Molecular docking and structure–activity relationship studies on benzothiazole
based non-peptidic BACE-1 inhibitors

Weijun Xu, Gang Chen, Weiliang Zhu, Zhili Zuo

A similarity search on the structural analogs of an inhibitor of BACE-1 with IC50 2.8 lM, which contained
a P1 benzothiazole group together with a triazine ring linked by a secondary amine group, was described
in this Letter and some more potent inhibitors against BACE-1 were identified. The most potent compound
5 (IC50 = 0.12 lM) increases the inhibitory potency by 24 folds. Our results suggest that a pyrrolidinyl
side group at the P30 and P40 of the inhibitors are favored for strong inhibition and a small
aromatic group at the P4 position is also essential to the potency.