Formylchromone derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors

Bioorg Med Chem Lett. 2003 Aug 4;13(15):2561-3. doi: 10.1016/s0960-894x(03)00479-7.

Abstract

Formylchromone inhibits a human protein tyrosine phosphatase PTP1B with a IC(50) value of 73 microM. The chemical reactivity of formylchromone was adjusted by substitution at various positions of the formylchromone skeleton. In an initial assessment of the structure-activity relationship, the most potent inhibitor showed an IC(50) of 4.3 microM against PTP1B and strong or medium selectivity against other human PTPases, LAR and TC-PTP. This compound, however, was not selective against microbial PTPases, YPTP1 and YOP. The potency and selectivity of the formylchromone derivatives expecting further improvements provides a novel pharmacophore for the design of drugs for the treatment of type 2 diabetes and obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / enzymology
  • Chromones / chemical synthesis*
  • Chromones / pharmacology*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indicators and Reagents
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Chromones
  • Enzyme Inhibitors
  • Indicators and Reagents
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases