LAUSR

The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor-induced angiogenesis. Inhibition of the VEGF signaling pathway has emerged as one of the most promising new approaches for cancer therapy. A series of 6,7-dimethoxy-quinazolin-4-yl-amino-nicotinamides were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity, and compound was found to be a potent inhibitor of VEGFR-2 in an homogeneous time-resolved fluorescence enzymatic assay with an IC50 as low as 48 nM (comparable activity to ZD-6474).