Abstract
Using a cell-based assay, we have identified a new series of Notch-sparing gamma-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved gamma-secretase inhibitory potency and Notch-sparing selectivity.
MeSH terms
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Alzheimer Disease / drug therapy
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Amyloid / chemistry
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Amyloid Precursor Protein Secretases / chemistry
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Carbon / chemistry
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Models, Chemical
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Receptors, Notch / antagonists & inhibitors
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Receptors, Notch / metabolism*
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Structure-Activity Relationship
Substances
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Amyloid
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Enzyme Inhibitors
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Receptors, Notch
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Carbon
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Amyloid Precursor Protein Secretases