title: Design, synthesis and potential 6 Hz psychomotor seizure test activity of some novel 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302025, Rajasthan, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Birendra
authors.initials: B
authors.lastname: Shrivastava
authors.forename: Surendra N
authors.initials: SN
authors.lastname: Pandeya
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
mesh_terms: D000465:Algorithms; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D015195:Drug Design; D017029:Epilepsy, Complex Partial / Q000188:drug therapy*; D005823:Genetics; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009420:Nervous System / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D008024:Ligands; D011799:Quinazolines