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.

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Bibliographic Details
Published in:	Organic 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
Language:	English
Published:	United States American Chemical Society 27-11-2003
Subjects:	Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Crystallography, X-Ray Hepacivirus - drug effects Hepacivirus - enzymology Hepacivirus - physiology Inhibitory Concentration 50 Lactams - chemistry Molecular Conformation Molecular Structure Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Pyrrolidines - chemistry Urea - chemistry Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - metabolism Virus Replication - drug effects
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Description
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