SYNTHESIS OF PHENYLTHIONORSTATINE AND ITS APPLICATION TO BACE1 INHIBITOR

DOI

Bibliographic Information

Other Title
  • フェニルチオノルスタチンの合成とBACE1阻害剤への導入

Description

We reported potent and small-sized BACE1 inhibitors containing phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] at P1 position as a transition-state mimic. We replaced the Pns by its thio-derivative. Herein, we present the synthesis of a novel phenylthionorstatine [(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; Ptns] as a P1 moiety, and then, an application to the BACE1 inhibitors design. We have synthesized Ptns starting from readily available N-benzyloxycarbonyl-serine and after multistep reaction (including Weinreb amide formation, thiophenyl group introduction, through cyanohydrin derivative the transformation into the 2-hydroxy ester and then acid). Ptns was applied to SPPS (solid phase peptide synthesis). The peptide inhibitors of BACE1 containing Pns or Ptns at the P1 position, were adopted to enzyme assay and showed high BACE1 inhibitory activity.

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Keywords

Details 詳細情報について

  • CRID
    1390001205634195968
  • NII Article ID
    130006996462
  • DOI
    10.14895/hannou.32.0.116.0
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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