Design and synthesis of 10-alkoxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4] oxazepine derivatives with anticonvulsant activity

被引：57

作者：

Deng, Xian-Qing ^{[2
]}

Wei, Cheng-Xi ^{[1
,2
]}

Li, Fu-Nan ^{[2
]}

Sun, Zhi-Gang ^{[1
]}

Quan, Zhe-Shan ^{[2
]}

机构：

[1] Inner Mongolia Univ Nationalities, Inst Neurosurg, Tongliao 028007, Inner Mongolia, Peoples R China

[2] Yanbian Univ, Coll Pharm, Yanji 133000, Jilin, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 07期

基金：

中国国家自然科学基金;

关键词：

Synthesis; Triazole; Benzo[f][1,4]oxazepine; Anticonvulsant; Maximal electroshock; ANTIEPILEPTIC DRUGS; GABA; ANTAGONISM;

D O I：

10.1016/j.ejmech.2010.03.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 10-alkoxy-5, 6-dihydro-triazolo[4,3-d]enzo[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 ED50 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. (c) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：3080 / 3086

页数：7

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