title: Synthesis and biological evaluation of benzamides and benzamidines as selective inhibitors of VEGFR tyrosine kinases.
abstract: A series of benzamidines and benzamides was synthesized as selective inhibitors of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, and tested for inhibitory activity toward autophosphorylation by the enzyme assay. Selective inhibition of VEGFR-2 tyrosine kinase was observed in the salicylic amide 4e and the anthranilic amidine 5a, and their percent inhibitions of VEGFR-2 tyrosine kinase were 44-60% at a 10 microM concentration of compounds. The salicylic amide 4a showed inhibition of both VEGFR-1 and VEGFR-2 tyrosine kinases at a 10 microM concentration.
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University, Tokyo 171-8588, Japan. hiroyuki.nakamura@gakushuin.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Masaharu
authors.initials: M
authors.lastname: Uno
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Toru
authors.initials: T
authors.lastname: Asano
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Ban
authors.forename: Hidesuke
authors.initials: H
authors.lastname: Fukazawa
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D001550:Benzamidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D001549:Benzamides; D001550:Benzamidines; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2