Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation targeting angiogenetic kinases

Bioorg Med Chem Lett. 2007 Jan 1;17(1):250-4. doi: 10.1016/j.bmcl.2006.09.050. Epub 2006 Oct 5.

Abstract

A novel class of 3,7-diphenyl-4-amino-thieno and furo[3,2-c]pyridine has been designed based on pharmacophore models of ATP competitive kinase inhibitors. Versatile synthetic methods via double Suzuki coupling to explore SAR have been established and potent inhibitors against angiogenetic targets, VEGFR2, Tie-2, and EphB4, have been successfully discovered.

MeSH terms

  • 3T3 Cells
  • Adenosine Triphosphate / chemistry
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry*
  • Animals
  • Binding, Competitive
  • Drug Design
  • Furans / chemical synthesis
  • Furans / chemistry*
  • Mice
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Receptor, EphB4 / antagonists & inhibitors
  • Receptor, TIE-2 / antagonists & inhibitors
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Furans
  • Protein Kinase Inhibitors
  • Pyridines
  • Thiophenes
  • Adenosine Triphosphate
  • Receptor, EphB4
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-2