Structure based design of a series of potent and selective non peptidic PTP-1B inhibitors

Bioorg Med Chem Lett. 2004 Feb 23;14(4):1043-8. doi: 10.1016/j.bmcl.2003.11.076.

Abstract

A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphatase.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Insecta
  • Mice
  • Mice, Knockout
  • Models, Molecular
  • Molecular Structure
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / chemistry*
  • Organophosphorus Compounds / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Organophosphorus Compounds
  • methylphosphonic acid
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Ptpn1 protein, mouse