Discovery of biphenyl-based VEGFR-2 inhibitors. Part 3: Design, synthesis and 3D-QSAR studies

Wen Lu; Pengfei Li; Yuanyuan Shan; Ping Su; Jinfeng Wang; Yaling Shi; Jie Zhang

doi:10.1016/j.bmc.2015.01.006

Discovery of biphenyl-based VEGFR-2 inhibitors. Part 3: Design, synthesis and 3D-QSAR studies

Wen Lu
, Pengfei Li
, Yuanyuan Shan
, Ping Su
, Jinfeng Wang
, Yaling Shi
, Jie Zhang

医学部

Xi'an Jiaotong University

科研成果: 期刊稿件 › 文章 › 同行评审

19 引用（Scopus）

摘要

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 and 20j) are potent VEGFR-2 inhibitors which are comparable to positive control. Compound 18b 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.

源语言	英语
页（从-至）	1044-1054
页数	11
期刊	Bioorganic and Medicinal Chemistry
卷	23
期	5
DOI	https://doi.org/10.1016/j.bmc.2015.01.006
出版状态	已出版 - 1 3月 2015

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10.1016/j.bmc.2015.01.006

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title = "Discovery of biphenyl-based VEGFR-2 inhibitors. Part 3: Design, synthesis and 3D-QSAR studies",

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 and 20j) are potent VEGFR-2 inhibitors which are comparable to positive control. Compound 18b 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.",

keywords = "3D-QSAR, Amide, Anticancer, Biphenyl, VEGFR-2 inhibitors",

author = "Wen Lu and Pengfei Li and Yuanyuan Shan and Ping Su and Jinfeng Wang and Yaling Shi and Jie Zhang",

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T2 - Design, synthesis and 3D-QSAR studies

AU - Lu, Wen

AU - Li, Pengfei

AU - Shan, Yuanyuan

AU - Su, Ping

AU - Wang, Jinfeng

AU - Shi, Yaling

AU - Zhang, Jie

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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 and 20j) are potent VEGFR-2 inhibitors which are comparable to positive control. Compound 18b 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.

AB - 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 and 20j) are potent VEGFR-2 inhibitors which are comparable to positive control. Compound 18b 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.

KW - 3D-QSAR

KW - Amide

KW - Anticancer

KW - Biphenyl

KW - VEGFR-2 inhibitors

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Discovery of biphenyl-based VEGFR-2 inhibitors. Part 3: Design, synthesis and 3D-QSAR studies

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