Abstract
The subtle modification of a selection of Abeta42 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining Abeta42 inhibition. Methylflurbiprofen 6 exhibited similar in vitro Abeta42 inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer's disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development.
MeSH terms
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Administration, Oral
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Alzheimer Disease / drug therapy*
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Amyloid beta-Peptides / antagonists & inhibitors*
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Brain / drug effects*
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Brain / metabolism
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / pharmacology
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Cyclooxygenase Inhibitors / therapeutic use
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Disease Models, Animal
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Flurbiprofen / analogs & derivatives
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Flurbiprofen / chemical synthesis*
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Flurbiprofen / pharmacology
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Flurbiprofen / therapeutic use
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Mice
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Peptide Fragments / antagonists & inhibitors*
Substances
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Amyloid beta-Peptides
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase Inhibitors
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Peptide Fragments
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amyloid beta-protein (1-42)
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Flurbiprofen