2-Guanidinoquinazolines as new inhibitors of the STAT3 pathway

  • Bioorg Med Chem Lett. 2014 Nov 1;24(21):5081-5. doi: 10.1016/j.bmcl.2014.09.001.
Matthew G LaPorte  1 ,  Dimas José da Paz Lima  2 ,  Feng Zhang  2 ,  Malabika Sen  3 ,  Jennifer R Grandis  4 ,  Daniel Camarco  5 ,  Yun Hua  5 ,  Paul A Johnston  6 ,  John S Lazo  7 ,  Lynn O Resnick  2 ,  Peter Wipf  8 ,  Donna M Huryn  9
Affiliations
  • 1. University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: [email protected].
  • 2. University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 3. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 4. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15260, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 5. Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 6. University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260, USA; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 7. Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
  • 8. University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260, USA; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 9. University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: [email protected].
PMID: 25288188 DOI: 10.1016/j.bmcl.2014.09.001
Abstract

Synthesis and SAR investigation of 2-guanidinoquinazolines, initially identified in a high content screen for selective STAT3 pathway inhibitors, led to a more potent analog (11c) that demonstrated improved anti-proliferative activity against a panel of HNSCC cell lines.

Keywords
Cancer cell line screening; Guanidinoquinazolines; STAT3 pathway; Skraup synthesis; Structure–activity relationships.