Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors

作者：Sun, Ying; Shan, Yuanyuan; Li, Chuansheng; Si, Ru; Pan, Xiaoyan; Wang, Binghe; Zhang, Jie^*

来源：European Journal of Medicinal Chemistry, 2017, 141: 373-385.

DOI：10.1016/j.ejmech.2017.10.008

• Anti-angiogenesis agents
• Multi-target
• RTK inhibitors
• Hinge-binding group
• 1H-indazol-3-amine

VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4.

• 出版日期2017-12-1
• 单位西安交通大学