Azaindazole ureas as potent VEGFR/PDGFR multitargeted receptor tyrosine kinase inhibitors

MEDI 360

Yujia Dai, yujia.dai@abbott.com, Kresna Hartandi, Daniel H. Albert, Jennifer J. Bouska, Gail T. Bukofzer, Cherrie K. Donawho, Keith B. Glaser, Jun Guo, Junling Li, Patrick A. Marcotte, Amanda M. Olson, Donald J. Osterling, Lori J. Pease, Niru B. Soni, Kent D. Stewart, Paul Tapang, David R. Reuter, Steven K. Davidsen, and Michael R. Michaelides. Global Pharmaceutical Research & Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064
The vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor (PDGFR) tyrosine kinases, and in particular KDR, are thought to play a prominent role in tumor angiogenesis, a process required for tumor growth and metastasis. Inhibition of VEGFR/PDGFR activation has become a compelling approach in the development of anticancer agents. In our continued efforts to identify potent and novel kinase inhibitors, we have discovered a series of azaindazole ureas that potently inhibit KDR and other VEGFR/PDGFR tyrosine kinases. These compounds also inhibit cellular KDR phosphorylation and demonstrate oral activity in an estradiol-induced mouse uterine edema model. This poster presentation will describe the synthesis, structure-activity relationships (SARs) and characterization of this series of multit-argeted kinase inhibitors.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007