2. Academic Validation
  3. Structure-activity study on a novel series of macrocyclic inhibitors of the hepatitis C virus NS3 protease leading to the discovery of BILN 2061

Structure-activity study on a novel series of macrocyclic inhibitors of the hepatitis C virus NS3 protease leading to the discovery of BILN 2061

  • J Med Chem. 2004 Mar 25;47(7):1605-8. doi: 10.1021/jm0342414.
Montse Llinàs-Brunet 1,  Murray D Bailey,  Gordon Bolger,  Christian Brochu,  Anne-Marie Faucher,  Jean Marie Ferland,  Michel Garneau,  Elise Ghiro,  Vida Gorys,  Chantal Grand-Maître,  Ted Halmos,  Nicole Lapeyre-Paquette,  Francine Liard,  Martin Poirier,  Manon Rhéaume,  Youla S Tsantrizos,  Daniel Lamarre
Affiliations

Affiliation

  • 1 Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., 2100 Cunard Street, Laval, Québec H7S 2G5, Canada. mllinas@lav.boehringer-ingelheim.com
PMID: 15027850 DOI: 10.1021/jm0342414
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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