Abstract
Further SAR studies on the thiophene-2-carboxylic acids are reported. These studies led to the identification of a series of tertiary amides that show inhibition of both HCV NS5B polymerase in vitro and HCV subgenomic RNA replication in Huh-7 cells. Structural insights about the bioactive conformation of this class of molecules were deduced from a combination of modeling and transferred NOE (trNOE) studies.
MeSH terms
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Amides / chemistry
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Amides / pharmacology*
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Carboxylic Acids
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Carcinoma, Hepatocellular / chemistry
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Carcinoma, Hepatocellular / enzymology
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Carcinoma, Hepatocellular / virology
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Genome, Viral
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Hepacivirus / enzymology*
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Humans
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Liver Neoplasms / chemistry
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Liver Neoplasms / enzymology
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Liver Neoplasms / virology
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Magnetic Resonance Spectroscopy
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Molecular Conformation
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Molecular Structure
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RNA, Viral / metabolism*
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RNA-Dependent RNA Polymerase / antagonists & inhibitors
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Replicon / drug effects
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Structure-Activity Relationship
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Thiophenes / chemistry
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Thiophenes / pharmacology*
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Virus Replication / drug effects
Substances
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Amides
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Carboxylic Acids
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Enzyme Inhibitors
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RNA, Viral
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Thiophenes
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Viral Nonstructural Proteins
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2-thiophene carboxylic acid
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NS-5 protein, hepatitis C virus
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RNA-Dependent RNA Polymerase