Abstract
A novel norstatine derivative, phenylthionorstatine [(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; Ptns], containing a hydroxymethylcarbonyl (HMC) isostere was designed, synthesized, and stereochemically determined. Then, Ptns was introduced into the structure of BACE1 inhibitors at the P(1) position. Finally, Ptns was found as a suitable P(1) moiety for potent BACE1 inhibitor design.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminocaproates / chemistry*
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Aminocaproates / pharmacology*
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Butyrates / chemical synthesis*
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Butyrates / pharmacology*
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Chromatography, High Pressure Liquid
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Indicators and Reagents
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Molecular Conformation
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Spectrometry, Mass, Fast Atom Bombardment
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Structure-Activity Relationship
Substances
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(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid
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Aminocaproates
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Butyrates
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Enzyme Inhibitors
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Indicators and Reagents
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3-amino-2-hydroxy-5-methylhexanoic acid
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human