Synthesis and anticonvulsant activity of 7-phenyl-6,7-dihydro-[1,2,4] triazolo[1,5-a]pyrimidin-5(4H)-ones and their derivatives

被引：39

作者：

Deng, Xian-Qing ^{[1
]}

Quan, Li-Na ^{[1
]}

Song, Ming-Xia ^{[1
]}

Wei, Cheng-Xi ^{[2
]}

Quan, Zhe-Shan ^{[1
]}

机构：

[1] Yanbian Univ, Coll Pharm, Yanji 133002, Jilin, Peoples R China

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

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 07期

基金：

中国国家自然科学基金;

关键词：

Synthesis; Anticonvulsant; Triazolo[1,5-a]pyrimidin; Imidazo[1,2-a]pyrimidin; Pyrazolo[1,5-a]pyrimidin; Maximal electroshock; ANTIEPILEPTIC DRUGS; EPILEPSY; GABA; ANTAGONISM; SEIZURES; DESIGN;

D O I：

10.1016/j.ejmech.2011.04.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein, we described the syntheses and anticonvulsant activities of 7-(substituted-phenyl)-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones (1a-1o) and their derivatives. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock test (MES). The most promising compound 1i showed significant anticonvulsant activity in MES test with ED(50) value of 19.7 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drugs. In addition, the potence of compound 1i against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide, 3-Mercaptopropionic acid, and Bicuculline in the chemical-induced seizure tests suggested that compound 1i displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action including inhibiting voltage-gated ion channels and modulating GABAergic activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：2955 / 2963

页数：9

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