Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity

Stéphane L Bogen; Sumei Ruan; Rong Liu; Sony Agrawal; John Pichardo; Andrew Prongay; Bahige Baroudy; Anil K Saksena; Viyyoor Girijavallabhan; F George Njoroge

doi:10.1016/j.bmcl.2005.12.013

Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1621-7. doi: 10.1016/j.bmcl.2005.12.013. Epub 2006 Jan 4.

Authors

Stéphane L Bogen¹, Sumei Ruan, Rong Liu, Sony Agrawal, John Pichardo, Andrew Prongay, Bahige Baroudy, Anil K Saksena, Viyyoor Girijavallabhan, F George Njoroge

Affiliation

¹ Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 16387495
DOI: 10.1016/j.bmcl.2005.12.013

Abstract

Depeptidization efforts of the P(3)-P(2) region of P(3) capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 are reported. We clearly established that N-methylation of the P(2) nitrogen and modification of the P(2)' carboxylic acid terminus were essential for activity in the replicon assay.

MeSH terms

Amides* / chemical synthesis
Amides* / chemistry
Amides* / pharmacology
Binding Sites
Hepacivirus / chemistry
Hepacivirus / drug effects*
Hepacivirus / enzymology
Methylation
Molecular Structure
Nitrogen / chemistry*
Protein Binding
Replicon / drug effects*
Serine Proteinase Inhibitors* / chemical synthesis
Serine Proteinase Inhibitors* / chemistry
Serine Proteinase Inhibitors* / pharmacology
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / chemistry
X-Ray Diffraction

Substances

Amides
NS3 protein, hepatitis C virus
Serine Proteinase Inhibitors
Viral Nonstructural Proteins
Nitrogen