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  • Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection.

Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection.

Journal of medicinal chemistry (2006-09-29)
Srikanth Venkatraman, Stéphane L Bogen, Ashok Arasappan, Frank Bennett, Kevin Chen, Edwin Jao, Yi-Tsung Liu, Raymond Lovey, Siska Hendrata, Yuhua Huang, Weidong Pan, Tejal Parekh, Patrick Pinto, Veljko Popov, Russel Pike, Sumei Ruan, Bama Santhanam, Bancha Vibulbhan, Wanli Wu, Weiying Yang, Jianshe Kong, Xiang Liang, Jesse Wong, Rong Liu, Nancy Butkiewicz, Robert Chase, Andrea Hart, Sony Agrawal, Paul Ingravallo, John Pichardo, Rong Kong, Bahige Baroudy, Bruce Malcolm, Zhuyan Guo, Andrew Prongay, Vincent Madison, Lisa Broske, Xiaoming Cui, Kuo-Chi Cheng, Yunsheng Hsieh, Jean-Marc Brisson, Danial Prelusky, Walter Korfmacher, Ronald White, Susan Bogdanowich-Knipp, Anastasia Pavlovsky, Prudence Bradley, Anil K Saksena, Ashit Ganguly, John Piwinski, Viyyoor Girijavallabhan, F George Njoroge
PMID17004721
ABSTRACT

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.