Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCVNS5B polymerase:: From benzimidazole to indole scaffolds

Benzimidazole-based allosteric inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified to a variety of topologically related scaffolds. Replacement of the polar benzimidazole core by lipophilic indoles led to inhibitors with improved potency in the cell-based subgenomic HCV replicon system. Transposing the indole scaffold into a previously described series of benzimidazole tryptophan amides generated the most potent inhibitors of HCV RNA replication in cell culture reported to date in this series (EC50 similar to 50 nM). (c) 2006 Elsevier Ltd. All rights reserved.