Abstract
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The structure-activity relationship (SAR) associated with variation of the pyridazinone 2- and 6-substituents is discussed. The synthesis and metabolic stability of this new class of compounds are also described.
MeSH terms
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Crystallography, X-Ray
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Drug Design
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Drug Stability
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Microsomes, Liver / metabolism
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Models, Molecular
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Pyridazines / chemical synthesis
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Pyridazines / chemistry*
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Pyridazines / pharmacology*
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RNA-Dependent RNA Polymerase / antagonists & inhibitors
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RNA-Dependent RNA Polymerase / metabolism
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Thiadiazines / chemical synthesis
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Thiadiazines / chemistry
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Thiadiazines / pharmacology
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / metabolism
Substances
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Enzyme Inhibitors
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Pyridazines
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Thiadiazines
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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