Design, synthesis and SAR of potent statine-based BACE-1 inhibitors: Exploration of P1 phenoxy and benzyloxy residues

Abstract

Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modification introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors.