LAUSR

The identification of agents with antiproliferative activity against endothelial cells has significant value for the treatment of many angiogenesis-dependent pathologies. The vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis and are major targets in cancer therapy. A series of novel 6,7-dimethoxy-quinazolin-4-yl-amino-thiophene-2-carboxamides were synthesized and evaluated as antagonists of VEGFR-1 and VEGFR-2. More specifically, several analogues exhibited low micromolar to nanomolar potency in the inhibition of VEGFR-1 and VEGFR-2. The most potent compound in this series, compound , was found to be a potent inhibitor of VEGFR-2 in a homogeneous time-resolved fluorescence enzymatic assay with an IC50 as low as 87 nm.