Abstract
The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1.
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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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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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / chemistry
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Aspartic Acid Endopeptidases / metabolism*
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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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Humans
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Models, Molecular
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology*
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Protein Binding
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Structure-Activity Relationship
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Ethylamines
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Protease Inhibitors
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human