N-[3-chloro-4-(2-morpholin-4-ylethoxy)phenyl]-3'-hydroxybiphenyl-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3-chloro-4-(2-morpholin-4-ylethoxy)phenyl]-3'-hydroxybiphenyl-3-carboxamide
• 英文别名: N-[3-chloro-4-(2-morpholin-4-ylethoxy)phenyl]-3-(3-hydroxyphenyl)benzamide
• 化学式: C₂₅H₂₅ClN₂O₄
• 分子量: 452.938
• InChiKey: MSLVOCOHTAIVGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  71
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-苄氧基溴苯 在 盐酸 、 4-二甲氨基吡啶 、 palladium on activated charcoal 、 水 、 氢气 、 碘 、 potassium carbonate 、 magnesium 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 为溶剂， 反应 52.25h， 生成 N-[3-chloro-4-(2-morpholin-4-ylethoxy)phenyl]-3'-hydroxybiphenyl-3-carboxamide
  参考文献：
  名称：

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

  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 mu M and 5.98 mu M, 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. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.006

文献信息

• Discovery of biphenyl-based VEGFR-2 inhibitors. Part 3: Design, synthesis and 3D-QSAR studies
  作者：Wen Lu、Pengfei Li、Yuanyuan Shan、Ping Su、Jinfeng Wang、Yaling Shi、Jie Zhang

  DOI：10.1016/j.bmc.2015.01.006

  日期：2015.3

  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 mu M and 5.98 mu M, 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. (C) 2015 Elsevier Ltd. All rights reserved.