SAR and pharmacokinetic studies on phenethylamide inhibitors of the hepatitis C virus NS3/NS4A serine protease

Savina Malancona; Stefania Colarusso; Jesus M Ontoria; Antonella Marchetti; Marco Poma; Ian Stansfield; Ralph Laufer; Annalise Di Marco; Marina Taliani; Maria Verdirame; Odalys Gonzalez-Paz; Victor G Matassa; Frank Narjes

doi:10.1016/j.bmcl.2004.05.093

SAR and pharmacokinetic studies on phenethylamide inhibitors of the hepatitis C virus NS3/NS4A serine protease

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4575-9. doi: 10.1016/j.bmcl.2004.05.093.

Authors

Savina Malancona¹, Stefania Colarusso, Jesus M Ontoria, Antonella Marchetti, Marco Poma, Ian Stansfield, Ralph Laufer, Annalise Di Marco, Marina Taliani, Maria Verdirame, Odalys Gonzalez-Paz, Victor G Matassa, Frank Narjes

Affiliation

¹ Department of Chemistry, Istituto di Ricerche di Biologia Molecolare, Merck Research Laboratories, Via Pontina Km 30.600, 00040 Pomezia, Rome, Italy.

PMID: 15357995
DOI: 10.1016/j.bmcl.2004.05.093

Abstract

SAR on the phenethylamide 1 (Ki 1.2 microM) in the P2- and the P'-position led to potent inhibitors, one of which showed good exposure and low clearance when administered intramuscularly to rat.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hepacivirus / drug effects
Hepacivirus / enzymology*
Phenethylamines / chemistry*
Phenethylamines / pharmacology
Rats
Serine Endopeptidases / pharmacokinetics*
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / pharmacokinetics*

Substances

NS3 protein, hepatitis C virus
NS4 protein, hepatitis C virus
Phenethylamines
Serine Proteinase Inhibitors
Viral Nonstructural Proteins
Serine Endopeptidases