Abstract
The evolution of amide 3 into conformationally restricted bicyclic triazolo-piperidine 14-S as a γ-secretase modulator is described. This is a potential disease modifying anti-Alzheimer's drug which demonstrated high in vitro and in vivo potency against Aβ42 peptide, reduced lipophilicity and enhanced brain free fraction compared to the previous series.
Keywords:
Alzheimer’s disease; γ-Secretase modulators.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / enzymology*
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Amyloid Precursor Protein Secretases / metabolism*
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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Dogs
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Drug Design*
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Humans
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Mice
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Microsomes, Liver / metabolism
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Models, Molecular
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Piperidines / chemistry
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Piperidines / metabolism
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Piperidines / pharmacology*
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Triazoles / chemistry
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Triazoles / metabolism
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Triazoles / pharmacology*
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Piperidines
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Triazoles
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Amyloid Precursor Protein Secretases