Abstract
5,6-Dihydro-1H-pyridin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4ad displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b)<10nM; IC(50) (1a)<25nM, EC(50) (1b)=16nM), good in vitro DMPK properties, as well as moderate oral bioavailability in monkeys (F=24%).
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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DNA-Directed RNA Polymerases / antagonists & inhibitors*
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Haplorhini
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Pyridones / administration & dosage
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Pyridones / chemistry
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Pyridones / pharmacokinetics
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Pyridones / pharmacology*
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Structure-Activity Relationship
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Viral Nonstructural Proteins / antagonists & inhibitors*
Substances
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Enzyme Inhibitors
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Pyridones
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus
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DNA-Directed RNA Polymerases