5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase.
Ellis, D.A., Blazel, J.K., Tran, C.V., Ruebsam, F., Murphy, D.E., Li, L.S., Zhao, J., Zhou, Y., McGuire, H.M., Xiang, A.X., Webber, S.E., Zhao, Q., Han, Q., Kissinger, C.R., Lardy, M., Gobbi, A., Showalter, R.E., Shah, A.M., Tsan, M., Patel, R.A., LeBrun, L.A., Kamran, R., Bartkowski, D.M., Nolan, T.G., Norris, D.A., Sergeeva, M.V., Kirkovsky, L.(2009) Bioorg Med Chem Lett 19: 6047-6052
- PubMed: 19796938
- DOI: https://doi.org/10.1016/j.bmcl.2009.09.051
- Primary Citation of Related Structures:
3GYN, 3IGV - PubMed Abstract:
The discovery of 5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC50 <0.10 microM). In vitro DMPK data for selected compounds as well as crystal structures of representative inhibitors complexed with the NS5B protein are also disclosed.
Organizational Affiliation:
Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.