N-Acetamideindolecarboxylic acid allosteric ‘finger-loop’ inhibitors of the hepatitis C virus NS5B polymerase: discovery and initial optimization studies

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• 作者：Pierre L. Beaulieu ; Eric Jolicoeur ; James Gillard ; Christian Brochu ; René ; Coulombe ; Nathalie Dansereau ; Jianmin Duan ; Michel Garneau ; Araz Jakalian ; Peter Kü ; hn ; Lisette Lagacé ; Steven L
• 关键词：HCV NS5B polymerase ; HCV replicon inhibitors ; Allosteric inhibitors ; Antivirals ; Hepatitis C virus
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 February 2010
• 年：2010
• 卷：20
• 期：3
• 页码：857-861
• 全文大小：1383 K

文摘

SAR studies at the N¹-position of allosteric indole-based HCV NS5B inhibitors has led to the discovery of acetamide derivatives with good cellular potency in subgenomic replicons (EC₅₀ <200 nM). This class of inhibitors displayed improved physicochemical properties and favorable ADME-PK profiles over previously described analogs in this class.