title: Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents.
abstract: A series of new 8-alkylamino-5, 6-dihydro-4H-benzo[f][1,2,4]triazolo [4,3-a]azepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. The results of these tests showed that 8-heptylamino-5,6- dihydro-4H-benzo[f][1,2,4] triazolo[4,3-a]azepine (7g) was the most promising compound, with median effective dose (ED50) of 19.0 mg/kg, and protective index (PI) value of 14.8 in the MES test, which is much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin (PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The possible structure-activity relationship was discussed.
authors.forename: Hui-Fan
authors.initials: HF
authors.lastname: Wu
authors.forename: Rong-Bi
authors.initials: RB
authors.lastname: Han
authors.forename: Chun-Zi
authors.initials: CZ
authors.lastname: Jin
authors.affiliation: College of Science, Yanbian University, Yanji City, Jilin Province 133000, China. fypiao@ybu.edu.cn.
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Piao
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D001381:Azepines; D003292:Convulsants; D010433:Pentylenetetrazole