Compounds useful for treating neurological disorders

Abstract

The invention relates to the use of compounds for the preparation of a medicament for treating neuropathic pain, migraine, psychiatric disorder and/or neuronal degeneration. The invention additionally relates to a pharmaceutical composition comprising compounds for treating neuropathic pain, migraine, psychiatric disorder and/or neuronal degeneration. A method for treating neuropathic pain, migraine, psychiatric disorder and/or neuronal degeneration is also provided.

1 . A method for treating a disease or condition selected from: neuropathic pain, migraine, and neuronal degeneration, in a mammal comprising administering to the mammal, a therapeutically effective amount of a compound of formula [A]:  
       
         
           
           
               
               
           
         
         as racemic mixtures or as individual stereoisomers or mixtures of racemic and stereoisomers,  
         wherein  
         (i) X is selected from OH and NR 1 R 2 ;  
         (ii) R 1 , R 2  are independently selected from H and C 1 -C 6  alkyl;  
         (iii) n is 0 or 1; and  
         (iv) (a) R 3 , R 4  are independently selected from H and C 1 -C 6  alkyl; R 5,  R 6  are independently selected from H and C 1 -C 6  alkyl; or 
 (b) one of R 3  and R 4,  together with one of R 5  and R 6 , form a cyclopropyl ring, and the other of R 3 , R 4 , R 5  and R 6  is selected from H and C 1 -C 6  alkyl,  
 including pharmaceutically acceptable salts, hydrates and solvates of the compound of formula [A], with the exclusion of the following compounds in racemic and stereoisomeric forms for treating migraine: propylisopropyl acetic acid, propylisopropyl acetamide, valnoctamide, valnoctic acid, diisopropyl acetamide and diisopropyl acetic acid.  
 
       
     
     
         2 . A method for treating a psychiatric disorder in a mammal comprising administering to the mammal, a therapeutically effective amount of a compound of formula [A] as defined in  claim 1 , with the exclusion of compounds of formula II:  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently selected from H and C 1 -C 6  alkyl.  
       
     
     
         3 . A method according to  claim 1  for treating a disease or condition selected from: neuropathic pain, migraine, and neuronal degeneration, in a mammal comprising administering to said mammal, a therapeutically effective amount of a compound of formula I  
       
         
           
           
               
               
           
         
         as racemic mixtures or as individual stereoisomers or mixtures of racemic and stereoisomers,  
         wherein  
         (i) X is selected from OH and NR 1 R 2 ;  
         (ii) R 1 , R 2  are independently selected from H and C 1 -C 6  alkyl; and  
         (iii) (a) R 3 , R 4  are independently selected from H and C 1 -C 6  alkyl; R 5 , R 6  are independently selected from H and C 1 -C 6  alkyl; or 
 (b) one of R 3  and R 4 , together with one of R 5  and R 6 , form a cyclopropyl ring, and the other of R 3 , R 4 , R 5  and R 6  is selected from H and C 1 -C 6  alkyl,  
 including pharmaceutically acceptable salts, hydrates and solvates of the compound of formula [I], with the exclusion of the following compounds in racemic and stereoisomeric forms for treating migraine: valnoctamide, valnoctic acid, diisopropyl acetamide and diisopropyl acetic acid.  
 
       
     
     
         4 . The method according to  claim 1  wherein said C 1 ,-C 6  alkyl group is a straight or a branched alkyl group.  
     
     
         5 . The method according to  claim 3  wherein the total number of carbon atoms of R 3 , R 4 , R 5  and R 6  in a compound of formula I is two.  
     
     
         6 . The method according to  claim 3  wherein 
 (i) X is selected from OH and NR 1 R 2 ;    (ii) R 1 , R 2  are independently selected from H and C 1 -C 6  alkyl; and    (iii) (a) R 3 , R 4  are independently selected from H, methyl and ethyl; R 5 , R 6  are independently selected from H, methyl and ethyl; or 
 (b) one of R 3  and R 4 , together with one of R 5  and R 6 , form a cyclopropyl ring, and the other of R 3 , R 4 , R 5  and R 6  is selected from H, methyl and ethyl.  
   
     
     
         7 . The method according to  claim 3  wherein 
 X is selected from OH and NR 1 R 2 ; R 1 , R 2  are independently selected from H and C 1 -C 6  alkyl; and one of R 3  and R 4 , together with one of R 5  and R 6 , form a cyclopropyl ring and the other of R 3 , R 4 , R 5  and R 6  is a methyl.    
     
     
         8 . The method according to  claim 7  having the structural formula II  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently selected from H and C 1 -C 6  alkyl.  
       
     
     
         9 . The method according to  claim 7  wherein at least one of R 1  and R 2  is H and the other of R 1  and R 2  is a C 1 -C 6  alkyl.  
     
     
         10 . The method according to  claim 7  wherein said C 1 -C 6  alkyl is a methyl.  
     
     
         11 . The method according to  claim 7  wherein said compound is N-Methyl-2,2,3,3 -tetramethylcyclopropanecarboxamide.  
     
     
         12 . The method according to  claim 7  wherein said compound is 2,2,3,3-tetramethylcyclopropanecarboxamide.  
     
     
         13 . The method according to  claim 3  wherein said compound is 2-ethyl-3-methyl-pentanoic acid amide, as racemic mixture or as individual stereoisomers or mixtures of racemic and stereoisomers, including pharmaceutically acceptable salts, hydrates and solvates thereof, for the treatment of neuropathic pain and neuronal degeneration.  
     
     
         14 . The method according to  claim 3  wherein said compound is 2-ethyl-3-methyl-pentanoic acid, as racemic mixture or as individual stereoisomers or mixtures of racemic and stereoisomers, including pharmaceutically acceptable salts, hydrates and solvates thereof, for the treatment of neuropathic pain and neuronal degeneration.  
     
     
         15 . The method according to  claim 7  wherein said compound is 2,2,3,3-tetramethylcyclopropanecarboxylic acid.  
     
     
         16 . The method according to  claim 1  for treating neuropathic pain or neuronal degeneration, wherein said compound is propyl isopropylacetamide (PID) as racemic mixture or as individual 2R and 2S stereoisomers or mixtures of racemic and stereoisomers, including pharmaceutically acceptable salts, hydrates and solvates thereof.  
     
     
         17 . The method according to  claim 1  wherein said compound is diisopropylacetamide (DID).  
     
     
         18 . The method according to  claim 1  wherein said compound is diisopropylacetic acid (DIA).  
     
     
         19 . The method according to  claim 1  wherein said disease or condition is a neuropathic pain.  
     
     
         20 . The method according to  claim 1  wherein the route of administration of said compound is selected from oral, parenteral, topical, transdermal, mucosal, rectal and buccal administration.  
     
     
         21 . The method according to  claim 1  wherein the route of administration of said compound is selected from oral and parenteral administration.  
     
     
         22 . The method according to  claim 21  wherein said parenteral route of administration is selected from intravenous, intramuscular, intraperitoneal and subcutaneous administration.  
     
     
         23 . The method of  claim 1  wherein said mammal is a human.