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

被引：36

作者：

Sun, Ying ^{[1
]}

Shan, Yuanyuan ^{[2
]}

Li, Chuansheng ^{[1
]}

Si, Ru ^{[1
]}

Pan, Xiaoyan ^{[1
]}

Wang, Binghe ^{[3
,4
]}

Zhang, Jie ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Pharm, Xian 710061, Shaanxi, Peoples R China

[3] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA

[4] Georgia State Univ, Ctr Diagnost & Therapeut, Atlanta, GA 30303 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 141卷

基金：

中国国家自然科学基金;

关键词：

Anti-angiogenesis agents; Multi-target; RTK inhibitors; Hinge-binding group; 1H-indazol-3-amine; TYROSINE KINASE INHIBITORS; HINGE-BINDING FRAGMENTS; BIOLOGICAL EVALUATION; DESIGN; DERIVATIVES; EXPLORATION; 3D-QSAR; GROWTH; UREAS; ACID;

D O I：

10.1016/j.ejmech.2017.10.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：373 / 385

页数：13

共 26 条

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