Anticonvulsant and anxiolytic methods of using receptor subtype selective agents

Abstract

Methods of using orally active benzodiazepine derivatives and their salts are disclosed. These compounds and their salts have anticonvulsant and anxiolytic activity with reduced sedative, hypnotic, muscle relaxant, or ataxic effects.

1 . A method for the treatment and/or prevention of convulsions comprising:
 administering to a mammalian subject in need of such treatment an effective amount of a compound of formula VIII, or a salt thereof,   
     
       
         
         
             
             
         
       
       wherein X is N or CH; Y and Z are taken together with the two intervening carbon atoms to form a ring selected from phenyl and thienyl, which ring is substituted at the C(8) position with at least the substituent —C≡C—R, where R is H, Si(CH 3 ) 3 , t-butyl, isopropyl, methyl, or cyclopropyl; R 1  is H, CH 3 , CF 3 , CH 2 CH 3 , CH 2 CF 3 , or cyclopropyl; R 2  is a substituted or unsubstituted at least partially unsaturated 5 or 6 membered cyclic or heterocyclic ring, wherein if substituted, the substituent is F, Cl, Br, or NO 2  at the 2′-position. 
     
   
   
       2 . The method according to  claim 1 , wherein the compound is 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       wherein R is H or Si(CH 3 ) 3 , R′ is H or CH 3 , and X′ is H, F, Cl, Br, or NO 2 . 
     
   
   
       3 . The method according to  claim 1 , wherein the compound is 
     
       
         
         
             
             
         
       
     
   
   
       4 . A method for the treatment and/or prevention of anxiety comprising:
 administering to a mammalian subject in need of such treatment an effective amount of a compound of formula VIII, or a salt thereof,   
     
       
         
         
             
             
         
       
       wherein: X is N or CH; Y and Z are taken together with the two intervening carbon atoms to form a ring selected from phenyl and thienyl, which ring is substituted at the C(8) position with at least the substituent —C≡C—R, where R is H, Si(CH 3 ) 3 , t-butyl, isopropyl, methyl, or cyclopropyl; R 1  is H, CH 3 , CF 3 , CH 2 CH 3 , CH 2 CF 3 , or cyclopropyl; R 2  is a substituted or unsubstituted at least partially unsaturated 5 or 6 membered cyclic or heterocyclic ring, wherein if substituted, the substituent is F, Cl, Br, or NO 2  at the 2′-position. 
     
   
   
       5 . The method according to  claim 4 , wherein the compound is 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       wherein R is H or Si(CH 3 ) 3 , R′ is H or CH 3 , and X′ is H, F, Cl, Br, or NO 2 . 
     
   
   
       6 . The method according to  claim 4 , wherein the compound is