Synthesis and anticonvulsant activity of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

被引：38

作者：

Cui, LJ

Xie, ZF

Piao, HR

Li, G

Chai, KY

Quan, ZS ^{[1
]}

机构：

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

[2] Wonkwang Univ, Dept Chem, Iksan 570749, South Korea

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2005年 / 28卷 / 07期

关键词：

1,2,4]triazolo[4,3-a]quinoline; anticonvulsant; maximal electroshock test; pentylenetetrazole; neurotoxicity;

D O I：

10.1248/bpb.28.1216

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Starting from 6-hydroxy-3,4-dihydro-1H-quinoline-2-one, a series of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines was synthesized and their structures were characterized using IR, H-1-NMR, MS, and elemental analysis techniques. Anticonvulsant activity was evaluated in the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scMet) test, and rotarod neurotoxicity test. The most active compound was 7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline 4a. Its ED50 in the MES and scMet tests was 17.3 and 24 mg(.)kg(-1), respectively. The safest compound was 4g, 1-phenyl-7-benzyloxy-4,7-dihydro-[1,2,4]triazolo[4,3a]quinoline, with TD50 and protective index (PI) (PI=TD50/ED50) values of greater than 300mg(.)kg(-1) and 13, respectively. The PI value of compound 4g was better than that of most marketed drugs. Structure-activity relationships are also described in this paper.

引用

页码：1216 / 1220

页数：5

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