No abstract

A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emesis and useful in the treatment of seizure disorders for which phenytoin is presently indicated.

A selected group of alkoxy- and halogen-substituted 5-benzylidino- and 5-benzylhydantoins was prepared and screened for anticonvulsant activity as measured by the ability of the compound to prevent maximal electroshock and metrazol-induced threshold clonic seizures in rats. The structure-activity studies revealed 5-[3-(trifluoromethyl)benzyl]hydantoin (14) to be the most potent member of the series.

Several 9-alkyl-6-substituted-purines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. Most compounds were prepared in three steps from 5-amino-4,6-dichloropyrimidine or in two steps via alkylation of 6-chloropurine. Potent anticonvulsant activity against MES resided in compounds that contain a benzyl substituent at the 9-position of 6-(methylamino)- or 6-(dimethyl-amino)purine. Among commonly used agents for control of seizures, this type of structure represents a new class of potent anticonvulsant agents.

No abstract