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

Bradley P. Morgan,Alexander Muci,Pu-Ping Lu,Xiangping Qian,Todd Tochimoto,Whitney W. Smith,Marc Garard,Erica Kraynack,Scott Collibee,Ion Suehiro,Adam Tomasi,S. Corey Valdez,Wenyue Wang,Hong Jiang,James Hartman,Hector M. Rodriguez,Raja Kawas,Sheila Sylvester,Kathleen A. Elias,Guillermo Godinez,Kenneth Lee,Robert Anderson,Sandra Sueoka,Donghong Xu,Zhengping Wang,Nebojsa Djordjevic,Fady I. Malik,David J. Morgans

ACS medicinal chemistry letters（2010）

Cited 96|Views11
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Abstract
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.
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Key words
omecamtiv mecarbil,cardiac myosin,small molecule enzyme activator,systolic heart failure,biomedical research,bioinformatics
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