6-(4-(4-bromophenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyhexanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(4-(4-bromophenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyhexanamide
• 英文别名: 6-[4-(4-bromoanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyhexanamide
• 化学式: C₂₁H₂₃BrN₄O₄
• 分子量: 475.342
• InChiKey: BGZHWIUOIXXKJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4-二氢-7-甲氧基-4-氧代喹唑啉-6-醇乙酸酯 在 氯化亚砜 、 lithium hydroxide monohydrate 、 水 、 羟胺 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 36.0h， 生成 6-(4-(4-bromophenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyhexanamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of N-phenylquinazolin-4-amine hybrids as dual inhibitors of VEGFR-2 and HDAC

  摘要：

  A single agent that simultaneously inhibits multiple targets may offer greater therapeutic benefits in cancer than single-acting agents through interference with multiple pathways and potential synergistic action. In this work, a series of hybrids bearing N-phenylquinazolin-4-amine and hydroxamic acid moieties were designed and identified as dual VEGFR-2/HDAC inhibitors. Compound 6fd exhibited the most potent inhibitory activity against HDAC with IC50 of 2.2 nM and strong inhibitory effect against VEGFR-2 with IC50 of 74 nM. It also showed the most potent inhibitory activity against a human breast cancer cell line MCF-7 with IC50 of 0.85 mu M. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the active binding sites of VEGFR-2 and HDLP ((Histone Deacetylase-Like Protein), which demonstrates that compound 6fd is a potential agent for cancer therapy deserving further researching. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.033

文献信息

• Design, synthesis and biological evaluation of N-phenylquinazolin-4-amine hybrids as dual inhibitors of VEGFR-2 and HDAC
  作者：Fan-Wei Peng、Ji Xuan、Ting-Ting Wu、Jia-Yu Xue、Zi-Wei Ren、Da-Ke Liu、Xiu-Qi Wang、Xin-Hang Chen、Jia-Wei Zhang、Yun-Gen Xu、Lei Shi

  DOI：10.1016/j.ejmech.2015.12.033

  日期：2016.2

  A single agent that simultaneously inhibits multiple targets may offer greater therapeutic benefits in cancer than single-acting agents through interference with multiple pathways and potential synergistic action. In this work, a series of hybrids bearing N-phenylquinazolin-4-amine and hydroxamic acid moieties were designed and identified as dual VEGFR-2/HDAC inhibitors. Compound 6fd exhibited the most potent inhibitory activity against HDAC with IC50 of 2.2 nM and strong inhibitory effect against VEGFR-2 with IC50 of 74 nM. It also showed the most potent inhibitory activity against a human breast cancer cell line MCF-7 with IC50 of 0.85 mu M. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the active binding sites of VEGFR-2 and HDLP ((Histone Deacetylase-Like Protein), which demonstrates that compound 6fd is a potential agent for cancer therapy deserving further researching. (C) 2015 Elsevier Masson SAS. All rights reserved.