Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371122 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.
Graphical abstractStructure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provide possible explanations for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.Figure optionsDownload full-size imageDownload as PowerPoint slide