Abstract
In this work, we report a rational structure-based approach aimed at the discovery of new 2-aminoimidazoles as β-secretase inhibitors. Taking advantage of a microwave-assisted synthetic protocol, a small library of derivatives was obtained and biologically evaluated. Two compounds showed promising activities in both enzymatic and cellular assays. Moreover, one of them exhibited the capability to cross the blood-brain barrier as assessed by the parallel artificial membrane permeability assay.
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / enzymology
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Alzheimer Disease / metabolism
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Amyloid Precursor Protein Secretases / antagonists & inhibitors
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Amyloid Precursor Protein Secretases / metabolism*
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Amyloid beta-Peptides / metabolism
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Animals
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Cell Survival / drug effects
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Chickens
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacology*
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Inhibitory Concentration 50
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Neurons
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry*
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Small Molecule Libraries / pharmacology*
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Spectrometry, Mass, Electrospray Ionization
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Spectroscopy, Fourier Transform Infrared
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Structure-Activity Relationship
Substances
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Amyloid beta-Peptides
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Imidazoles
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Small Molecule Libraries
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Amyloid Precursor Protein Secretases