Potent pyrrolidine- and piperidine-based BACE-1 inhibitors

Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.

Graphical abstractThe discovery and development of novel BACE-1 inhibitors incorporating a cyclic amine scaffold is described.Figure optionsDownload full-size imageDownload as PowerPoint slide