Abstract
The vascular endothelial growth factor (VEGF) tyrosine kinase receptors KDR 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 KDR 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.
MeSH terms
-
Angiogenesis Inhibitors / chemical synthesis*
-
Angiogenesis Inhibitors / pharmacology*
-
Databases, Factual*
-
Humans
-
Inhibitory Concentration 50
-
Models, Molecular
-
Molecular Conformation
-
Phthalazines
-
Pyridines*
-
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
-
Structure-Activity Relationship
-
Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
-
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
-
ortho-Aminobenzoates / chemical synthesis
-
ortho-Aminobenzoates / pharmacology
Substances
-
Angiogenesis Inhibitors
-
Phthalazines
-
Pyridines
-
ortho-Aminobenzoates
-
vatalanib
-
Receptors, Vascular Endothelial Growth Factor
-
Vascular Endothelial Growth Factor Receptor-1
-
Vascular Endothelial Growth Factor Receptor-2
-
anthranilamide