2. Academic Validation
  3. Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

  • ACS Med Chem Lett. 2010 Feb 15;1(2):64-9. doi: 10.1021/ml9000276.
Ashok Arasappan 1,  Frank Bennett 1,  Stephane L Bogen 1,  Srikanth Venkatraman 1,  Melissa Blackman 1,  Kevin X Chen 1,  Siska Hendrata 1,  Yuhua Huang 1,  Regina M Huelgas 1,  Latha Nair 1,  Angela I Padilla 1,  Weidong Pan 1,  Russell Pike 1,  Patrick Pinto 1,  Sumei Ruan 1,  Mousumi Sannigrahi 1,  Francisco Velazquez 1,  Bancha Vibulbhan 1,  Wanli Wu 1,  Weiying Yang 1,  Anil K Saksena 1,  Viyyoor Girijavallabhan 1,  Neng-Yang Shih 1,  Jianshe Kong 1,  Tao Meng 1,  Yan Jin 1,  Jesse Wong 1,  Paul McNamara 1,  Andrew Prongay 1,  Vincent Madison 1,  John J Piwinski 1,  Kuo-Chi Cheng 1,  Richard Morrison 1,  Bruce Malcolm 1,  Xiao Tong 1,  Robert Ralston 1,  F George Njoroge 1
Affiliations

Affiliation

  • 1 Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
PMID: 24900178 DOI: 10.1021/ml9000276
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.

Keywords

Hepatitis C virus NS3 serine protease inhibitor; SCH 900518; narlaprevir; α-ketoamide.

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