1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1574-8. doi: 10.1016/j.bmcl.2005.12.051. Epub 2006 Jan 4.

Abstract

High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design.

Publication types

  • Comparative Study

MeSH terms

  • Binding Sites
  • Binding, Competitive
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Mimicry
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / metabolism
  • Structure-Activity Relationship
  • Sulfonic Acids / chemical synthesis
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / pharmacology*
  • Tetrahydroisoquinolines / chemistry*
  • src Homology Domains

Substances

  • Enzyme Inhibitors
  • Ligands
  • Sulfonic Acids
  • Tetrahydroisoquinolines
  • Phosphotyrosine
  • 1,2,3,4-tetrahydroisoquinoline
  • sulfamic acid
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases