Abstract
A series of macrocyclic compounds containing 2-substituted-quinoline moieties have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K mutant activity while maintaining the high rat liver exposure. Cyclization of the 2-substituted quinoline substituent led to a series of tricyclic P2 compounds which also display superb gt3a potency.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Carrier Proteins / antagonists & inhibitors*
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Carrier Proteins / metabolism
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Cyclization
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Genotype
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Half-Life
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Hepacivirus / enzymology*
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Hepacivirus / genetics
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Intracellular Signaling Peptides and Proteins
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Kinetics
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Liver / metabolism
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Macrocyclic Compounds / chemical synthesis
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Macrocyclic Compounds / chemistry*
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Macrocyclic Compounds / pharmacokinetics
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacokinetics
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Quinolines / chemistry
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Rats
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Structure-Activity Relationship
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / metabolism
Substances
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Macrocyclic Compounds
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NS3 protein, hepatitis C virus
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NS4A cofactor peptide, Hepatitis C virus
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Protease Inhibitors
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Quinolines
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Viral Nonstructural Proteins
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quinoline