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Macrocyclic Inhibitors of the NS3 Protease as Potential Therapeutic Agents of Hepatitis C Virus Infection
Author(s) -
Tsantrizos Youla S.,
Bolger Gordon,
Bonneau Pierre,
Cameron Dale R.,
Goudreau Nathalie,
Kukolj George,
LaPlante Steven R.,
LlinàsBrunet Montse,
Nar Herbert,
Lamarre Daniel
Publication year - 2003
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200390347
Subject(s) - ns3 , protease , hepatitis c virus , replicon , virology , ns2 3 protease , enzyme , virus , viral replication , hepatitis c , chemistry , rna , hepacivirus , hepatitis virus , biochemistry , biology , dna , gene , plasmid
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.