Synthesis and biological evaluation of benzamides and benzamidines as selective inhibitors of VEGFR tyrosine kinases.
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.
Nakamura
Hiroyuki
H
Department of Chemistry, Faculty of Science, Gakushuin University, Tokyo 171-8588, Japan. hiroyuki.nakamura@gakushuin.ac.jp
Sasaki
Yusuke
Y
Uno
Masaharu
M
Yoshikawa
Tomohiro
T
Asano
Toru
T
Ban
Hyun Seung
HS
Fukazawa
Hidesuke
H
Shibuya
Masabumi
M
Uehara
Yoshimasa
Y
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
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