Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective

A series of N-(substituted benzothiazol-2-yl)amide derivatives 2a-h and 4a-h were synthesized by the EDC coupling reactions of substituted-benzothiazol-2-amine with 4-oxo-4-phenylbutanoic acid/2-benzoyl benzoic acid and evaluated for their anticonvulsant and neuroprotective effect. N-(6-methoxybenzothiazol-2-yl)-4-oxo-4-phenylbutanamide (2f) emerged as the most effective anticonvulsant with median doses of 40.96 mg/kg (MES ED50), 85.16 mg/kg (scFTZ ED50) and 347.6 mg/kg (TD50). Furthermore, compound 2f displayed promising neuroprotective effect by lowering the levels of MDA and LDH; therefore, it represents a potential lead in search for safer and effective anticonvulsants having neuroprotective effects. (C) 2012 Elsevier Masson SAS. All rights reserved.