Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1376652 | Bioorganic & Medicinal Chemistry Letters | 2008 | 10 Pages |
Abstract
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC50 (1b) < 10 nM; IC50 (1a) = 22 nM; EC50 (1b) = 5 nM], good stability toward human liver microsomes (HLM t1/2 > 60 min), and high ratios of liver to plasma concentrations 12 h after a single oral administration to rats.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Lian-Sheng Li, Yuefen Zhou, Douglas E. Murphy, Nebojsa Stankovic, Jingjing Zhao, Peter S. Dragovich, Thomas Bertolini, Zhongxiang Sun, Benjamin Ayida, Chinh V. Tran, Frank Ruebsam, Stephen E. Webber, Amit M. Shah, Mei Tsan, Richard E. Showalter,