Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ⁶-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones: Part 4. Optimization of DMP

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• 作者：Maria V. Sergeeva ; Yuefen Zhou ; Darian M. Bartkowski ; Thomas G. Nolan ; Daniel A. Norris ; Ellen Okamoto ; Leo Kirkovsky ; Ruhi Kamran ; Laurie A. LeBrun ; Mei Tsan ; Rupal Patel ; Amit M. Shah ; Matthew Lardy
• 关键词：Pyridazinones ; 5-Hydroxy-3(2H)-pyridazinone derivatives ; Hepatitis C virus (HCV) ; RNA-dependent RNA polymerase (RdRp) ; Small molecule ; Non-nucleoside NS5B inhibitors ; DMPK properties
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：1 June 2008
• 年：2008
• 卷：18
• 期：11
• 页码：3421-3426
• 全文大小：249 K

文摘

5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties.