title: Design, synthesis, and anticonvulsant activity evaluation of 4-(3-alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones.
abstract: A series of 4-(3-alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones were synthesized using the appropriate synthetic route and evaluated experimentally in the maximal electroshock test; their neurotoxicities were evaluated by the rotarod neurotoxicity test. The structures of these compounds were confirmed by IR, MS, (1) H-NMR, and elementary analysis. All target compounds exhibited anticonvulsant activity to varying degrees in the maximal electroshock test. 4-(3-Benzyloxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one (4i) was the most promising compound with an ED(50) value of 30.5 mg/kg and a protective index (PI) of 18.63, showing a higher safety than the standard carbamazepine (PI=6.45). In addition, the potency of compound 4i against seizures induced by pentylenetetrazole and 3-mercaptopropionic acid suggested its broad-spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might be involved in its anticonvulsant activity.
authors.affiliation: College of Pharmacy, Yanbian University, Jilin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Shi-Ben
authors.initials: SB
authors.lastname: Wang
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004597:Electroshock; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D020258:Neurotoxicity Syndromes / Q000209:etiology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology; D014230:Triazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D014230:Triazoles