Abstract
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay.
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / metabolism*
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Amyloid beta-Protein Precursor / antagonists & inhibitors
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Combinatorial Chemistry Techniques*
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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 / pharmacology*
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Molecular Structure
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Structure-Activity Relationship
Substances
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Amyloid beta-Protein Precursor
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Ethylamines
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Aspartic Acid Endopeptidases
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ethylamine