Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac myosin

…, I Suehiro, A Tomasi, SC Valdez, W Wang…

文献索引：Morgan, Bradley P.; Muci, Alexander; Lu, Pu-Ping; Qian, Xiangping; Tochimoto, Todd; Smith, Whitney W.; Garard, Marc; Kraynack, Erica; Collibee, Scott; Suehiro, Ion; Tomasi, Adam; Valdez, S. Corey; Wang, Wenyue; Jiang, Hong; Hartman, James; Rodriguez, Hector M.; Kawas, Raja; Sylvester, Sheila; Elias, Kathleen A.; Godinez, Guillermo; Lee, Kenneth; Anderson, Robert; Sueoka, Sandra; Xu, Donghong; Wang, Zhengping; Djordjevic, Nebojsa; Malik, Fady I.; Morgans, David J. ACS Medicinal Chemistry Letters, 2010 , vol. 1, # 9 p. 472 - 477

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被引用次数: 39

摘要

We report the design, synthesis, and optimization of the first, selective activators of cardiac myosin. Starting with a poorly soluble, nitro-aromatic hit compound (1), potent, selective, and soluble myosin activators were designed culminating in the discovery of omecamtiv mecarbil (24). Compound 24 is currently in clinical trials for the treatment of systolic heart failure.