ACS Medicinal Chemistry Letters p. 472 - 477 (2010)
Update date:2022-08-04
Topics:
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.
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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