title: Synthesis and anticonvulsant activities of some triazolothiadiazole derivatives.
abstract: The present study describes the synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (4a-4x) and their partially dehydrogenated products 5,6-dihydro-6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (5a-5n). The bioevaluation demonstrated that most compounds in the series of 4a-4x exhibited potent anticonvulsant activity in the maximal electroshock test. Among which, 6-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4h) emerged as the most promising candidate on the basis of its favorable ED(50) value of 23.7 mg/kg and PI value of 10.8. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4h displayed broad-spectrum activity in several models, and it may exert its anticonvulsant activity through affecting the GABAergic system.
authors.affiliation: College of Pharmacy, Yanbian University, Yanji, Jilin, China.
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Zheng-Qi
authors.initials: ZQ
authors.lastname: Dong
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Song
authors.forename: Bing
authors.initials: B
authors.lastname: Shu
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; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D013830:Thiadiazoles / 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; D003292:Convulsants; D013830:Thiadiazoles; D014230:Triazoles