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(E)-2-(4-肉桂基哌嗪-1-基)-N-(1-取代-4,5-二氢-[1,2,4]三唑并[4,3-a]喹啉-7-基)乙酰胺的合成及正性肌力作用评价。

Synthesis and positive inotropic evaluation of (E)-2-(4-cinnamylpiperazin-1-yl)-N-(1-substituted-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides.

机构信息

Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, P. R. China.

出版信息

Arch Pharm (Weinheim). 2012 Dec;345(12):980-8. doi: 10.1002/ardp.201200159. Epub 2012 Sep 26.

Abstract

A series of (E)-2-(4-cinnamylpiperazin-1-yl)-N-(1-substituted-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume on isolated rabbit heart preparations. This class of compounds presented favorable in vitro activity compared with the standard drug, milrinone, among which N-(1-(3-chlorophenyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-cinnamylpiperazin-1-yl)acetamide 5e was found to be the most potent with 16.58 ± 0.11% increased stroke volume (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10(-5)  M. The chronotropic effects of the compounds having inotropic effects were also evaluated.

摘要

一系列(E)-2-(4-肉桂基哌嗪-1-基)-N-(1-取代-4,5-二氢-[1,2,4]三唑并[4,3-a]喹啉-7-基)乙酰胺被合成,并通过测量在分离的兔心制剂上的左心房冲程体积来评估其正性肌力活性。与标准药物米力农相比,这一类化合物表现出有利的体外活性,其中 N-(1-(3-氯苯基)-4,5-二氢-[1,2,4]三唑并[4,3-a]喹啉-7-基)-2-(4-肉桂基哌嗪-1-基)乙酰胺 5e 在 3×10(-5)M 的浓度下表现出最强的活性,增加冲程体积 16.58±0.11%(米力农:2.46±0.07%)。具有正性肌力作用的化合物的变时作用也得到了评估。

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