Abstract
A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.
MeSH terms
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Genotype*
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Hepacivirus / drug effects*
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Hepacivirus / genetics
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Hepacivirus / physiology
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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Replicon / drug effects*
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Spectrometry, Mass, Electrospray Ionization
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Virus Replication / drug effects*
Substances
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Antiviral Agents
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Protease Inhibitors
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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