Abstract
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Alzheimer Disease / drug therapy
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Amyloid Precursor Protein Secretases / chemistry
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Amyloid Precursor Protein Secretases / metabolism
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Animals
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Arginine / chemistry*
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Binding Sites
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Computer Simulation
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Crystallography, X-Ray
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Ethylamines / chemical synthesis
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Ethylamines / chemistry*
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Ethylamines / therapeutic use
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry*
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Protease Inhibitors / therapeutic use
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Rats
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Structure-Activity Relationship
Substances
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Ethylamines
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Protease Inhibitors
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Arginine
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Amyloid Precursor Protein Secretases