Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor.
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.
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf@pitt.edu.
Joseph M
JM
Salamoun
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA. lazo@virginia.edu ers7g@virginia.edu.
Kelley E
KE
McQueeney
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf@pitt.edu.
Kalyani
K
Patil
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf@pitt.edu.
Steven J
SJ
Geib
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA. lazo@virginia.edu ers7g@virginia.edu.
Elizabeth R
ER
Sharlow
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA. lazo@virginia.edu ers7g@virginia.edu.
John S
JS
Lazo
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf@pitt.edu.
Peter
P
Wipf
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010100:Oxygen / Q000737:chemistry*; D055668:Photochemical Processes; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011728:Pyridones; D017027:Protein Tyrosine Phosphatases; D010100:Oxygen