Targeted nitroxide agents

Abstract

Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

1 - 23 . (canceled) 
     
     
         24 . A compound having the structure 
       
         
           
           
               
               
           
         
         wherein X is one of 
       
       
         
           
           
               
               
           
         
       
       and R is hydrogen, C 1 -C 6  straight or branched-chain alkyl, or a C 1 -C 6  straight or branched-chain alkyl further comprising a phenyl (C 6 H 5 ) group, that is unsubstituted or is methyl-, hydroxyl- or fluoro-substituted; R 4  is hydrogen, C 1 -C 6  straight or branched-chain alkyl, or a C 1 -C 6  straight or branched-chain alkyl further comprising a phenyl (C 6 H 5 ) group, that is unsubstituted or is methyl-, hydroxyl- or fluoro-substituted; R 3  is —NH—R 5 , —O—R 5  or CH 2 -R 5 , and R 5  is an —N—O., —N—OH or N═O containing group; and R is —C(O)—R 6 , —C(O)O—R 6 , or —P(O)—(R 6 ) 2 , wherein R 6  is C 1 -C 6  straight or branched-chain alkyl or C 1 -C 6  straight or branched-chain alkyl further comprising one or more phenyl (—C 6 H 5 ) groups that are independently unsubstituted, or methyl-, ethyl-, hydroxyl- or fluoro-substituted. 
     
     
         25 . The compound of  claim 24  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         26 . The compound of  claim 24  having the structure 
       
         
           
           
               
               
           
         
       
       wherein R 4  is hydrogen or methyl. 
     
     
         27 - 39 . (canceled) 
     
     
         40 . The compound of  claim 24 , wherein R 5  has the structure 
       
         
           
           
               
               
           
         
       
     
     
         41 . The compound of  claim 24 , wherein R is Ac, Boc, Cbz, or —(O)-Ph 2 . 
     
     
         42 . The compound of  claim 24 , in which R 1 , R 4  and R 6  are independently chosen from hydrogen, methyl, ethyl, propyl, 2-propyl, butyl, t-butyl, pentyl, hexyl, benzyl, and hydroxybenzyl. 
     
     
         43 . The compound of  claim 24  wherein X is 
       
         
           
           
               
               
           
         
       
     
     
         44 . The compound of  claim 24 , wherein X is 
       
         
           
           
               
               
           
         
       
     
     
         45 . The compound of  claim 24 , wherein R 5  has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         46 . The compound of  claim 25 , wherein R 5  has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         47 . The compound of  claim 26 , wherein R 5  has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         48 . The compound of  claim 42 , wherein R 5  has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         49 . A compound of structure: 
       
         
           
           
               
               
           
         
       
     
     
         50 . A compound of structure: