MEDI 88

Discovery of Novel P4 capped sulfonamide derived inhibitors of HCV NS3 protease

Srikanth Venkatraman, Srikanth.Venkatraman@spcorp.com¹, Wanli Wu², Melissa Blackman³, Ashok Arasappan², Frank Bennett², Stephane L Bogen, stephane.bogen@spcorp.com², Kevin X Chen, kevin.chen@spcorp.com², Siska Hendrata¹, Yuhua Huang², Edwin Jao², Latha Nair², A. I. Padilla², Weidong Pan², R. Pike², Patrick Pinto², S. Ruan², Mousumi Sannigrahi², Francisco Velazquez², Bancha Vibulbhan², Weiying Yang², Anil Saksena², Viyyoor Girijvallabhan³, Xiao Tong⁴, K-C. Cheng⁵, Neng-Yang Shih⁶, and F. George Njoroge². (1) Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, A-301, MS 3545, Kenilworth, NJ 07033, (2) Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Rd, K-15-3-3545, Kenilworth, NJ 07033, (3) Chemical Research Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3 3545, Kenilworth, NJ 07033-1300, (4) Virology, Schering-Plough Research Institute, 2015 Galloping Hill Rd, K-15-3, Kenilworth, NJ 07033, (5) Drug Metabolism, Schering-Plough Research Institute, (6) Schering-Plough Research Institute

Hepatitis C Virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 200 million, people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or 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 genotype 1 and relapse patients is moderate at best, with only about 40% of the patients showing sustained virological response. Lack of effective methods to treat chronic HCV infections, and patients relapsing from interferon therapy necessitates discovery of new drugs. Significant efforts are now directed towards development of therapies that target key enzymes vital to HCV replication and maturation. In this presentation we discuss, the identification of novel P3 sulfonamide capped ketoamide inhibitors that exhibit excellent binding in NS3 enzyme assay and replicon cellular assay.

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