Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors.

Abstract

Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.

• Authors: Yujia Dai, Kresna Hartandi, Niru B Soni, Lori J Pease, David R Reuter, Amanda M Olson, Donald J Osterling, Stella Z Doktor, Daniel H Albert, Jennifer J Bouska, Keith B Glaser, Patrick A Marcotte, Kent D Stewart, Steven K Davidsen, Michael R Michaelides
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 1 Pg. 386-90 (Jan 01 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18023347 (Publication Type: Journal Article)

Chemical References

• Aminopyridines
• Protein Kinase Inhibitors
• Pyrazoles
• Urea
• Receptors, Platelet-Derived Growth Factor
• Receptors, Vascular Endothelial Growth Factor

Topics

• Administration, Oral
• Aminopyridines (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Animals
• Biological Availability
• Edema (drug therapy, metabolism)
• Female
• Inhibitory Concentration 50
• Mice
• Models, Molecular
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Pyrazoles (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Receptors, Platelet-Derived Growth Factor (antagonists & inhibitors)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Structure-Activity Relationship
• Urea (analogs & derivatives, chemical synthesis, pharmacology)
• Uterine Diseases (drug therapy, metabolism)