl, arylalkyl, heteroarylalkyl, alkoxyalkyl, or COR 10 . 
     
     
         18 . The method of claim  1 , wherein R 6  is hydroxyl, C 1-6  alkenyloxy, cyano, acyl, amino, optionally substituted alkylamino, amido, acylamino, carboxyl, optionally substituted alkylcarboxyl. 
     
     
         19 . A method of treating an injury to a subject in need thereof resulting from exposure to a chemical warfare agent, the method comprising administering to a subject an effective amount of a compound of Formula V, or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein each of A, B, C, and D is CR 1  or N, provided that no more than 2 of A, B, C, and D are N; 
         each of X and Y is, independently, N—R, O or S, where R is H, alkyl, OH, OR′, CN, NO 2 , or SO 2 R′, where R′ is H or C 1-6  alkyl; 
         each R 1  is, independently, H, optionally substituted C 1-6  alkyl, optionally substituted C 2-6  alkenyl, optionally substituted C 2-6  alkynyl, optionally substituted heterocyclyl, hydroxyl, optionally substituted C 1-6  alkoxy, optionally substituted C 1-6  alkenyloxy, cyano, halo, acyl, amino, optionally substituted alkylamino, aminoalkyl, amido, acylamino, alkylurea, alkylcarbamoyl, carboxyl, optionally substituted alkylcarboxyl, thioyl, optionally substituted alkylthio, SO 3 H, optionally substituted alkylsulfinyl, optionally substituted alkylsulfonyl, or nitro; each of R 3  and R 4  is, independently, H, optionally substituted C 1-6  alkyl, arylalkyl, heteroarylalkyl, alkoxyalkyl, COR 10 , CO 2 R 10 , CH 2 CO 2 R 10 , or CONHR 10 , where R 10  is H or optionally substituted C 1-6  alkyl; and 
         R 5  is hydroxyl, optionally substituted C 1-6  alkoxy, optionally substituted C 1-6  alkenyloxy, alkyloxyalkoxy, cyano, acyl, amino, optionally substituted alkylamino, aminoalkyl, amido, acylamino, alkylurea, alkylcarbamoyl, carboxyl, optionally substituted alkylcarboxyl, thioyl, optionally substituted alkylthio, SO 3 H, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl. 
       
     
     
         20 . The method of  claim 19 , wherein each of A, B, C, and D is CR 1 . 
     
     
         21 . The method of  claim 19 , wherein each of A, B, C, and D is CR 1  and R1 is H. 
     
     
         22 . The method of  claim 19 , wherein at least one of A, B, C, and D is N. 
     
     
         23 . The method of  claim 19 , wherein D is N. 
     
     
         24 . The method of  claim 19 , wherein X is O and Y is S. 
     
     
         25 . The method of  claim 19 , wherein each of R 3  and R 4  is, independently, H, optionally substituted C 1-6  alkyl, arylalkyl, heteroarylalkyl, alkoxyalkyl, or COR 10 . 
     
     
         26 . The method of  claim 19 , wherein R 5  is hydroxyl, optionally substituted C 1-6  alkoxy, optionally substituted C 1-6  alkenyloxy, alkyloxyalkoxy, cyano, acyl, amino, optionally substituted alkylamino, aminoalkyl, amido, acylamino, carboxyl, or optionally substituted alkylcarboxyl. 
     
     
         27 . The method of any one of  claim 11  or  19 , wherein the subject is a human. 
     
     
         28 . The method of any one of  claim 11  or  19 , wherein the injury is inflammation, burn, itch, pain, rash, blisters, sweating, secretions from the mouth, nose, or lung, difficulty breathing, shortness of breath, coughing, phlegm production and narrowing of the airways.