Novel methyl indolinone-6-carboxylates containing an indole moiety as angiokinase inhibitors

作者:Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian*; Zhao, Yanfang*
来源:European Journal of Medicinal Chemistry, 2017, 139: 492-502.
DOI:10.1016/j.ejmech.2017.08.031

摘要

A novel series of methyl indolinone-6-carboxylates bearing an indole moiety were identified as potent angiokinase inhibitors. The most active compound, A8, potently targeted the kinase activities of vascular endothelial growth factor receptors 2 and 3, and platelet-derived growth factor receptors alpha and beta, with IC50 values in the nanomolar range. In addition, A8 effectively suppressed the proliferation of human umbilical vein endothelial cells, and HT-29 and MCF-7 cancer cells, by inducing apoptosis. Compound A8 is thus a promising candidate for further investigation.