HCV NS3 serine protease inhibitors: Discovery of carbamate derived new P4 capping moieties with improved profile

MEDI 84

A. Arasappan, ashok.arasappan@spcorp.com1, A. I. Padilla1, F. Bennett1, S. L. Bogen1, Kevin X Chen, kevin.chen@spcorp.com1, S. Hendrata1, Y. Huang1, Edwin Jao1, W. Pan1, R. E. Pike1, S. Ruan1, M. Sannigrahi, S. Venkatraman1, B. Vibulbhan1, Wanli Wu1, W. Yang1, A. K. Saksena1, V. Girijavallabhan1, Xiao Tong2, K-C. Cheng3, N-Y. Shih1, and F. G. Njoroge1. (1) Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Rd, K-15-3-3545, Kenilworth, NJ 07033, (2) Virology, Schering-Plough Research Institute, 2015 Galloping Hill Rd, K-15-3, Kenilworth, NJ 07033, (3) Drug Metabolism, Schering-Plough Research Institute
Hepatitis C virus (HCV) infection is a global health crisis leading to liver cirrhosis, hepatocellular carcinoma and liver failure in humans. An estimated 3% of the human population is infected with HCV. The major goal of our research program was to develop new, specifically-targeted, orally active, NS3 serine protease inhibitors that could be developed as effective anti-HCV drug candidate to improve the virologic response. Proof of concept studies in humans with HCV NS3 serine protease inhibitors has validated this hypothesis. Our recent efforts in this area were directed towards improving the overall profile of the inhibitors. In this poster we will elaborate on our studies leading to the discovery of carbamate-derived new P4 moieties that resulted in inhibitors with enhanced potency and improved rat oral bioavailability.
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007