title: Design and synthesis of BACE1 inhibitors containing a novel norstatine derivative (2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid.
abstract: A novel norstatine derivative, phenylthionorstatine [(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; Ptns], containing a hydroxymethylcarbonyl (HMC) isostere was designed, synthesized, and stereochemically determined. Then, Ptns was introduced into the structure of BACE1 inhibitors at the P(1) position. Finally, Ptns was found as a suitable P(1) moiety for potent BACE1 inhibitor design.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Zyta
authors.initials: Z
authors.lastname: Ziora
authors.forename: Soko
authors.initials: S
authors.lastname: Kasai
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Ayaka
authors.initials: A
authors.lastname: Nagamine
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000614:Aminocaproates / Q000737:chemistry* / Q000494:pharmacology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002087:Butyrates / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008968:Molecular Conformation; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
chemical_list: C519725:(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; D000614:Aminocaproates; D002087:Butyrates; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; C034495:3-amino-2-hydroxy-5-methylhexanoic acid; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human