Synthesis and Positive Inotropic Activity of [1,2,4]Triazolo[4,3-a] Quinoxaline Derivatives Bearing Substituted Benzylpiperazine and Benzoylpiperazine Moieties

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-02, Vol.22 (2), p.273-273
• Main Authors: Liu, Xue-Kun, Ma, Long-Xu, Wei, Zhi-Yu, Cui, Xun, Zhan, Shi, Yin, Xiu-Mei, Piao, Hu-Ri
• Format: Article
• Language: English
• Subjects: [1,2,4]triazolo[4,3-a] quinoxaline; Adenosine; Animals; atrium; Cardiotonic Agents - chemical synthesis; Cardiotonic Agents - pharmacology; Dose-Response Relationship, Drug; Heart Atria - drug effects; Heart failure; Heart Failure - drug therapy; Heart Failure - etiology; Heart Failure - physiopathology; Hydrocarbons; Laboratories; milrinone; Milrinone - pharmacology; Molecular Structure; Myocardial Contraction - drug effects; Piperazines - chemistry; positive inotropic activity; Potash; Quinoxaline; Quinoxalines - chemical synthesis; Quinoxalines - pharmacology; Rabbits; Stroke; Stroke volume; Stroke Volume - drug effects
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22020273

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3- ] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.