Structure−Activity Study on a Novel Series of Macrocyclic Inhibitors of the Hepatitis C Virus NS3 Protease Leading to the Discovery of BILN 2061
Journal of Medicinal Chemistry2004Vol. 47(7), pp. 1605–1608
Citations Over TimeTop 10% of 2004 papers
Montse Llinàs‐Brunet, Murray D. Bailey, Gordon T. Bolger, Christian Brochu, Anne‐Marie Faucher, Jean Marie Ferland, Michel Garneau, Élise Ghiro, Vida Gorys, Chantal Grand‐Maître, Ted Halmos, Nicole Lapeyre-Paquette, Francine Liard, Martin Poirier, Manon Rhéaume, Youla S. Tsantrizos, Daniel Lamarre
Abstract
From the discovery of competitive hexapeptide inhibitors, potent and selective HCV NS3 protease macrocyclic inhibitors have been identified. Structure-activity relationship studies were performed focusing on optimizing the N-terminal carbamate and the aromatic substituent on the (4R)-hydroxyproline moiety. Inhibitors meeting the potency criteria in the cell-based assay and with improved oral bioavailability in rats were identified. BILN 2061 was selected as the best compound, the first NS3 protease inhibitor reported with antiviral activity in man.
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