Carbamate compounds for use in preventing or treating neuropathic pain and cluster and migraine headache-associated pain

Abstract

This invention is directed to a method for preventing or treating neuropathic pain and cluster and migraine headache-associated pain comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I): wherein phenyl is substituted at X with one to five halogen atoms independently selected from the group consisting of fluorine, chlorine, bromine and iodine; and; R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of hydrogen and C 1 -C 4 alkyl; wherein C 1 -C 4 alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, amino, nitro and cyano).

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         3 . A method for the prophylaxis of or treating migraine with or without aura comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I):  
       
         
           
           
               
               
           
         
       
       wherein 
 phenyl is substituted at X with one to five halogen atoms independently selected from the group consisting of fluorine, chlorine, bromine and iodine; and,  
 R 1 , R 2 , R 3  and R4 are independently selected from the group consisting of hydrogen and C 1 -C 4  alkyl; wherein C 1 -C 4  alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, amino, nitro and cyano).  
 
     
     
         4 . The method of  claim 3  wherein X is chlorine.  
     
     
         5 . The method of  claim 3  wherein X is substituted at the ortho position of the phenyl ring.  
     
     
         6 . The method of  claim 3  wherein R 1 , R 2 , R 3  and R 4  are selected from hydrogen.  
     
     
         7 . The method of  claim 3  wherein the compound of Formula (I) is selected from the group consisting of a racemic mixture of a compound of Formula (I), an enantiomer of a compound of Formula (I) and an enantiomeric mixture wherein an enantiomer of a compound of Formula (I) predominates.  
     
     
         8 . The method of  claim 7  wherein an enantiomer of Formula (I) predominates to the extent of about 90% or greater.  
     
     
         9 . The method of  claim 7  wherein an enantiomer of Formula (I) predominates to the extent of about 98% or greater.  
     
     
         10 . The method of  claim 3  wherein the compound of Formula (I) is a compound of Formula (Ia):  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2 , R 3  and R 4  are independently selected from the group consisting of hydrogen and C 1 -C 4  alkyl; wherein C 1 -C 4  alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, amino, nitro and cyano).  
 
     
     
         11 . The method of  claim 10  wherein R 1 , R 2 , R 3  and R 4  are selected from hydrogen.  
     
     
         12 . The method of  claim 10  wherein the compound of Formula (Ia) is selected from the group consisting of a racemic mixture of a compound of Formula (Ia), an enantiomer of a compound of Formula (Ia) and an enantiomeric mixture wherein an enantiomer of a compound of Formula (Ia) predominates.  
     
     
         13 . The method of  claim 12  wherein an enantiomer of Formula (Ia) predominates to the extent of about 90% or greater.  
     
     
         14 . The method of  claim 12  wherein an enantiomer of Formula (Ia) predominates to the extent of about 98% or greater.  
     
     
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         32 . The method of  claim 3  wherein the compound of Formula (I) is a compound of Formula (Ib):  
       
         
           
           
               
               
           
         
       
     
     
         33 . The method of  claim 32  wherein the compound of Formula (Ib) is selected from the group consisting of a racemic mixture of the compound of Formula (Ib), an enantiomer of the compound of Formula (Ib) and an enantiomeric mixture wherein an enantiomer of the compound of Formula (Ib) predominates.  
     
     
         34 . The method of  claim 3  wherein an enantiomer of Formula (Ib) predominates to the extent of about 90% or greater.  
     
     
         35 . The method of  claim 3  wherein an enantiomer of Formula (Ib) predominates to the extent of about 98% or greater.  
     
     
         36 . The method of  claim 3  wherein the compound of Formula (I) is an enantiomer of Formula (Ic) or an enantiomeric mixture wherein the enantiomer of Formula (Ic) predominates:  
       
         
           
           
               
               
           
         
       
     
     
         37 . The method of  claim 36  wherein the enantiomer of Formula (Ic) predominates to the extent of about 90% or greater.  
     
     
         38 . The method of  claim 36  wherein the enantiomer of Formula (Ic) predominates to the extent of about 98% or greater.  
     
     
         39 . The method of  claim 3  wherein the method is a method for slowing or delaying the progression of migraine with or without aura comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I).  
     
     
         40 . The method of claims  3 ,  7 ,  10 ,  32 ,  36  or  39  wherein the therapeutically effective amount is from about 0.01 mg/Kg/dose to about 100 mg/Kg/dose.