Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Studies leading to the identification of the orally active γ-secretase inhibitor
32 are described. This compound demonstrated lowering of central Aβ(40) in a rodent model with a MED of 1
mg/kg.
The protease γ-secretase plays a pivotal role in the synthesis of pathogenic amyloid-β in Alzheimer’s disease (AD). Here, we report a further extension to a series of cyclohexyl sulfone-based γ-secretase inhibitors which has allowed the preparation of highly potent compounds which also demonstrate robust Aβ(40) lowering in vivo (e.g., compound
32, MED 1
mg/kg p.o. in APP-YAC mice).