| Literature DB >> 19818610 |
Frank Ruebsam1, Douglas E Murphy, Chinh V Tran, Lian-Sheng Li, Jingjing Zhao, Peter S Dragovich, Helen M McGuire, Alan X Xiang, Zhongxiang Sun, Benjamin K Ayida, Julie K Blazel, Sun Hee Kim, Yuefen Zhou, Qing Han, Charles R Kissinger, Stephen E Webber, Richard E Showalter, Amit M Shah, Mei Tsan, Rupal A Patel, Peggy A Thompson, Laurie A Lebrun, Huiying J Hou, Ruhi Kamran, Maria V Sergeeva, Darian M Bartkowski, Thomas G Nolan, Daniel A Norris, Julia Khandurina, Jennifer Brooks, Ellen Okamoto, Leo Kirkovsky.
Abstract
A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we identified a number of metabolically stable and very potent compounds in genotype 1a and 1b replicon assays. This work culminated in the discovery of several inhibitors, which combined potent in vitro antiviral activity against both 1a and 1b genotypes, metabolic stability, good oral bioavailability, and high C(12) (PO)/EC(50) ratios.Entities:
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Year: 2009 PMID： 19818610 DOI： 10.1016/j.bmcl.2009.09.045
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823