Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: From benzimidazole to indole scaffolds

Autor:	Jeffrey M. Warrington, Lisette Lagacé, Christian Brochu, Louise Thauvette, Steven R. LaPlante, Bruno Haché, Darren Bykowski, Pierre L. Beaulieu, George Kukolj, James Gillard, Stéphane Perreault, Araz Jakalian, Timothy A. Stammers, Ginette McKercher, Nathalie Dansereau, Jean-Simon Duceppe, Elaine Moreau
Rok vydání:	2006
Předmět:	Benzimidazole Indoles Hepatitis C virus Clinical Biochemistry Allosteric regulation Pharmaceutical Science Hepacivirus Viral Nonstructural Proteins medicine.disease_cause Biochemistry Cell Line Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Allosteric Regulation Drug Discovery medicine Humans Replicon Molecular Biology Subgenomic mRNA Indole test chemistry.chemical_classification Chemistry Organic Chemistry virus diseases RNA-Dependent RNA Polymerase Nucleotidyltransferase digestive system diseases Enzyme Molecular Medicine Benzimidazoles
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 16:4987-4993
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2006.07.074
Popis:	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 (EC(50) approximately 50 nM).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cdb0f56a825782ec52e9f587144ae60d https://doi.org/10.1016/j.bmcl.2006.07.074 Zobrazit plný text záznamu Full Text from ScienceDirect