Use of aminoglycoside analogs in the treatment of rett syndrome

Abstract

Compounds, methods and uses of pseudo-trisaccharide aminoglycosides represented by the general formula I: or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of alkyl, cycloalkyl and aryl; and all other variables and features are as described in the specification, in the treatment of Rett syndrome are disclosed.

1 . A method of treating Rett syndrome in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound represented by formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
       
       wherein:
 R 1  is selected from the group consisting of alkyl, cycloalkyl and aryl; 
 R 2  is hydrogen or (S)-4-amino-2-hydroxybutyryl (AHB); 
 R 3  is selected from the group consisting of hydrogen, alkyl, cycloalkyl and aryl; 
 a stereo-configuration of position 5″ is an R configuration or an S configuration; and 
 a stereo-configuration of position 6′, when chiral, is an R configuration or an S configuration. 
 
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein R 1  is alkyl. 
     
     
         6 . The method of  claim 5 , wherein said alkyl is methyl. 
     
     
         7 . The method of  claim 1 , wherein R 2  and R 3  are each hydrogen. 
     
     
         8 . The method of  claim 1 , wherein R 2  is AHB and R 3  is hydrogen. 
     
     
         9 . The method of  claim 1 , wherein R 2  is hydrogen and R 3  is alkyl. 
     
     
         10 . The method of  claim 1 , wherein R 2  is AHB and R 3  is alkyl. 
     
     
         11 . The method of  claim 10 , wherein said alkyl is methyl. 
     
     
         12 . The method of  claim 1 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 1 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         15 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 1 , wherein said Rett syndrome is associated with a MECP2 premature stop codon mutation. 
     
     
         18 . The method of  claim 17 , wherein said mutation is a nonsense mutation. 
     
     
         19 . The method of  claim 18 , wherein said MECP2 nonsense mutation is selected from the group consisting of R168X, R255X, R270X and R294X.