title: Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: a hybrid pharmacophore approach.
abstract: Novel N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives were synthesized and evaluation of their anticonvulsant effects was done using various models of experimental epilepsy. Initial anticonvulsant activities of the compounds were investigated using intraperitoneal (i.p.) maximal electroshock shock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The quantitative assessment after oral administration in rats showed that the most active was 2-methyl-4-oxo-N-(6-(trifluoromethoxy)benzo[d]thiazol-2-ylcarbamoyl)quinazoline-3(4H)-carbothioamide (SA 24) with ED50 values of 82.5 μmol/kg (MES) and 510.5 μmol/kg (scPTZ). This molecule was more potent than phenytoin and ethosuximide which were used as reference antiepileptic drugs. To explain the possible mechanism for anticonvulsant action, some of the selected active compounds were subjected to GABA (γ-amino butyric acid) assay and AMPA ((S)-2-amino-3-(3-hydroxyl-5-methyl-4-isoxazolyl) propionic acid) induced seizure test.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy Jamia Hamdard, New Delhi 110062, India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Malik
authors.forename: Radhe Shyam
authors.initials: RS
authors.lastname: Bahare
authors.forename: Suroor Ahmad
authors.initials: SA
authors.lastname: Khan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D011799:Quinazolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013844:Thiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D013854:Thioamides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D000927:Anticonvulsants; C587472:N-(benzo(d)thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide; D011799:Quinazolines; D013844:Thiazoles; D013854:Thioamides; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
keywords: 4-Oxoquinazoline-3(4H)-carbothioamide; AMPA induced seizure; Anticonvulsant activity; Benzothiazole; DHANPQHXXULONF-UHFFFAOYSA-N; Neuroprotection; QABFTVHENPQHIO-UHFFFAOYSA-N