Citation: Guo-Rui Gao, Meng-Yuan Li, Lin-Jiang Tong, Li-Xin Wei, Jian Ding, Hua Xie, Wen-Hu Duan. Design, synthesis and biological evaluation of O-linked indoles as VEGFR-2 kinase inhibitors (I)[J]. Chinese Chemical Letters, ;2015, 26(9): 1165-1168. doi: 10.1016/j.cclet.2015.07.016 shu

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

Guo-Rui Gao ¹ ,
Meng-Yuan Li ^2,3 ,
Lin-Jiang Tong ² ,
Li-Xin Wei ³ ,
Jian Ding ^2,, ,
Hua Xie ^2,, ,
Wen-Hu Duan ^1,4,,

1.
1 School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China;
2.
2 Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3.
3 Pharmacology and Safety Evaluation Key Laboratory of Tibetan Medicine in Qinghai Province, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China;
4.
4 Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Corresponding author: Jian Ding, Hua Xie, Wen-Hu Duan,
Received Date: 19 May 2015
Available Online: 6 July 2015
Fund Project:

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-α and β.
- VEGFR-2,
- Inhibitor,
- Indole
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