Abstract
In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9, 10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing.
Keywords:
Alzheimer’s disease; Aminopyridopyrimidines; Aβ production; Notch-processing; γ-Secretase inhibitors.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Amyloid beta-Peptides / antagonists & inhibitors
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Animals
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Humans
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Microsomes, Liver / metabolism
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Peptide Fragments / antagonists & inhibitors
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / pharmacology*
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Pyridones / chemical synthesis
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Pyridones / pharmacology*
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Pyrimidines / chemical synthesis
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Pyrimidines / pharmacology*
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Rats
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Receptor, Notch1 / metabolism*
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Structure-Activity Relationship
Substances
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Amyloid beta-Peptides
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NOTCH1 protein, human
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Notch1 protein, rat
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Peptide Fragments
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Protease Inhibitors
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Pyridones
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Pyrimidines
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Receptor, Notch1
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amyloid beta-protein (1-40)
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Amyloid Precursor Protein Secretases