Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369436 | Bioorganic & Medicinal Chemistry Letters | 2016 | 6 Pages |
Abstract
The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells and, as a consequence, is an attractive target for selective inhibition. This Letter describes the discovery of a new family of HCV NS5B non-nucleoside inhibitors, based on the bioisosterism between amide and phosphonamidate functions. As part of this program, SAR in this new series led to the identification of IDX17119, a potent non-nucleoside inhibitor, active on the genotypes 1b, 2a, 3a and 4a. The structure and binding domain of IDX17119 were confirmed by X-ray co-crystallization study.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Claire Pierra Rouvière, Agnès Amador, Eric Badaroux, Thierry Convard, Daniel Da Costa, David Dukhan, Ludovic Griffe, Jean-François Griffon, Massimiliano LaColla, Frédéric Leroy, Michel Liuzzi, Anna Giulia Loi, Joe McCarville, Valeria Mascia,