Abstract
A new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1' group of the compounds, efficient inhibitors were obtained with Ki down to 2.3 nM and EC50 down to 0.17 microM. Two inhibitor-enzyme X-ray structures are reported.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alcohols / chemistry*
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Binding Sites
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Carbamates / chemical synthesis*
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Carbamates / chemistry
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Carbamates / pharmacology
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Cell Line
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Crystallography, X-Ray
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HIV Protease Inhibitors / chemical synthesis*
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HIV Protease Inhibitors / chemistry
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HIV Protease Inhibitors / pharmacology
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HIV-1 / drug effects*
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HIV-1 / enzymology
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Humans
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Hydrazines / chemical synthesis*
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Hydrazines / chemistry
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Hydrazines / pharmacology
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Models, Molecular*
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Molecular Mimicry
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Oxadiazoles / chemical synthesis
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Oxadiazoles / chemistry
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Oxadiazoles / pharmacology
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Pyridines / chemical synthesis
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Pyridines / chemistry
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Pyridines / pharmacology
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Stereoisomerism
Substances
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(1-(N'-(4-hydroxy-4-(2-hydroxyindan-1-ylcarbamoyl)-5-phenylpentyl)-N'-(4-pyridin-4-ylbenzyl)hydrazinocarbonyl)-2,2-dimethylpropyl)carbamic acid methyl ester
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Alcohols
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Carbamates
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HIV Protease Inhibitors
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Hydrazines
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Imidazoles
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Oxadiazoles
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Pyridines
Associated data
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PDB/2BQV
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PDB/2UXZ
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PDB/2UY0