Design and synthesis of BACE1 inhibitors containing a novel norstatine derivative (2 R,3 R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid

Abstract

A novel norstatine derivative, phenylthionorstatine [(2 R,3 R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; Ptns], containing a hydroxymethylcarbonyl (HMC) isostere was designed, synthesized, and stereochemically determined. Then, Ptns was introduced into the structure of BACE1 inhibitors at the P 1 position. Finally, Ptns was found as a suitable P 1 moiety for potent BACE1 inhibitor design.