Synthesis, in vitro Biological Evaluation and Molecular Docking Studies of Benzimidamides as Potential BACE1 Inhibitors
Yan Niu, Haifei Gao, Fengrong Xu, Chao Wang, Peng Liu, Guanyu Yang, Qi Sun, Ping Xu · Chemical Biology & Drug Design · 2012
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 IC(50) 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.