Radio-protective and chemo-protective substituted thiols

Abstract

The present disclosure relates to prodrugs, double prodrugs, derivatives and analogues of 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol. The compounds of this disclosure also relate to formula I: The use of these compounds as radio- and chemo-protectors is also described.

1 .- 29 . (canceled) 
     
     
         30 . A compound according to formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, 
         wherein:
 each R 0  is independently H; 
 A is H; and 
 B is a (6- to 8-membered)heterocycloalkyl containing two N atoms or Moiety B 2 , wherein the (6- to 8-membered)heterocycloalkyl containing two N atoms is substituted with a cyclopropyl, a cyclobutyl, a cyclopentyl, or a cyclohexyl so as to form a bicyclic ring; and 
 wherein Moiety B 2  has the structure: 
 
       
       
         
           
           
               
               
           
         
         wherein n is an integer selected from the group consisting of 1, 2, 3, and 4. 
       
     
     
         31 . The compound according to  claim 30 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein B is a heterocycle selected from: 
       
         
           
           
               
               
           
         
       
       wherein the heterocycle is substituted with a cyclopropyl, a cyclobutyl, a cyclopentyl, or a cyclohexyl so as to form a bicyclic ring. 
     
     
         32 . A pharmaceutical composition comprising the compound according to  claim 30 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier. 
     
     
         33 . The pharmaceutical composition according to  claim 32 , wherein the pharmaceutical composition is formulated for oral administration. 
     
     
         34 . The pharmaceutical composition according to  claim 32 , wherein the pharmaceutical composition is formulated for parenteral administration. 
     
     
         35 . The pharmaceutical composition according to  claim 34 , wherein the parenteral administration is subcutaneous, intravenous, intramuscular, or intrathecal. 
     
     
         36 . The pharmaceutical composition according to  claim 32 , wherein the pharmaceutical composition further comprises an antioxidant. 
     
     
         37 . A compound according to formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, 
         wherein:
 each R 0  is independently H; 
 A is H; and 
 B is a (6- to 8-membered)heterocycloalkyl containing two N atoms, wherein the (6- to 8-membered)heterocycloalkyl is substituted with a cyclobutyl so as to form a bicyclic ring. 
 
       
     
     
         38 . A pharmaceutical composition comprising the compound according to  claim 37 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         39 . The pharmaceutical composition according to  claim 38 , wherein the pharmaceutical composition is formulated for oral administration. 
     
     
         40 . The pharmaceutical composition according to  claim 38 , wherein the pharmaceutical composition is formulated for parenteral administration. 
     
     
         41 . The pharmaceutical composition according to  claim 40 , wherein the parenteral administration is subcutaneous, intravenous, intramuscular, or intrathecal. 
     
     
         42 . The pharmaceutical composition according to  claim 38 , wherein the pharmaceutical composition further comprises an antioxidant. 
     
     
         43 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         44 . A pharmaceutical composition comprising the compound according to  claim 43 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         45 . The pharmaceutical composition according to  claim 44 , wherein the pharmaceutical composition is formulated for oral administration. 
     
     
         46 . The pharmaceutical composition according to  claim 44 , wherein the pharmaceutical composition is formulated for parenteral administration. 
     
     
         47 . The pharmaceutical composition according to  claim 46 , wherein the parenteral administration is subcutaneous, intravenous, intramuscular, or intrathecal. 
     
     
         48 . The pharmaceutical composition according to  claim 44 , wherein the pharmaceutical composition further comprises an antioxidant.