Recently, we reported a novel substrate-based octapeptide BACE1 inhibitor KMI-008 containing hydroxymethylcarbonyl (HMC) isostere as a transition-state mimic. Using KMI-008 as a lead compound, a small-sized and highly potent BACE1 inhibitor KMI-370 (IC(50)=3.4 nM) was designed and synthesized.
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
