New fluorinated quinazolinone derivatives as anticonvulsant agents

ObjectivesThe aim of the present work was to synthesize some novel fluorinated quinazolinones and to evaluate them for anticonvulsant activity and neurotoxicity.MethodsEight compounds were synthesized. Their anticonvulsant activity was evaluated from maximal electroshock-induced seizures in eight groups of six Swiss mice given the test compounds (100 mg/kg intraperitoneally), one control group given 10% DMSO (10 ml/kg) and one given the reference compound phenytoin (100 mg/kg). Neurotoxicity was evaluated by the rotarod test in eight groups of four Swiss mice given the test compounds (100 mg/kg), one given saline (10 ml/kg) and one given phenytoin (100 mg/kg). The structure–activity relations of the compounds and C log P correlations were determined to explain the results.ResultsFour compounds showed significant anticonvulsant activity with low neurotoxicity when compared with the reference drug.ConclusionThe newly designed compounds could be useful templates for the design and optimization of more active analogues as anticonvulsant agents with low neurotoxicity.