Abstract
A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core structure with different prime side alkyl substituted 4,5,6,7-tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized. Striking differences were observed on potencies in the BACE-1 enzymatic and cellular assays depending on the nature of the heteroatoms in the bicyclic ring, from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of 44 nM (enzyme assay) and 65 nM (cell-based assay).
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Animals
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Azoles / chemical synthesis*
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Azoles / chemistry
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Azoles / pharmacology
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Benzoxazoles / chemical synthesis*
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacology
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Catalytic Domain
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Crystallography, X-Ray
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Drug Design*
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Ethylamines / chemical synthesis*
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Ethylamines / chemistry
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Ethylamines / pharmacology
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Humans
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Inhibitory Concentration 50
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Male
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Mice
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Mice, Inbred C57BL
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Models, Molecular
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Molecular Structure
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
Substances
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Azoles
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Benzoxazoles
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Enzyme Inhibitors
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Ethylamines
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Pyridines
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human