Pyrrolidine-5,5-trans-lactams. 4. Incorporation of a P3/P4 Urea Leads to Potent Intracellular Inhibitors of Hepatitis C Virus NS3/4A Protease

In this, the first of two Letters, we describe how a P3/P4 urea linking unit was used to greatly enhance the biochemical and replicon potency of inhibitors based upon the pyrrolidine-5,5-trans-lactam template. Compound 7b demonstrated a 100 nM IC50 in the replicon cell-based surrogate HCV assay.

Saved in:
Bibliographic Details
Published inOrganic letters Vol. 5; no. 24; pp. 4627 - 4630
Main Authors Slater, Martin J, Amphlett, Elizabeth M, Andrews, David M, Bamborough, Paul, Carey, Seb J, Johnson, Martin R, Jones, Paul S, Mills, Gail, Parry, Nigel R, Stewart, Alan J, Skarzynski, Tadeusz
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 27.11.2003
Amer Chemical Soc
Subjects
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Chemistry
Chemistry, Organic
Crystallography, X-Ray
Hepacivirus - drug effects
Hepacivirus - enzymology
Hepacivirus - physiology
Inhibitory Concentration 50
Lactams - chemistry
Molecular Conformation
Molecular Structure
Physical Sciences
Protease Inhibitors - chemical synthesis
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Pyrrolidines - chemistry
Science & Technology
Urea - chemistry
Viral Nonstructural Proteins - antagonists & inhibitors
Viral Nonstructural Proteins - metabolism
Virus Replication - drug effects
INTERFERON-ALPHA-2B
DESIGN
REPLICATION
THERAPY
MOLECULAR VIROLOGY
RIBAVIRIN
COMBINATION
Online AccessGet full text

Cover

More Information
Summary:In this, the first of two Letters, we describe how a P3/P4 urea linking unit was used to greatly enhance the biochemical and replicon potency of inhibitors based upon the pyrrolidine-5,5-trans-lactam template. Compound 7b demonstrated a 100 nM IC50 in the replicon cell-based surrogate HCV assay.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol035826v