Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors: Design, synthesis and pharmacological evaluation

A new series of 4-chloro-N-(2-(substitutedphenyl)-4-oxothiazolidin-3-yl)-2-phenoxybenzamide derivatives were designed, synthesized and biologically evaluated as anticonvulsant agents. The designed compounds have the main essential functional groups for binding to the benzodiazepine receptors and 4-thiazolidinone ring as an anticonvulsant pharmacophore. Some of the new synthesized compounds showed considerable anticonvulsant activity in electroshock and pentylenetetrazole-induced lethal convulsion tests. Compound 5i, 4-chloro-N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-phenoxybenzamide, with the best activity was selected for evaluation of other benzodiazepine pharmacological effects. This compound induced significant sedative-hypnotic activity. However, it does not impair the learning and memory in the experimental condition. Flumazenil was able to antagonize the sedative-hypnotic and anticonvulsant effects of compound 5i indicating that benzodiazepine receptors are highly involved in the pharmacological properties of the novel compounds.