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ID: ALA1136466

Journal: Bioorg Med Chem Lett

Title: KMI-008, a novel beta-secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic: design and synthesis of substrate-based octapeptides.

Authors: Shuto D, Kasai S, Kimura T, Liu P, Hidaka K, Hamada T, Shibakawa S, Hayashi Y, Hattori C, Szabo B, Ishiura S, Kiso Y.

Abstract: A novel class of substrate-based beta-secretase (BACE1) inhibitors containing a hydroxymethylcarbonyl (HMC) isostere was designed and synthesized. Phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] was an effective transition-state mimic at the P(1) position. Structure-activity relationships (SARs) of the P(3)-P(3)' positions of BACE1 inhibitors were studied.

CiteXplore: 14643307

DOI: 10.1016/j.bmcl.2003.09.053