Design, synthesis and in vitro evaluation studies of sulfonyl-amino-acetamides as small molecule BACE-1 inhibitors.

The identification of a series of sulfonyl-amino-acetamides as BACE-1 (β-secretase) inhibitors for the treatment of Alzheimer's disease is reported. The derivatives were designed based on the docking simulation study, synthesized and assessed for BACE-1 inhibition in vitro. The designed ligands revealed desired binding interactions with the catalytic aspartate dyad and occupance of S1 and S2' active site regions. These in silico results correlated well with in vitro activity. Out of 33 compounds synthesized, 12 compounds showed significant inhibition at 10μM concentration. The most active compound 2.17S had IC50 of 7.90μM against BACE-1, which was concomitant with results of in silico docking study.