Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors

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• 作者：Eda Canales^a ; ^{eda.canales@gilead.com} ; Joseph S. Carlson^a ; ^&dagger ; ; Todd Appleby^b ; Martijn Fenaux^c ; ^&Dagger ; ; Johnny Lee^d ; Yang Tian^d ; Neeraj Tirunagari^d ; Melanie Wong^c ; William J. Watkins^a
• 关键词：Amide bioisostere ; HCV ; Thumb ; PDB ; Hydrazine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 July, 2012
• 卷：22
• 期：13
• 页码：4288-4292
• 文件大小：459 K

摘要

The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement generated an analog with similar conformational and physicochemical properties. The series was extended to produce compounds with potent binding affinities and encouraging levels of cellular potency.