Synthesis and Biological Activities of (4-Arylpiperazinyl)piperidines as Nonpeptide BACE 1 Inhibitors

E-mail: heejong@krict.re.krReceived December 28, 2010, Accepted February 14, 2011Inhibition of BACE 1 activity is considered as a promising therapeutic target for Alzheimer’s Disease (AD).Synthesis and inhibitory activities of (4-arylpiperazinyl)piperidines by bioisosteric replacement of a biarylgroup with an arylpiperazine as BACE 1 inhibitors are described. The resulting (4-arylpiperazinyl)piperidinesrepresent novel nonpeptide BACE 1 inhibitors with improved in vitro potency.Key Words : Alzheimer’s Disease (AD), BACE 1 (β-secretase), Non-peptidomimetic inhibitors, Arylpiper-azinylpiperidinesIntroductionAlzheimer’s disease (AD) is the most common form ofdementia with clinical symptoms of memory loss andimpairment on daily living activity.