Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole

Abstract

A series of 6-substituted-[3-substituted-prop-2-eneamido]benzothiazole 9– 32 and 6-substituted-2-[(1-acetyl-5-substituted)-2-pyrazolin-3-yl]aminobenzothiazole 33– 56 were synthesized using appropriate synthetic route and evaluated experimentally against maximal electroshock test. Selected compounds were evaluated for neurotoxicity, hepatotoxicity and behavioral study. The most active compound, 6-methyl-2-[(1-acetyl-5-(4-chlorophenyl))-2-pyrazolin-3-yl]aminobenzothiazole 52 exhibited an ED 50 of 25.49 μmol/kg, TD 50 of 123.87 μmol/kg and high protective index (PI) of 4.86 compared to standard drug phenytoin. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power ( r 2 = 0.9220, q 2 = 0.8144) was achieved. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may aids in the design of potent aminobenzothiazole derivatives as anticonvulsant agents.