Abstract
Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4c displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b) <10 nM; EC(50) (1b)=34 nM) as well as good stability towards human liver microsomes (HLM t(1/2) =59 min).
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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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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Drug Design
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Hepacivirus / drug effects*
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Humans
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Microsomes, Liver / drug effects*
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Molecular Structure
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology*
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Structure-Activity Relationship
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Viral Nonstructural Proteins / antagonists & inhibitors*
Substances
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Antiviral Agents
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Pyridazines
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus