title: Synthesis and Anticonvulsant Activity Evaluation of 3-alkoxy-4-(4-(hexyloxy/heptyloxy)phenyl)-4H-1,2,4 -triazole.
abstract: A series of 3-alkoxy-4-(4-(hexyloxy/heptyloxy) phenyl)-4H-1,2,4-triazole was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, compound 3-heptyloxy-4-(4-(hexyloxy) phenyl)-4H-1,2,4-triazole (5f) was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED50) of 37.3 mg/Kg, median toxicity dose (TD50) of 422.5 mg/Kg, and the protective index (PI) of 11.3 which is much greater than the reference drug carbamazepine with PI value of 6.4. As well as demonstrating the anti-MES efficacy of compound 5f, its potency against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also established, with the results suggesting that GABA-mediated mechanisms might be involved in its anticonvulsant activity, such as enhancing of GABAergic neurotransmission or activity, activate GAD or inhibit GABA-T, and GABAA-mediated mechanisms.
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China. ; Department of Pharmacy ， Chongqing Three Gorges Medical College , No.366, Tianxing Road, Baian Ba, Wanzhou, Chonqing, 404120, China.
authors.forename: Ying-Quan
authors.initials: YQ
authors.lastname: Fang
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China.
authors.forename: Da-Chuan
authors.initials: DC
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China.
authors.forename: Shi-Ben
authors.initials: SB
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China.
authors.forename: Zhe-San
authors.initials: ZS
authors.lastname: Quan
keywords: 3-Mercaptopropionic acid; Anticonvulsant activity; Bicuculline; Neurotoxicity; Pentylenetetrazole; Synthesis; Triazole; Triazolone