Synthesis and pharmacological evaluation of new 2-substituted-5-{2-[(2- halobenzyl)thiophenyl}-1,3,4-oxadiazoles as anticonvulsant agents

Abstract

A new series of 2-substituted-5-{2-[(2-halobenzyl)thio)phenyl}-1,3,4- xadiazoles was designed, synthesized and investigated for anticonvulsant activities. The designed compounds contain the main essential pharmacophore for binding to the benzodiazepine receptors. Conformational analysis and superimposition of energy minima conformers of designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main characteristics of the proposed benzodiazepine pharmacophore were well matched. Electroshock and pentylenetetrazole-induced lethal convulsion tests showed that some of the synthesized compounds had significant anticonvulsant activity. The structure-activity relationship study of these compounds indicated that the introduction of an amino group at position 2 of 1,3,4-oxadiazole ring and a fluoro substituent at the ortho position of the benzylthio moiety had the best anticonvulsant activity. Anticonvulsant effects of active compounds were antagonized by flumazenil, a benzodiazepine antagonist, which establishes the involvement of benzodiazepine receptors in these effects. © Österreichische Apotheker-Verlagsgesellschaft m. b. H.