Part 2. Notch-sparing γ-secretase inhibitors: The study of novel γ-amino naphthyl alcohols.

One therapeutic approach for Alzheimer’s disease is to inhibit the cleavage of the amyloid precursor protein (APP) by γ-secretase. At the beginning of a series of studies from our laboratories, a series of novel γ-amino alcohols (1) were found to possess γ-secretase inhibitory activity and Notch-sparing effects. A new one-pot synthesis of γ-amino alcohols and the structure–activity relationship (SAR) of these analogs will be discussed.