Progress toward a practical BACE-1 inhibitor.

Over the last six years, numerous research groups in both academia and industry have synthesized inhibitors of beta-amyloid cleaving enzyme-1 (BACE-1) in the hope of developing a therapy to halt or even reverse the progression of Alzheimer's disease. While several compounds have been demonstrated to be potent in vitro inhibitors of BACE-1, only a small subset of these compounds are able to satisfy other practical considerations essential for the development of a preclinical drug candidate. These considerations include selectivity of the inhibitor toward BACE-1 over other enzymes, cellular activity, and in vivo activity in an animal model. This review will summarize the recent development of BACE-1 inhibitors with particular focus placed on inhibitors that address some of the requirements necessary for a practical drug candidate.