Design and synthesis of statine-Containing BACE inhibitors

Abstract Utilizing structure-based techniques and solid-phase synthesis, statine-based tetrapeptide BACE inhibitors were designed and synthesized using a heptapeptide BACE transition-state mimetic, 1 , as the starting point. Structure–activity relationship studies at the P 3 , P 2 , and P 2 ′ positions as well as the N-terminal capping group on scaffold 5 led to the discovery of potent inhibitors 27 , 32 , and 34 (IC 50 38 are discussed.