Synthesis of new triazole acetamides with inotropic effects

• Published in: Bioorganic & medicinal chemistry letters 2013-02, Vol.23 (3), p.757-760
• Main Authors: Wu, Yan, Ma, Long-Xu, Sun, Liang-Peng, Song, Ming-Xia, Cui, Xun, Piao, Hu-Ri
• Format: Article
• Language: English
• Subjects: 3,4-Dihydro-2(1H)-quinolinone; acetamides; Acetamides - chemical synthesis; Acetamides - chemistry; Acetamides - pharmacology; Animals; Atrium; Cardiotonic Agents - chemical synthesis; Cardiotonic Agents - chemistry; Cardiotonic Agents - pharmacology; chemistry; Drugs; Heart - drug effects; Milrinone; Milrinone - pharmacology; Positive inotropic activity; Rabbits; Stroke; Stroke volume; Triazole acetamides; triazoles; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.11.078

A series of new triazole acetamides with inotropic effects were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume on isolated rabbit-heart preparations. A series of new triazole acetamides 5a–w were synthesized and evaluated for their positive inotropic activity of left atrium stroke volume on isolated rabbit-heart preparations. The majority of the derivatives presented favorable in vitro activity compared with the reference drug, milrinone. Among them triazole acetamide 5a was identified as the most potent with 20.29±0.18% increased stroke volume (milrinone: 2.46±0.07%) at a concentration of 3×10–5M. The chronotropic effects of the compounds having inotropic effects were also evaluated.