A three dimensional (3D) pharmacophore model of Beta-site APP cleaving enzymes 1 (BACE-1) inhibitors with strong capability of activity prediction was generated for pharmacophore-driven identification of potent multi-target neuroprotective agents. It was developed by HypoGen process in Catalyst system from a training set of 74 BACE-1 inhibitors, represented by four features: two hydrogen bond acceptors, one hydrophobic feature, and one positive ionizable feature. And the ion-dipole interactions between P-4-site of OM99-2 and residues of BACE-1 was illustrated by using Ligand Fit in Cerius 2. Subsequently, based on the similarity of 3D pharmacophore models of the BACE-1 inhibitors and the poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors, 2-aminothiazole analogues (111-115) with potent PARP-1 inhibition were predicted to be potent molecules against BACE-1. Then, the inhibitory effect on BACE-1 activity and the cytoprotective action against A beta-induced cell death of them were tested and evaluated. Among them, compound 111 proved to be a potent multi-target neuroprotective agent for the treatment of Alzheimer's disease.