Design, synthesis and pharmacological screening of potential anticonvulsant agents using hybrid approach

Abstract

A series of 9H, 10H, 3-[ N- 4 methyl -2-benzamido thiophen 3-yl carbonyl amino [2-(2′-phenyl 1′- ethylenyl)] 10-(aryl) thiazolidino [4, 5-b] 1, 5 benzodiazepine [ 7a– 7h] were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Anticonvulsant activity was determined after intra-peritoneal administration to mice by supramaximal electroshock seizures model and Isoniazide Hydrazone induced seizures model. Motor impairement was determined using actophotometer and rotarod apparatus. Among the synthesized compounds two [JG 7a and JG 7e] compounds exhibited significant anticonvulsant activity after intra-peritoneal administration. Active compounds carry hydroxy substitutent at 2-position and methoxy at 4-position in the phenyl ring at C 5 of benzodiazepine. In present we study conclude that small polar and electron rich groups contribute significantly for anticonvulsant activity while electronegative substitutents showed lesser contribution for anticonvulsant activity.