Treatment of epilepsy

Abstract

The present invention discloses isoquinolines and 1H-2-Benzopyranes and their use in the treatment and prevention in epilepsy and other seizures. The present invention further discloses methods to screen isoquinoline- and 1H-2-Benzopyran-like molecules as pharmaceutically active compounds.

1 . An isoquinoline or 1H-2-Benzopyran, selected from the group consisting of TMC-120A, TMC-120B, TMC-120C, penicisochroman G, ustusorane B, compound 6 (7-methylfuro[3,2-h]isoquinoline-3(2H)-one) and compound 7 (2-(7-methyl-2,3-dihydrofuro[3,2-h]isoquinoline-2-yl)-propan-2-ol) for use in the treatment or prevention of epilepsy. 
     
     
         2 . An isoquinoline or 1H-2-Benzopyran in accordance with  claim 1 , in combination with halimide or plinabulin, for use in the treatment or prevention of epilepsy. 
     
     
         3 . A method for identifying pharmaceutical compounds against epilepsy, the method comprising the steps of:
 providing a compound which comprises a benzene ring fused to a) a pyridine ring b) or a puran ring and fused to a modified or unmodified furan group as depicted in formula 1 or formula 2
 and, 
   
       
         
           
           
               
               
           
         
         
           
             testing the compound for antiseizure activity. 
           
         
       
     
     
         4 . The method according to  claim 3 , wherein said pyridine or puran ring is further methylated as depicted in formula 3 or formula 4 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method according to  claim 3 , wherein said compound comprises a moiety as depicted in formula 5 or 6 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method according to  claim 3 , which comprises an isoquinoline or 1H-2-Benzopyran moiety and testing the compound for antiseizure activity. 
     
     
         7 . The method according to  claim 3 , wherein the compound with a isoquinoline or 1H-2-Benzopyran moiety is a TMC-120A, TMC-120B, TMC-120C, penicisochroman G, ustusorane B, furo[3,2-h]isoquinoline-3(2H)-one,7-methyl- and furo[3,2-h]isoquinoline-2-methanol,2,3-dihydro-α,α,7-trimethyl-,(2S)—. 
     
     
         8 . The method according to  claim 3 , wherein halimide is added to said compound for testing antiseizure activity. 
     
     
         9 . The method according to  claim 3 , wherein the isoquinoline or 1H-2-Benzypuran is a compound as depicted in  FIGS. 1 and/or 2 , with modified molecular structure or stereochemistry. 
     
     
         10 . The method according to  claim 3 , wherein anti-seizure activity is determined in a zebrafish model. 
     
     
         11 . The method according to  claim 3 , wherein anti-seizure activity is further determined in a mammalian model. 
     
     
         12 . The method according to  claim 3 , further comprising the step of testing the compound for a side effect. 
     
     
         13 . The method according to  claim 3 , further comprising the step of formulating a compound with determined anti-seizure activity into a pharmaceutical composition with an acceptable carrier, for use in the treatment of epilepsy.