Synthesis of triazole-linked beta-C-glycosyl dimers as inhibitors of PTP1B

Bioorg Med Chem. 2008 Nov 15;16(22):9757-63. doi: 10.1016/j.bmc.2008.09.066. Epub 2008 Sep 30.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for type 2 diabetes. We have successfully synthesized dimeric acetylated and benzoylated beta-C-d-glucosyl and beta-C-D-galactosyl 1,4-dimethoxy benzenes or naphthalenes by click chemistry. These compounds were further transformed into the corresponding beta-C-D-glycosyl-1,4-quinone derivatives by CAN oxidation. The in vitro inhibition test showed that dimeric benzoylated beta-C-D-glycosyl 1,4-dimethoxybenzenes or 1,4-benzoquinones were good inhibitors of PTP1B (IC(50): 0.62-0.88 miroM), with no significant difference between gluco and galacto derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones / chemical synthesis*
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dimerization
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Inhibitory Concentration 50
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism

Substances

  • Benzoquinones
  • Enzyme Inhibitors
  • Glycosides
  • Hypoglycemic Agents
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1