title: Design and synthesis of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives with anticonvulsant activity.
abstract: A series of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives were synthesized using 4-hydroxyquinolin-2(1H)-one as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and their neurotoxicities were measured by the rotarod test. The results of these tests demonstrated that 5-hexyloxy-[1,2,4]triazolo[4,3-a]quinoline (3f) was the most potent anticonvulsant, with median effective dose (ED(50)) of 19.0mg/kg and protective index (PI=TD(50)/ED(50)) values of 5.8 in the MES test. Compound 5-benzyloxy-[1,2,4]triazolo[4,3-a]quinoline (3j), exhibited a little weaker activity than compound 3f in controlling the seizure induced by MES test at the dose of 22.8 mg/kg, but it possessed lower neurotoxicity with PI value of 12.0, which was safer than marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, compound 3j was tested in pentylenetetrazole test, isoniazid test, thiosemicarbazide test, 3-mercaptopropionic acid and strychnine test.
authors.affiliation: Key Laboratory of Organism Functional Factors of the Changbai Mountain, Yanbian University, Ministry of Education, Yanji, Jilin 133002, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Guo
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Wei
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Jia
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhao
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan