Abstract

A series of 3-styrylbenzimidamides were synthesized and biologically evaluated in a cell free FRET assay as potential BACE1 inhibitors. Some of the synthesized analogues were discovered to have moderate BACE1 inhibitory activities with IC50 values ranging from 9.3 to 295.8 μM. Molecular docking study proposed that the most potent compound (E)-2d bound to BACE1 differently in S3-S2’ subpockets forming no polar interaction with the catalytic Asp dyad compared with the 3-styrylbenzimidamides. The results would contribute to the further optimizations on benzimidamide scaffold to achieve novel small molecular BACE1 inhibitors with improved potencies.

Keywords: Alzheimer’s disease, BACE1 inhibitors, 3-styrylbenzimidamide, CADD