Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor

Org Biomol Chem. 2016 Jul 6;14(27):6398-402. doi: 10.1039/c6ob00946h.

Abstract

The phosphatase PTP4A3 is an attractive anticancer target, but knowledge of its exact role in cells remains incomplete. A potent, structurally novel inhibitor of the PTP4A family was obtained by photooxygenation of a less active, electron-rich thienopyridone (1). Iminothienopyridinedione 13 displays increased solution stability and is readily obtained by two new synthetic routes that converge in the preparation of 1. The late-stage photooxygenation of 1 to give 13 in high yield highlights the potential of this reaction to modify the structure and properties of a biological lead compound and generate value for expanding the scope of an SAR investigation. Analog 13 should become a valuable tool for further exploration of the role of PTP4A3 in tumor progression.

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Oxygen / chemistry*
  • Photochemical Processes*
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Pyridones / chemistry*
  • Pyridones / pharmacology*

Substances

  • Enzyme Inhibitors
  • Pyridones
  • Protein Tyrosine Phosphatases
  • Oxygen