title: Synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-a](tetrazolo[5,1-a])phthalazine derivatives.
abstract: With the aim of finding new anticonvulsant drugs, new 6-substituted-[1,2,4]triazolo[3,4-a] (tetrazolo[5,1-a]) phthalazine derivatives (1-34) have been designed and synthesized. All the compounds were evaluated for their anticonvulsant activities using the maximal electroshock test (MES). Most of the synthesized compounds exhibited potent anticonvulsant activities in the MES. The most promising compound 14 showed significant anticonvulsant activity in MES test with ED₅₀ value of 9.3 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drug Carbamazepine. And the potency of compound 14 against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide and 3-Mercaptopropionic acid in the chemical-induced seizure tests suggested that compound 14 displayed wide spectrum of activity in several models.
authors.affiliation: College of Pharmacy, Yanbian University, Yanji City, Jilin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Bian
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Gong
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Wei
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D015097:3-Mercaptopropionic Acid; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D004597:Electroshock; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007538:Isoniazid; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010433:Pentylenetetrazole; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012663:Semicarbazides
chemical_list: C586211:6-(3-(trifluoromethyl)benzyloxy)(1,2,4)triazolo(3,4-a)phthalazine; D000927:Anticonvulsants; D006575:Heterocyclic Compounds, 3-Ring; D010793:Phthalazines; D012663:Semicarbazides; C005151:thiosemicarbazide; D015097:3-Mercaptopropionic Acid; D007538:Isoniazid; D010433:Pentylenetetrazole