Abstract
A new series of NS3/4A protease boronic acid inhibitors is described. The compounds show good biochemical potency and cellular activity. The peptidomimetic inhibitors were evaluated against proteases from different HCV genotypes and clinically relevant NS3/4A mutants. Compound 28 displayed subnanomolar to single digit nanomolar potencies in the enzymatic assays and an EC50 of 25 nM in the replicon cell-based assay.
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology
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Boronic Acids / chemical synthesis*
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Boronic Acids / chemistry
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Boronic Acids / pharmacology
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Carrier Proteins / antagonists & inhibitors*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Line, Tumor
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Genotype
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Hepacivirus / drug effects*
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Hepacivirus / genetics
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Hepatitis C / drug therapy
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Humans
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Intracellular Signaling Peptides and Proteins
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Mutant Proteins / antagonists & inhibitors
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Mutant Proteins / metabolism
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / metabolism
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Viral Proteins / antagonists & inhibitors*
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Viral Proteins / genetics
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Viral Proteins / metabolism
Substances
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Antiviral Agents
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Boronic Acids
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Mutant Proteins
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NS3 protein, hepatitis C virus
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NS4A cofactor peptide, Hepatitis C virus
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Protease Inhibitors
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Viral Nonstructural Proteins
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Viral Proteins