Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency

A Arasappan; F G Njoroge; T-Y Chan; F Bennett; S L Bogen; K Chen; H Gu; L Hong; E Jao; Y-T Liu; R G Lovey; T Parekh; R E Pike; P Pinto; B Santhanam; S Venkatraman; H Vaccaro; H Wang; X Yang; Z Zhu; B Mckittrick; A K Saksena; V Girijavallabhan; J Pichardo; N Butkiewicz; R Ingram; B Malcolm; A Prongay; N Yao; B Marten; V Madison; S Kemp; O Levy; M Lim-Wilby; S Tamura; A K Ganguly

doi:10.1016/j.bmcl.2005.06.091

Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4180-4. doi: 10.1016/j.bmcl.2005.06.091.

Authors

Affiliation

¹ Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ashok.arasappan@spcorp.com

PMID: 16087332
DOI: 10.1016/j.bmcl.2005.06.091

Abstract

We have discovered that introduction of appropriate amino acid derivatives at P'2 position improved the binding potency of P3-capped alpha-ketoamide inhibitors of HCV NS3 serine protease. X-ray crystal structure of one of the inhibitors (43) bound to the protease revealed the importance of the P'2 moiety.

MeSH terms

Binding Sites
Crystallography, X-Ray
Hepacivirus / chemistry*
Molecular Structure
Protein Binding
Serine Proteinase Inhibitors / chemistry*
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / chemistry

Substances

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

Associated data

PDB/2A4G