Four series of [1,2,4]triazolo[3,4-]phthalazine and tetrazolo[5,1-]phthalazine derivatives bearing substituted piperazine moieties were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume in isolated rabbit-heart preparations. Several compounds were developed and showed favorable activities compared to the standard drug milrinone, with (4-([1,2,4]triazolo[3,4-]phthalazin-6-yl)piperazin-1-yl)(-tolyl)methanone () being identified as the most potent with an increased stroke volume of 19.15±0.22% (milrinone: 2.46±0.07%) at a concentration of 3×10M. A preliminary study of mechanism of action revealed that displayed its positive inotropic effect may be related to the PDE-cAMP-PKA signaling pathway. Compounds exhibiting inotropic effects were also evaluated in terms of the chronotropic effects.

中文翻译：

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带有取代哌嗪部分的[1,2,4]三唑并[3,4-a]酞嗪和四唑并[5,1-a]酞嗪衍生物的合成和正性肌力评价

合成了四个系列的带有取代哌嗪部分的[1,2,4]三唑并[3,4-]酞嗪和四唑并[5,1-]酞嗪衍生物，并通过测量分离的左心房搏出量来评估其正性肌力活性。兔心制剂。与标准药物米力农相比，开发了几种化合物，并显示出良好的活性，其中（4-（[1,2,4]三唑并[3,4-]酞嗪-6-基）哌嗪-1-基）（-甲苯基）甲酮 () 被认为是最有效的，浓度为 3×10M 时每搏输出量增加 19.15±0.22%（米力农：2.46±0.07%）。作用机制初步研究表明其正性肌力作用可能与PDE-cAMP-PKA信号通路有关。还根据变时作用评价表现出正性肌力作用的化合物。