Click to a focused library of benzyl 6-triazolo(hydroxy)benzoic glucosides: novel construction of PTP1B inhibitors on a sugar scaffold

Eur J Med Chem. 2011 Sep;46(9):4212-8. doi: 10.1016/j.ejmech.2011.06.025. Epub 2011 Jun 25.

Abstract

With an aim of developing novel protein tyrosine phosphatase (PTP) 1B inhibitors based on sugar scaffolds, a focused library of benzyl 6-triazolo(hydroxy)benzoic glucosides was efficiently constructed via the modular and selective Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddtion (click chemistry). These glycoconjugates bearing alkyl chain length-varied bridges between the sugar and (hydroxy)-benzoic moieties were identified as new PTP1B inhibitors with selectivity over T-Cell PTP (TCPTP), SH2-Containing PTP-1 (SHP-1), SHP-2 and Leukocyte Antigen-Related Tyrosine Phosphatase (LAR). Molecular docking study sequentially elaborated the plausible binding modes of the structurally diverse sugar-based inhibitors with PTP1B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoic Acid / chemistry*
  • Carbohydrates / chemistry*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glucosides / chemistry*
  • Glucosides / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Carbohydrates
  • Enzyme Inhibitors
  • Glucosides
  • Benzoic Acid
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1