Abstract: The pharmacophore model of γ-secretase inhibitors was established by the Catalyst software with the training set of Benzodiazepine-based γ-secretase inhibitors. Based on the action mechanism and the known structure-activity relationship, a fitting pharmacophore model (RMS=0.366343, Correl=0.95535, Weight=1.17389, Config=18.8671) including two hydrogen-bonding acceptors, an aliphatic hydrophobic core and an aromatic ring center, was confirmed. This pharmacophore model will contribute to the design and synthesis of new-type γ-secretase inhibitors.

Key words: Alzheimer′s disease, Computer-aided drug design, γ-secretase inhibitor, Pharmaophore