Autor: |
Jingjing Zhao, Frank Ruebsam, Rupal Patel, Douglas E. Murphy, Tran Chinh Viet, Stephen E. Webber, Charles R. Kissinger, Nebojsa Stankovic, Lian-Sheng Li, Darian M. Bartkowski, Richard E. Showalter, Qiang Zhao, Mei Tsan, Benjamin K. Ayida, Zhongxiang Sun, Ruhi Kamran, Leo Kirkovsky, Peter S. Dragovich, Jennifer Brooks, Amit M. Shah, Laurie A. LeBrun, Maria V. Sergeeva, Thomas M. Bertolini, Thomas G. Nolan, Daniel A. Norris, Yuefen Zhou |
Rok vydání: |
2008 |
Předmět: |
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Zdroj: |
Bioorganicmedicinal chemistry letters. 18(11) |
ISSN: |
1464-3405 |
Popis: |
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 [IC(50) (1b)10nM; IC(50) (1a)=22 nM; EC(50) (1b)=5nM], good stability toward human liver microsomes (HLM t(1/2)60 min), and high ratios of liver to plasma concentrations 12h after a single oral administration to rats. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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