Synthesis and positive inotropic evaluation of N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides bearing piperazine and 1,4-diazepane moieties

被引：9

作者：

Wu, Yan ^{[2
]}

Ma, Long-Xu ^{[2
]}

Niu, Tian-Wei ^{[2
]}

Cui, Xun ^{[1
]}

Piao, Hu-Ri ^{[2
]}

机构：

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

[2] Yanbian Univ, Coll Pharm, Affiliated Minist Educ, Key Lab Nat Resources & Funct Mol Changbai Mt, Yanji 133000, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 13期

基金：

美国国家科学基金会;

关键词：

1,2,4]Triazolo[4,3-a]quinolin-1(2H)-one; Positive inotropic activity; Stroke volume; HEART; MORTALITY; DIGOXIN;

D O I：

10.1016/j.bmcl.2012.05.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two series of N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides bearing piperazine and 1,4-diazepane moieties were synthesized and screened for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Most of the derivatives exhibited better in vitro positive inotropic activity than the existing drug, milrinone, among which 2-(4-(4-chlorobenzyl)-1,4-diazepan-1-yl)-N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4] triazolo[4,3-a]quinolin-7-yl) acetamide 6c proved to be the most potent with 15.48 +/- 0.27% increased stroke volume (milrinone: 2.46 +/- 0.07%) at a concentration of 3 x 10 (5) M. The chronotropic effects of the compounds that exhibited inotropic effects were also evaluated. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4229 / 4232

页数：4

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