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In this work, a novel series of phthalimide-4,5-dihydrothiazole-amide derivatives  5a–f  have been synthesized and evaluated for their anti-epileptic activities against pentylenetetrazole (PTZ)-induced seizure in mice. Among the synthesized compounds, the most potent was 4-chloro derivative  5b  with zero mortality in PTZ test. Molecular docking was performed to investigate the modes of interactions between GABA A  receptor and synthetized compounds. Docking results were in good agreement with observed experimental data and indicate that among six new derivatives, compound  5b  with highest effective anticonvulsant properties, had lowest binding energy. This compound also exhibited better anti-epileptic activity and lower binding energy for connect to GABA A  receptor in comparison to thalidomide as standard anti-epileptic agent.

Synthesis and Evaluation of Anti-Epileptic Properties of New Phthalimide-4,5-Dihydrothiazole-Amide Derivatives