title: Synthesis and evaluation of the anticonvulsant activity of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives.
abstract: Two series of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives (6a-q and 7a-q) were synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. All of the compounds prepared were effective in the MES screens. Among which, compound 7j was considered as the most promising one with an ED50 value of 26.3 mg/kg and a superior protective index value of 12.6. The potency of compound 7j against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid and bicuculline suggested that two different mechanisms of action might potentially be involved in its anticonvulsant activity, including the inhibition of voltage-gated ion channels and the modulation of GABAergic activity. A computational study was also conducted to predict the pharmacokinetic properties of the compounds prepared, with the results supporting the use of these compounds as a group of promising antiepileptic agents.
authors.affiliation: College of Pharmacy, Yanbian University , Yanji, Jilin , China and.
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Song
authors.forename: Shi-Ben
authors.initials: SB
authors.lastname: Wang
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D019295:Computational Biology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D051379:Mice; D015394:Molecular Structure; D045442:Rotarod Performance Test; D012640:Seizures / Q000188:drug therapy; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D013841:Thiazepines; D014230:Triazoles