Compounds and methods for treating autism spectrum disorders

Abstract

The present invention relates to a compound of the following formula (I): or a pharmaceutically acceptable salt thereof, for use in the prevention or treatment of autism spectrum disorders (ASD).

1 . A method for the prevention or treatment of autism spectrum disorders (ASD) in an individual, comprising administering the individual a prophylactically or therapeutically active amount of at least one compound of the following formula (I): 
     
       
         
         
             
             
         
       
     
     in which:
 n represents 1 or 2, 
 A 1 , A 2  and A 3 , identical or different, represent a hydrogen atom, a halogen atom, or a linear or branched alkyl group having from 1 to 4 carbon atoms, 
 R 1 , R 2  and R 3 , identical or different represent a hydrogen atom or a linear or branched alkyl group having from 1 to 4 carbon atoms, and 
 Y represents —OH, ═O or —SH; 
 
     or a pharmaceutically acceptable salt thereof. 
   
   
       2 . The method of  claim 1 , wherein the compound of formula (I) is represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     in which n, A 1 , A 2 , A 3  and R 1  are as defined in  claim 1 . 
   
   
       3 . The method of  claim 1 , wherein the compound of formula (I) is represented by the following formula (III): 
     
       
         
         
             
             
         
       
     
   
   
       4 . The method of  claim 1 , wherein the ASD is autism. 
   
   
       5 . The method of  claim 1 , wherein the ASD is associated to a mutation of at least one GABA receptor subunit. 
   
   
       6 . The method of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is administered at a unit dose of from 100 mg to 1000 mg. 
   
   
       7 . The method of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is administered with a dosage regimen of from 10 mg/kg/d to 200 mg/kg/d. 
   
   
       8 . The method of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is in a form suitable for administration by the oral route. 
   
   
       9 . The method of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is in the form of sachets, tablets or capsules. 
   
   
       10 . The method of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is administered in combination with at least one additional compound intended for preventing or treating ASD. 
   
   
       11 . The method of  claim 10 , wherein the at least one additional compound intended for preventing or treating ASD is selected from the group constituted of serotonine, buspirone, clomipramine, fenfluramine, fluoxetine, fluvoxamine, sertraline, dopamine, haloperidol, L-dopa, pimozide, epinephrine, norepinephrine, beta-blockers, clonidine, desipramine, opiate antagonists, ACTH, clozapine, risperidone, vitamins B6 and B12 and melatonin. 
   
   
       12 . A pharmaceutical composition comprising as active substances,
 at least one compound of formula (I):   
     
       
         
         
             
             
         
       
     
     in which:
 n represents 1 or 2, 
 A 1 , A 2  and A 3 , identical or different, represent a hydrogen atom, a halogen atom, or a linear or branched alkyl group having from 1 to 4 carbon atoms, 
 R 1 , R 2  and R 3 , identical or different represent a hydrogen atom or a linear or branched alkyl group having from 1 to 4 carbon atoms, and 
 Y represents —OH, ═O or —SH; 
 
     or a pharmaceutically acceptable salt thereof, and
 at least one additional compound intended for preventing or treating ASD, optionally in association with a pharmaceutically acceptable vehicle. 
 
   
   
       13 . The pharmaceutical composition of  claim 12 , wherein the compound of formula (I) is represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     in which n, A 1 , A 2 , A 3  and R 1  are as defined in  claim 12 . 
   
   
       14 . The pharmaceutical composition of  claim 12 , wherein the compound of formula (I) is represented by the following formula (III): 
     
       
         
         
             
             
         
       
     
   
   
       15 . The pharmaceutical composition according to  claim 12 , wherein the wherein the at least one additional compound intended for preventing or treating ASD is selected from the group constituted of serotonine, buspirone, clomipramine, fenfluramine, fluoxetine, fluvoxamine, sertraline, dopamine, haloperidol, L-dopa, pimozide, epinephrine, norepinephrine, beta-blockers, clonidine, desipramine, opiate antagonists, ACTH, clozapine, risperidone, vitamins B6 and B12 and melatonin.