title: Synthesis and Pharmacological Evaluation of New 3,4-Dihydroisoquinolin Derivatives Containing Heterocycle as Potential Anticonvulsant Agents.
abstract: Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4a-tand9a-e) were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and pentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, ¹H-NMR,13C-NMR, and mass spectral data. Among them, 9-(exyloxy)-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3(2H)-one (9a) showed significant anticonvulsant activity in MES tests with an ED50value of 63.31 mg/kg and it showed wide margins of safety with protective index (PI > 7.9). It showed much higher anticonvulsant activity than that of valproate. It also demonstrated potent activity against PTZ-induced seizures. A docking study of compound9ain the benzodiazepine (BZD)-binding site of γ-aminobutyric acidA(GABAA) receptor confirmed possible binding of compound9awith the BZD receptors.
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. zhjzhishixiang@163.com.
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. 2016001065@ybu.edu.cn.
authors.forename: Qing-Kun
authors.initials: QK
authors.lastname: Shen
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. cmjin@ybu.edu.cn.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Jin
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. zsquan@ybu.edu.cn.
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D003975:Diazepam / Q000378:metabolism; D004195:Disease Models, Animal; D004597:Electroshock; D004949:Estazolam / Q000378:metabolism; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010433:Pentylenetetrazole / Q000633:toxicity; D066244:Proton Magnetic Resonance Spectroscopy; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: C000617872:9-(hexyloxy)-5,6-dihydro-(1,2,4)triazolo(3,4-a)isoquinolin-3(2H)-one; D000927:Anticonvulsants; C109852:G 1616; D007546:Isoquinolines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D014230:Triazoles; D004949:Estazolam; D014635:Valproic Acid; D003975:Diazepam; D010433:Pentylenetetrazole
keywords: MES; anticonvulsant; isoquinoline; molecular docking; synthesis