RESUMO
Twelve 2,3-dihydro-[1,4]-dioxino[2,3-f]quinazoline derivatives were designed and evaluated as vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. The most half-maximal inhibitory concentration (IC50) values of them were less than 10â¯nM. Among these compounds, 13d displayed highly effective inhibitory activity against VEGFR-2 (IC50â¯=â¯2.4â¯nM) and excellent antiproliferative activities against human umbilical vein endothelial cells (HUVECs) (IC50â¯=â¯1.2â¯nM). When anti-tumor animal experiments were carried out in mice, the tumor almost disappeared (TGIâ¯=â¯133.0%) after six days of administration of 13d. Therefore, 13d was a potential and effective anticancer agent. The binding conformations were respectively compared between VEGFR-2 with 13d and leading compound lenvatinib, and shows that they have similar binding modes.