Synthesis of potent and broad genotypically active NS5B HCV non-nucleoside inhibitors binding to the thumb domain allosteric site 2 of the viral polym...
Basic Information
ID: ALA4431344
Journal: Bioorg Med Chem Lett
Title: Synthesis of potent and broad genotypically active NS5B HCV non-nucleoside inhibitors binding to the thumb domain allosteric site 2 of the viral polymerase.
Authors: Pierra Rouvière C, Amador A, Badaroux E, Convard T, Da Costa D, Dukhan D, Griffe L, Griffon JF, LaColla M, Leroy F, Liuzzi M, Loi AG, McCarville J, Mascia V, Milhau J, Onidi L, Paparin JL, Rahali R, Sais E, Seifer M, Surleraux D, Standring D, Dousson C.
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.
CiteXplore: 27520942
DOI: 10.1016/j.bmcl.2016.01.042
Patent ID: ┄