Abstract
Hepatitis C virus (HCV) NS5B polymerase is the key replicating protein of the virus and thus an attractive target for drug development. Here we report on the synthesis and biological evaluation of a new series of benzimidazole derivatives as HCV NS5B inhibitors. This yielded compound 6b and 6d bearing 2-(2-benzyloxy)phenyl and 2-(4-methylbenzyloxy)phenyl moieties, respectively, as promising leads. Binding mode of compound 6d in allosteric pocket (AP)-1 of NS5B will form the basis for future structure-activity relationship optimization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology*
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DNA-Directed RNA Polymerases / antagonists & inhibitors*
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Drug Design*
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Hepacivirus / drug effects*
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Quantitative Structure-Activity Relationship
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Structure-Activity Relationship
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Viral Nonstructural Proteins / drug effects*
Substances
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Benzimidazoles
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Enzyme Inhibitors
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Viral Nonstructural Proteins
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benzimidazole
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NS-5 protein, hepatitis C virus
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DNA-Directed RNA Polymerases