title: Synthesis and Anticonvulsant Activity Evaluation of 4-Phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one and Its Derivatives.
abstract: A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones (6a-x) with triazole and other heterocyclic substituents (7-14) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI6o  > 25.5, PI6q  > 26.0). Compounds 6o and 6q showed significant oral activity against MES-induced seizures in mice, with ED50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline.
authors.affiliation: College of Pharmacy, Yanbian University, Yanji, Jilin, China.
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Yanbian University, Yanji, Jilin, China.
authors.forename: Shi-Ben
authors.initials: SB
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Fu-Nan
authors.initials: FN
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Engineering Technology Research Center of Marine Biomedical Products, Food and Pharmacy College, Zhejiang Ocean University, Zhoushan, Zhejiang, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Guan
authors.affiliation: College of Pharmacy, Yanbian University, Yanji, Jilin, China.
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal; D001640:Bicuculline; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D052999:Quinazolinones; D014230:Triazoles; D010433:Pentylenetetrazole; D001640:Bicuculline
keywords: Anticonvulsant; BIC; Maximal electroshock; Synthesis; Triazole; sc-PTZ