title: Synthesis and anticonvulsant activity evaluation of 5-phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-amines.
abstract: In the present study we describe the syntheses and anticonvulsant activity evaluation of 5-phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-amine derivatives. Their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock seizure test (MES) and the rotarod test, respectively. The majority of the compounds prepared were effective in the MES screens at a dose level of 100 mg/kg. Of these compounds, the most promising was compound 8h, which showed an ED(50) value of 27.4 mg/kg and a protective index (PI) value of 5.8. These values were superior to those provided by valproate (ED(50) and PI values of 272 and 1.6, respectively) in the MES test in mice. As well as its anti-MES efficacy, the potencies of compound 8h against seizures induced by pentylenetetrazole and thiosemicarbazide were also established, with the results suggesting that the GABAergic system-mediated mechanisms might be involved in its anticonvulsant activity.
authors.affiliation: College of Pharmacy, Yanbian University, Yanji City, Jilin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Ming
authors.initials: M
authors.lastname: Bian
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Shi-Ben
authors.initials: SB
authors.lastname: Wang
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000588:Amines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; 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; D011799:Quinazolines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045442:Rotarod Performance Test; D012640:Seizures / Q000188:drug therapy; D014230:Triazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000588:Amines; D000927:Anticonvulsants; D011799:Quinazolines; D014230:Triazoles