Synthesis,in vitro Biological Evaluation and Molecular Docking Studies of Benzimidamides as Potential BACE1 Inhibitors

A series of 3, 5‐disubstituted benzimidamides were synthesized and biologically evaluated as potential BACE1 inhibitors. Both the targeted compounds (benzimidamides) and the synthetic intermediates (benzonitriles) were tested for their BACE1 inhibitory activities in a cell‐free FRET assay. All the synthesized benzimidamides were active as BACE1 inhibitors and compound 6d showed the lowest IC₅₀ value of 3.35 μm . Molecular docking study proposed a binding mode, which would help to the further optimization on 6d to achieve more potent, BBB penetrant BACE1 inhibitors.