Synthesis and Biological Evaluation of [1,2,4]Triazolo[3,4-a]phthalazine and Tetrazolo[5,1-a]phthalazine Derivatives Bearing Substituted Benzylpiperazine Moieties as Positive Inotropic Agents

Authors

  • Yan Wu,

    1. Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China
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  • Liang-Peng Sun,

    1. Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China
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  • Long-Xu Ma,

    1. Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China
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  • Jian Che,

    1. Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China
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  • Ming-Xia Song,

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

    Corresponding author
    1. Yanbian University College of Medicine, Yanji, China
    • Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China
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  • Hu-Ri Piao

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

Abstract

Two series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)tetrazolo[5,1-a]phthalazine. 8 m in particular was identified as the most potent with an increased stroke volume of 12.02 ± 0.20% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10–5 m. The chronotropic effects of the compounds that exhibited good potency were also evaluated.

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