title: 4-(Azolylphenyl)-phthalazin-1-amines: Novel inhibitors of VEGF receptors I and II.
abstract: Novel potent derivatives of phthalazine are described as ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds display VEGFR-2 inhibitory activity reaching that of Vatalanib 3 (IC50 < 100 nm) in an HTRF enzymatic assay. Several derivatives also show good potential for the development as VEGFR-2 specific inhibitors showing 15-20-fold selectivity over VEGFR-1.
authors.affiliation: Chemical Diversity, Inc., 11558 Sorrento Valley Road, San Diego, CA 92121, USA. ask@chemdiv.com
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Victor V
authors.initials: VV
authors.lastname: Semenov
authors.forename: Daniel
authors.initials: D
authors.lastname: Milligan
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001667:Binding, Competitive; D015195:Drug Design; D006801:Humans; D010793:Phthalazines / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C404768:vatalanib; D000255:Adenosine Triphosphate; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2