Enantiomers of spiro-oxindole compounds and their uses as therapeutic agents

Abstract

This invention is directed to the (S)-enantiomer of the compound of formula (I): or a pharmaceutically acceptable solvate or prodrug thereof. This (S)-enantiomer is useful for the treatment of diseases or conditions, such as pain, which are ameliorated or alleviated by the modulation of voltage-gated sodium channels.

What is claimed is: 
     
         1 . A method of treating a disease or a condition in a mammal selected from pruritis, multiple sclerosis, depression, cardiovascular diseases, respiratory diseases, psychiatric diseases, neurological diseases and seizures, and combinations thereof, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of the (S)-enantiomer of 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one having the following formula (I-S): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable solvate or prodrug thereof. 
       
     
     
         2 . The method of  claim 1  wherein the disease or condition is pruritus. 
     
     
         3 . A method of treating a disease or condition in a mammal by the inhibition of ion flux through a voltage-gated sodium channel in the mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of the (S)-enantiomer of 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one having the following formula (I-S): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable solvate or prodrug thereof. 
       
     
     
         4 . A method of decreasing ion flux through a voltage-gated sodium channel in a cell in a mammal, wherein the method comprises contacting the cell with the (S)-enantiomer of 1′-{[5-(trifluoromethyhfuran-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one having the following formula (I-S): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable solvate or prodrug thereof. 
       
     
     
         5 . A method for preparing the (S)-enantiomer of 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one having the following formula (I-S): 
       
         
           
           
               
               
           
         
         wherein the method comprises: 
         (a) treating a compound of the following formula: 
       
       
         
           
           
               
               
           
         
         
           with 2-bromomethyl-5-trifluoromethylfuran under suitable conditions to form a compound of formula (I): 
         
       
       
         
           
           
               
               
           
         
       
       and
 (b) isolating the (S)-enantiomer 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one from the compound of formula (I) by suitable chiral high pressure liquid chromatography conditions or by suitable simulated moving bed chromatography conditions.