1. 7-Aminopyrazolo[1,5-a]pyrimidines as Potent Multitargeted Receptor Tyrosine Kinase Inhibitors.
- Author
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Robin R. Frey, Michael L. Curtin, Daniel H. Albert, Keith B. Glaser, Lori J. Pease, Niru B. Soni, Jennifer J. Bouska, David Reuter, Kent D. Stewart, Patrick Marcotte, Gail Bukofzer, Junling Li, Steven K. Davidsen, and Michael R. Michaelides
- Subjects
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PYRAZOLES , *PROTEIN-tyrosine kinase inhibitors , *VASCULAR endothelial growth factors , *PHARMACOKINETICS - Abstract
7-Aminopyrazolo[1,5- a]pyrimidine urea receptor tyrosine kinase inhibitors have been discovered. Investigation of structure−activity relationships of the pyrazolo[1,5- a]pyrimidine nucleus led to a series of 6-(4- N, N′-diphenyl)ureas that potently inhibited a panel of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases. Several of these compounds, such as 34a, are potent inhibitors of kinase insert domain-containing receptor tyrosine kinase (KDR) both enzymatically (<10 nM) and cellularly (<10 nM). In addition, compound 34apossesses a favorable pharmacokinetic profile and demonstrates efficacy in the estradiol-induced murine uterine edema (UE) model (ED 50= 1.4 mg/kg). [ABSTRACT FROM AUTHOR]
- Published
- 2008
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