Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin.
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ABSTRACT:
SUBMITTER: Morgan BP
PROVIDER: S-EPMC4007828 | biostudies-other | 2010 Dec
REPOSITORIES: biostudies-other
Publications
Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin.
Morgan Bradley P BP Muci Alexander A Lu Pu-Ping PP Qian Xiangping X Tochimoto Todd T Smith Whitney W WW Garard Marc M Kraynack Erica E Collibee Scott S Suehiro Ion I Tomasi Adam A Valdez S Corey SC Wang Wenyue W Jiang Hong H Hartman James J Rodriguez Hector M HM Kawas Raja R Sylvester Sheila S Elias Kathleen A KA Godinez Guillermo G Lee Kenneth K Anderson Robert R Sueoka Sandra S Xu Donghong D Wang Zhengping Z Djordjevic Nebojsa N Malik Fady I FI Morgans David J DJ
ACS medicinal chemistry letters 20100820 9
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. ...[more]
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