7-Aminopyrazolo[1,5-a]pyrimidines as Potent Multitargeted Receptor Tyrosine Kinase Inhibitors.
作者
Frey, Robin R.;Curtin, Michael L.;Albert, Daniel H.;Glaser, Keith B.;Pease, Lori J.;Soni, Niru B.;Bouska, Jennifer J.;Reuter, David;Stewart, Kent D.;Marcotte, Patrick;Bukofzer, Gail;Li, Junling;Davidsen, Steven K.;Michaelides, Michael R.;
[摘要]：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 compds., such as 34a, are potent inhibitors of kinase insert domain-contg. receptor tyrosine kinase (KDR) both enzymically (<10 nM) and cellularly (<10 nM). In addn., compd. 34a possesses a favorable pharmacokinetic profile and demonstrates efficacy in the estradiol-induced murine uterine edema (UE) model (ED50 = 1.4 mg/kg).
