Design, synthesis and potential 6 Hz psychomotor seizure test activity of some novel 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one

Thirty new 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The most active compound of the series was 3-({(E)-[3-(4-chloro-3-methylphenoxy)phenyl]methylidene}amino)-2-phenylquinazolin-4(3H)-one PhQZ 7, which showed 100% protection (4/4, 0.5 h) and 75% protection (3/4, 0.25 h) at a dose of 100 mg/kg in mice. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in Lamarckian genetic algorithm based flexible docking studies.

Thirty 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one were designed, synthesized and evaluated for anticonvulsant activity and neurotoxicity. Computational study involving distance mapping, log P calculation, prediction of pharmacokinetic properties and docking study were reported.Figure optionsDownload as PowerPoint slideResearch highlights
► Thirty novel 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one were designed, synthesized and reported as potential anticonvulsants.
► 3-({(E)-[3-(4-chloro-3-methylphenoxy)phenyl]methylidene}amino)-2-phenyl quinazolin-4(3H)-one PhQZ 7 was most active compound of the series and showed an ED50 and a TD50 of >350 mg/kg at a time of peak effect (TPE) of 0.5 h in quantitative 6 Hz and toxicity test.
► 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one exhibited good binding properties with glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in Lamarckian genetic algorithm based flexible docking studies.