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

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...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2008, Vol.18 (1), p.386-390
Hauptverfasser:	Dai, Yujia, Hartandi, Kresna, Soni, Niru B., Pease, Lori J., Reuter, David R., Olson, Amanda M., Osterling, Donald J., Doktor, Stella Z., Albert, Daniel H., Bouska, Jennifer J., Glaser, Keith B., Marcotte, Patrick A., Stewart, Kent D., Davidsen, Steven K., Michaelides, Michael R.
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Aminopyridines - chemical synthesis Aminopyridines - chemistry Aminopyridines - pharmacokinetics Aminopyridines - pharmacology Animals Biological and medical sciences Biological Availability Edema - drug therapy Edema - metabolism Female Inhibitory Concentration 50 KDR Medical sciences Mice Miscellaneous Models, Molecular Pharmacology. Drug treatments Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Protein Kinase Inhibitors - pharmacology Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrazoles - pharmacokinetics Pyrazoles - pharmacology Pyrazolopyridines Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors Structure-Activity Relationship Urea - analogs & derivatives Urea - chemical synthesis Urea - pharmacology Uterine Diseases - drug therapy Uterine Diseases - metabolism VEGFR/PDGFR kinase inhibitors
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Zusammenfassung:	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. 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.
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2007.10.018