Discovery of biphenyl-based VEGFR-2 inhibitors. Part 3: Design, synthesis and 3D-QSAR studies. Issue 5 (1st March 2015)

• Record Type: Journal Article
• Authors: Lu, Wen; Li, Pengfei; Shan, Yuanyuan; Su, Ping; Wang, Jinfeng; Shi, Yaling; Zhang, Jie
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 5(2015)
• Page Start: 1044
• Page End: 1054
• Publication Date: 2015-03-01
• Subjects: VEGFR-2 inhibitors -- Biphenyl -- Amide -- Anticancer -- 3D-QSAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.01.006
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: These biphenyl amides have potential to be further developed as novel VEGFR-2 inhibitors and could be a promising starting point for further medicinal chemistry efforts. Abstract: VEGFR-2 plays an essential role in angiogenesis and is a central target for anticancer drug discovery. In order to develop novel VEGFR-2 inhibitors, we designed and synthesized 33 biphenyl amides based on our previously reported lead compound. The biological results indicated that four compounds (18b, 20e, 20h and20j ) are potent VEGFR-2 inhibitors which are comparable to positive control. Compound18b displayed the most potent VEGFR-2 inhibition with IC50 value of 2.02 nM. Moreover, it exhibited promising antiproliferative activity against MCF-7 and SMMC-7721 cells with IC50 values of 1.47 μM and 5.98 μM, respectively. Molecular docking and 3D-QSAR studies were also carried out. The results indicated that these biphenyl amides could serve as promising leads for further optimization as novel VEGFR-2 inhibitors.