Download MendeleySynthesis of potent and broad genotypically active NS5B HCV non-nucleoside inhibitors binding to the thumb domain allosteric site 2 of the viral polymerase.
Pierra Rouviere, C., Amador, A., Badaroux, E., Convard, T., Da Costa, D., Dukhan, D., Griffe, L., Griffon, J.F., LaColla, M., Leroy, F., Liuzzi, M., Loi, A.G., McCarville, J., Mascia, V., Milhau, J., Onidi, L., Paparin, J.L., Rahali, R., Sais, E., Seifer, M., Surleraux, D., Standring, D., Dousson, C.(2016) Bioorg Med Chem Lett 26: 4536-4541
- PubMed: 27520942
- DOI: https://doi.org/10.1016/j.bmcl.2016.01.042
- Primary Citation of Related Structures:
5CZB - PubMed 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.
Organizational Affiliation:
Idenix SARL, an MSD Company, Medicinal Chemistry Laboratory, Cap Gamma, 1682 rue de la Valsière, BP 50001, 34189 Montpellier Cedex 4, France. Electronic address: claire.pierra-rouviere@merck.com.
