7-Aminopyrazolo[1,5-a]pyrimidines as Potent Multitargeted Receptor

J. Med. Chem. 2008, 51, 3777–3787

3777

7-Aminopyrazolo[1,5-a]pyrimidines as Potent Multitargeted Receptor Tyrosine Kinase Inhibitors 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 Global Pharmaceutical Research and DeVelopment, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6100 ReceiVed NoVember 7, 2007

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 (