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

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 ED50 of 25.49 μmol/kg, TD50 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 (r2 = 0.9220, q2 = 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.

Graphical abstractSynthesis of series of aminobenzothiazole derivatives and their anticonvulsant activity with statistically reliable PHASE 3D-QSAR model (r2 = 0.9220, q2 = 0.8144) are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide