Phosphate esters of noribogaine

Abstract

Disclosed herein are phosphate esters of noribogaine and dihydronoribogaine, and esters and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and the methods of their use, including in the treatment of addiction and/or pain.

1 - 8 . (canceled) 
     
     
         9 . A compound of Formula I-A: 
       
         
           
           
               
               
           
         
         or a salt thereof wherein:
    refers to a single or a double bond provided that when   is a single bond, Formula I-A refers to the corresponding vicinal dihydro compound; 
 R 10  is hydrogen; R 11  is: 
 
       
       
         
           
           
               
               
           
         
       
       and
 n is 1 or 2; or R 10  is: 
 
       
         
           
           
               
               
           
         
         m is 0, 1, or 2; R 11  is hydrogen or: 
       
       
         
           
           
               
               
           
         
       
       and
 n is 0, 1, or 2;
 each R 2  is independently hydrogen, C 1 -C 12  alkyl, C 3 -C 10  cycloalkyl, C 6 -C 14  aryl, heteroaryl of 1 to 10 carbon atoms and 1 to 4 optionally oxidized heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; 
 R 21  is C 3 -C 10  cycloalkyl, C 6 -C 14  aryl, heteroaryl of 1 to 10 carbon atoms and 1 to 4 optionally oxidized heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. 
 
 
     
     
         10 . The compound of  claim 9  wherein R 10  is: 
       
         
           
           
               
               
           
         
         where m is 0. 
       
     
     
         11 . The compound of  claim 9  where R 11  is hydrogen. 
     
     
         12 . The compound of  claim 9  where R 10  is: 
       
         
           
           
               
               
           
         
         where m is 0 and R 11  is hydrogen. 
       
     
     
         13 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 9  and at least a pharmaceutically acceptable excipient. 
     
     
         14 . A method for treating pain in a patient which method comprises administering to said patient a therapeutically effective amount of the compound of  claim 9 . 
     
     
         15 . A method for treating pain in a patient which method comprises administering to said patient a therapeutically effective amount of the composition of  claim 13 .