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- Title
Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation.
- Authors
Yan, Wei; Huang, Zhaoru; Wang, Zhengyu; Cao, Sufen; Tong, Linjiang; Zhang, Tao; Wang, Chen; Zhou, Lin; Ding, Jian; Luo, Cheng; Zhou, Jinpei; Xie, Hua; Duan, Wenhu
- Abstract
In this study, we described the design, synthesis, and biological evaluation of 1,3-diaryl-pyridones as vascular endothelial growth factor receptor-2 ( VEGFR-2) inhibitors. The 1,3-diaryl-pyridones were synthesized via Chan-Lam and Suzuki coupling reactions. Two representative compounds, 17 and 35h, displayed excellent enzymatic inhibitory activities, with IC50 values of 3.5 and 3.0 n m, respectively. Furthermore, compounds 17 and 35h blocked the tube formation and suppressed the VEGF-induced phosphorylation of VEGFR-2 and downstream extracellular signal-regulated kinases (Erk) in human umbilical vein endothelial cells ( HUVECs) at 10 n m concentration. The docking simulation showed that compound 17 bound well into the active site of VEGFR-2 via two hydrogen bonds and hydrophobic interactions.
- Subjects
BIOSYNTHESIS; ENDOTHELIAL cells; ENDOTHELIAL growth factors; ENDOTHELIAL seeding; COUPLING reactions (Chemistry)
- Publication
Chemical Biology & Drug Design, 2016, Vol 87, Issue 5, p694
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12703