Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor
ACS Medicinal Chemistry Letters2010Vol. 1(2), pp. 64–69
Citations Over TimeTop 10% of 2010 papers
Ashok Arasappan, Frank Bennett, Stéphane Bogen, Srikanth Venkatraman, Melissa L. Blackman, Kevin X. Chen, Siska Hendrata, Yuhua Huang, Regina Huelgas, Latha G. Nair, Angela I. Padilla, Weidong Pan, R. E. PIKE, Patrick Pinto, Sumei Ruan, Mousumi Sannigrahi, Francisco Velázquez, Bancha Vibulbhan, Wanli Wu, Weiying Yang, Anil K. Saksena, Viyyoor Girijavallabhan, Neng‐Yang Shih, Jianshe Kong, Tao Meng, Yan Jin, J.K.Y. Wong, Paul E. McNamara, Andrew Prongay, Vincent Madison, John J. Piwinski, Kuo-Chi Cheng, Richard A. Morrison, Bruce A. Malcolm, Xiao Tong, Robert Ralston, F. George Njoroge
Abstract
Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (∼10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.
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