Synthesis of 2-(4-Substitutedbenzyl-[1,4]Diazepan-1-yl)-N-(1-Methyl-4,5-Dihydro-[1,2,4]Triazolo[4,3-A]Quinolin-7-Yl)Acetamides as Inotropic Agents

Authors

  • Bai-Jun Ye,

    1. Key Laboratory of Natural Resources of Changbai Mountains & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, China
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  • Xue-Kun Liu,

    1. Key Laboratory of Natural Resources of Changbai Mountains & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, China
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  • Sheng-Ming Jiang,

    1. Key Laboratory of Natural Resources of Changbai Mountains & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, China
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  • Xun Cui,

    Corresponding author
    1. Yanbian University College of Preclinical Medicine, Yanji 133000, China
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  • Hu-Ri Piao

    Corresponding author
    1. Key Laboratory of Natural Resources of Changbai Mountains & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, China
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Corresponding authors: Hu-Ri Piao,piaohuri@yahoo.com.cn; Xun Cui, cuixun@ybu.edu.cn

Abstract

In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)-[1,4]-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide (6m) was the most potent, increasing stroke volume by 8.38 ± 0.16% (milrinone 2.45 ± 0.06%) at 3 × 10−5 m. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.

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