Design, synthesis and biological evaluation of O-linked indoles as VEGFR-2 kinase inhibitors (I)

被引：9
|
作者：
Gao, Guo-Rui [1 ]
Li, Meng-Yuan [2 ,3 ]
Tong, Lin-Jiang [2 ]
Wei, Li-Xin [3 ]
Ding, Jian [2 ]
Xie, Hua [2 ]
Duan, Wen-Hu [1 ,4 ]
机构：
[1] E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
[3] Chinese Acad Sci, Northwest Inst Plateau Biol, Pharmacol & Safety Evaluat Key Lab Tibetan Med Qi, Xining 810008, Peoples R China
[4] Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China
来源：
CHINESE CHEMICAL LETTERS | 2015年 / 26卷 / 09期
基金：
中国国家自然科学基金;
关键词：
VEGFR-2; Inhibitor; Indole; ENDOTHELIAL GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA; FACTOR RECEPTOR; CANCER; POTENT;
D O I：
10.1016/j.cclet.2015.07.016
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a series of O-linked indoles as potent inhibitors of VEGFR-2. Among these compounds, 18 showed significant anti-angiogenesis activities via VEGFR-2 in enzymatic proliferation assays, with IC50 value of 3.8 nmol/L. Kinase selectivity profiling revealed that 18 was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-alpha and beta. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：1165 / 1168
页数：4
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