title: Identification of a new chemical class of potent angiogenesis inhibitors based on conformational considerations and database searching.
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.
authors.affiliation: Oncology Research, Novartis Pharma AG, CH-4002 Basel, Switzerland. pascal.furet@pharma.novartis.com
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.forename: Guido
authors.initials: G
authors.lastname: Bold
authors.forename: Francesco
authors.initials: F
authors.lastname: Hofmann
authors.forename: Paul
authors.initials: P
authors.lastname: Manley
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Altmann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D016208:Databases, Factual; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D010793:Phthalazines; D011725:Pyridines; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D010793:Phthalazines; D011725:Pyridines; D062367:ortho-Aminobenzoates; C404768:vatalanib; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C000219:anthranilamide