title: 2-((1H-Azol-1-yl)methyl)-N-arylbenzamides: novel dual inhibitors of VEGFR-1/2 kinases.
abstract: Novel potent derivatives of (azol-1-yl)methyl-N-arylbenzamides with improved solubility (>3mM) are described as ATP-competitive inhibitors of vascular endothelial growth factor receptor 2 (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity reaching IC(50)<100 nM in the enzymatic assay. The compounds also inhibit the related tyrosine kinase, VEGFR-1, with similar potencies. Several compounds containing bulky lipophilic substituents at the benzamide pharmacophore yielded 10- to 17-fold selectivity for the VEGFR-2 versus VEGFR-1 kinase.
authors.affiliation: Small Molecule Drug Discovery, 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: Marina
authors.initials: M
authors.lastname: Semenova
authors.forename: Victor V
authors.initials: VV
authors.lastname: Semenov
authors.forename: Evgueni
authors.initials: E
authors.lastname: Piatnitski
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D005453:Fluorescence; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000737:chemistry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D001549:Benzamides; D008055:Lipids; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2