Design, synthesis and biological evaluation of quinoline amide derivatives as novel VEGFR-2 inhibitors.

Research paper by Ying Y Yang, Lei L Shi, Yang Y Zhou, Huan-Qiu HQ Li, Zhen-Wei ZW Zhu, Hai-Liang HL Zhu

Indexed on: 15 Oct '10Published on: 15 Oct '10Published in: Bioorganic & Medicinal Chemistry Letters


Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in the process of cancer angiogenesis. A series of quinoline amide derivatives were prepared and found to be good inhibitors of VEGFR-2. The inhibitory activities were investigated against VEGFR-2 kinase and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 6 (5-chloro-2-hydroxy-N-(quinolin-8-yl)benzamide) exhibited the most potent inhibitory activity (IC(50)=3.8 and 5.5 nM for VEGFR-2 kinase and HUVEC, respectively). Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of VEGFR-2, which demonstrates that compound 6 is a potential agent for cancer therapy deserving further researching.