Macrocyclic Inhibitors of the NS3 Protease as Potential Therapeutic Agents of Hepatitis C Virus Infection

Youla S. Tsantrizos, Gordon T. Bolger, Pierre Bonneau, Dale R. Cameron, Nathalie Goudreau, George Kukolj, Steven R. LaPlante, Montse Llinàs‐Brunet, Herbert Nar, Daniel Lamarre

Angewandte Chemie International Edition · 2003 · 188 citations · 21 references

Concepts

Abstract

Clinically useful antiviral agents for the treatment of hepatitis C viral infections might be derived from the here presented macrocyclic inhibitors (right) of the hepatitis C virus (HCV) NS3 protease. The NMR-derived conformation of a substrate-based enzyme-bound hexapeptide (left) was used to design these inhibitors. These are the first inhibitors of NS3 protease which block HCV RNA replication in the cell-based replicon assay, they are orally absorbed, and they are stable to metabolic breakdown. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2003/z50274_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

References

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