Abstract
A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases.
MeSH terms
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Animals
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Benzofurans* / chemical synthesis
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Benzofurans* / chemistry
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Benzofurans* / pharmacology
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Cell Line, Tumor
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Chlorocebus aethiops
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Drug Design
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Drug Evaluation, Preclinical
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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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Humans
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Molecular Structure
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Pyrans* / chemical synthesis
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Pyrans* / chemistry
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Pyrans* / pharmacology
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RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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RNA-Dependent RNA Polymerase / chemistry
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Structure-Activity Relationship
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Vero Cells
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / chemistry
Substances
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Benzofurans
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Enzyme Inhibitors
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Pyrans
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus
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RNA-Dependent RNA Polymerase