γ-Secretase is one of the critical enzymes required for the generation of Aβ peptides, which play a key role in Alzheimer’s disease (AD). Inhibition of γ-secretase holds promise as a disease-modifying therapy for this disorder. This poster describes the synthesis, SAR, and biological profiles of a novel spiro heterocyclic series of γ-secretase inhibitors. A few representatives of the series were assessed in a non-transgenic animal model of AD and demonstrated reduction of Aβ after acute dosing.

Discovery of novel, potent γ-secretase inhibitors

249th National Meeting (2015)

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