Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones

[Display omitted] 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 pyridopyrimidi...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2016-05, Vol.26 (9), p.2138-2141
Hauptverfasser: Zhang, Jing, Lu, Dai, Wei, Han-Xun, Gu, Yongli, Selkoe, Dennis J., Wolfe, Michael S., Augelli-Szafran, Corinne E.
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container_end_page 2141
container_issue 9
container_start_page 2138
container_title Bioorganic & medicinal chemistry letters
container_volume 26
creator Zhang, Jing
Lu, Dai
Wei, Han-Xun
Gu, Yongli
Selkoe, Dennis J.
Wolfe, Michael S.
Augelli-Szafran, Corinne E.
description [Display omitted] 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.
doi_str_mv 10.1016/j.bmcl.2016.03.077
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source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Alzheimer’s disease
Aminopyridopyrimidines
Amyloid beta-Peptides - antagonists & inhibitors
Amyloid Precursor Protein Secretases - antagonists & inhibitors
Animals
Aβ production
Humans
Microsomes, Liver - metabolism
Notch-processing
Peptide Fragments - antagonists & inhibitors
Protease Inhibitors - chemical synthesis
Protease Inhibitors - pharmacology
Pyridones - chemical synthesis
Pyridones - pharmacology
Pyrimidines - chemical synthesis
Pyrimidines - pharmacology
Rats
Receptor, Notch1 - metabolism
Structure-Activity Relationship
γ-Secretase inhibitors
title Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones
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