Discovery of γ-secretase inhibitors efficacious in a transgenic animal model of Alzheimer's disease
2007
Abstract Attachment of the cyclopropylcarbamate group to the piperidine core of γ-secretase inhibitors leads to a dramatic increase of their in vitro potency. Strategies for subsequent improvement of the in vivo pharmacokinetic profile of the series are discussed. Resulting compounds significantly reduce Aβ levels in TgCRND8 mice after a single PO dosing at 30 mpk.
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