Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370814 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
Abstract
Replacement of the benzimidazole core of allosteric Thumb Pocket 1 HCV NS5B finger loop inhibitors by more lipophilic indole derivatives provided up to 30-fold potency improvements in cell-based subgenomic replicon assays. Optimization of C-2 substitution on the indole core led to the identification of analogs with EC50 <100 nM and modulated the pharmacokinetic properties of the inhibitors based on preliminary data from in vitro ADME profiles and in vivo rat PK.
Graphical abstractHepatitis C virus antiviral HCV NS5B polymerase inhibitor SAR.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Authors
Pierre L. Beaulieu, James Gillard, Eric Jolicoeur, Jianmin Duan, Michel Garneau, George Kukolj, Marc-André Poupart,