title: Design and synthesis of 10-alkoxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4]oxazepine derivatives with anticonvulsant activity.
abstract: A series of novel 10-alkoxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4]oxazepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). In the MES test, compound 10-Heptyloxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4]oxazepine (8f) was found to possess better anticonvulsant activity and higher safety than marketed drugs carbamazepine and phenytoin with an ED(50) value of 6.9 mg/kg a PI value of 9.5. To explain the possible mechanism of anticonvulsant activity, compound 8f was tested in pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid and Bicuculline induced seizures tests. The results suggest that compound 8f exerts anticonvulsant activity through GABA-mediated mechanism.
authors.affiliation: College of Pharmacy, Yanbian University, No. 1829, JuZi Street, Yanji, Jilin 133000, China.
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Wei
authors.forename: Fu-Nan
authors.initials: FN
authors.lastname: Li
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Sun
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002490:Central Nervous System / Q000187:drug effects; D015195:Drug Design; D051379:Mice; D010077:Oxazepines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D010100:Oxygen / Q000737:chemistry; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013057:Spectrum Analysis
chemical_list: D000927:Anticonvulsants; D010077:Oxazepines; D010100:Oxygen