Abstract
The design, synthesis, and SAR of cyclic diamines as novel γ secretase modulators (GSMs) are presented in this Letter. Starting from information in the literature and in-house cyclic diamines library, we have found a 3(S)-aminopiperidine as a potent structure for lowering Aβ42 production both in vitro and in vivo.
Keywords:
Alzheimer’s disease; Amyloid β peptide; Piperidine; γ-Secretase inhibitor; γ-Secretase modulator.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Amyloid Precursor Protein Secretases / metabolism*
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / biosynthesis
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Dose-Response Relationship, Drug
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Drug Design*
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Humans
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Molecular Structure
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / biosynthesis
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Piperidines / chemical synthesis
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Piperidines / chemistry
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Piperidines / pharmacology*
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Structure-Activity Relationship
Substances
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Amyloid beta-Peptides
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Peptide Fragments
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Piperidines
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amyloid beta-protein (1-42)
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Amyloid Precursor Protein Secretases