Identification of a new chemical class of potent angiogenesis inhibitors based on conformational considerations and database searching

The vascular endothelial growth factor (VEGF) tyrosine kinase receptors VEGFR2/KDR/Flk-1 and Flt-1 are targets of current interest in Anticancer drug research. PTK787/ZK222584 is a potent inhibitor of these enzymes in clinical evaluation as an antiangiogenic agent. The development of a hypothesis concerning the bioactive conformation of this compound has led to the discovery of a new class of potent inhibitors of VEGFR2/KDR/Flk-1 and Flt-1, the anthranilamides. This could be achieved with a limited experimental effort, which only involved the testing of one archive compound and the synthesis and testing of one appropriate analogue.