3-bromo-4,5-dimethoxybenzamide | 712294-58-1

• 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: 3-bromo-4,5-dimethoxybenzamide
• 英文别名: 3-bromo-4,5-dimethoxy-benzoic acid amide；3-Brom-4,5-dimethoxy-benzoesaeure-amid；5-Brom-3.4-dimethoxy-benzamid
• CAS: 712294-58-1
• 化学式: C₉H₁₀BrNO₃
• 分子量: 260.087
• InChiKey: VGULIFJEXBRFIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-4,5-dimethoxybenzamide 在 氢氧化钾 、 palladium on activated charcoal 、 次溴酸钾 、 乙醇 、 三氯氧磷 作用下， 生成 6,7-二甲氧基-4-甲基喹啉
  参考文献：
  名称：

  THE SEARCH FOR SUPERIOR DRUGS FOR TROPICAL DISEASES. II. SYNTHETIC STUDIES IN THE QUINOLINE AND PHENAN-THROLINE SERIES. SKRAUP AND CONRAD-LIMPACH-KNORR REACTIONS

  摘要：

  DOI：

  10.1021/jo01180a014
• 作为产物：
  描述：

  5-溴香兰素 在 甲酸 、 硫酸羟胺 、 双氧水 、 sodium formate 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 9.0h， 生成 3-bromo-4,5-dimethoxybenzamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of biphenyl urea derivatives as novel VEGFR-2 inhibitors

  摘要：

  VEGFR-2 在血管生成过程中起着关键作用，VEGFR-2 抑制剂已被广泛用于治疗癌症。我们一直在努力寻找强效的新型 VEGFR-2 抑制剂作为抗肿瘤药物，在此过程中，我们发现了一种具有联苯支架的强效先导化合物（HMQ-16）。将 HMQ-16 中的芳基氨基甲酰基重新排列并替换为脲基，产生了一系列新型 VEGFR-2 抑制剂。为了增强与 VEGFR-2 的亲和力，4′-乙酰基被转化为肟基。研究人员设计并合成了 14 种联苯脲衍生物，作为有效的 VEGFR-2 抑制剂。其中六种（T2、T5、T7、T9、T11、T14）表现出与索拉非尼相当的强效 VEGFR-2 抑制活性。化合物 T7 的 IC50 值为 1.08 nM，效力最强。酶和细胞检测结果表明，T7 有可能成为一种有价值的先导化合物，有待进一步优化。

  DOI：

  10.1039/c3md00192j

文献信息

• Design, synthesis and biological evaluation of biphenyl urea derivatives as novel VEGFR-2 inhibitors
  作者：Chen Wang、Jinyun Dong、Yanmin Zhang、Fang Wang、Hongping Gao、Pengfei Li、Sicen Wang、Jie Zhang

  DOI：10.1039/c3md00192j

  日期：——

  VEGFR-2 plays a critical role in vasculogenesis and VEGFR-2 inhibitors have been widely used in the treatment of cancer. In our continued efforts to search for potent and novel VEGFR-2 inhibitors as antitumor agents, we have identified a potent lead compound (HMQ-16) bearing a biphenyl scaffold. Rearrangement and replacement of arylcarbamoyl in HMQ-16 with a urea moiety generated a series of novel VEGFR-2 inhibitors. In order to enhance the affinity with VEGFR-2, the 4′-acetyl group was converted to an oxime group. Fourteen biphenyl urea derivatives were designed and synthesized as potent VEGFR-2 inhibitors. Six of them (T2, T5, T7, T9, T11, T14) exhibited potent VEGFR-2 inhibitory activity comparable to that of sorafenib. Compound T7 was the most potent with an IC50 value of 1.08 nM. The enzymatic and cellular assays suggested that T7 has potential as a valuable lead compound for further optimization.

  VEGFR-2 在血管生成过程中起着关键作用，VEGFR-2 抑制剂已被广泛用于治疗癌症。我们一直在努力寻找强效的新型 VEGFR-2 抑制剂作为抗肿瘤药物，在此过程中，我们发现了一种具有联苯支架的强效先导化合物（HMQ-16）。将 HMQ-16 中的芳基氨基甲酰基重新排列并替换为脲基，产生了一系列新型 VEGFR-2 抑制剂。为了增强与 VEGFR-2 的亲和力，4′-乙酰基被转化为肟基。研究人员设计并合成了 14 种联苯脲衍生物，作为有效的 VEGFR-2 抑制剂。其中六种（T2、T5、T7、T9、T11、T14）表现出与索拉非尼相当的强效 VEGFR-2 抑制活性。化合物 T7 的 IC50 值为 1.08 nM，效力最强。酶和细胞检测结果表明，T7 有可能成为一种有价值的先导化合物，有待进一步优化。
• Discovery of novel VEGFR-2 inhibitors. Part II: Biphenyl urea incorporated with salicylaldoxime
  作者：Hongping Gao、Ping Su、Yaling Shi、Xiuxiu Shen、Yanmin Zhang、Jinyun Dong、Jie Zhang

  DOI：10.1016/j.ejmech.2014.11.032

  日期：2015.1

  A series of novel VEGFR-2 inhibitors containing oxime as hinge binding fragment were described. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bond was employed to mimic the planar quinazoline. The oxime group was firstly introduced to interact with hinge region of VEGFR-2. Most of compounds tested showed moderate to high VEGFR-2 inhibitory activity. In particular, 121, 12p and 12y exhibited significant enzymatic inhibitory activity as well as potent antiproliferative activity against cancer cells. Molecular docking suggested that the salicylaldoxime formed two hydrogen bonds with hinge region. These biphenylureas could serve as promising lead compounds for developing novel anticancer agents. (C) 2014 Elsevier Masson SAS. All rights reserved.
• THE SEARCH FOR SUPERIOR DRUGS FOR TROPICAL DISEASES. II. SYNTHETIC STUDIES IN THE QUINOLINE AND PHENAN-THROLINE SERIES. SKRAUP AND CONRAD-LIMPACH-KNORR REACTIONS
  作者：FERNANDA MISANI、MARSTON TAYLOR BOGERT

  DOI：10.1021/jo01180a014

  日期：1945.7
• Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: Design, synthesis and biological evaluation
  作者：Chen Wang、Hongping Gao、Jinyun Dong、Yanmin Zhang、Ping Su、Yaling Shi、Jie Zhang

  DOI：10.1016/j.bmc.2013.11.027

  日期：2014.1

  A series of novel biphenyl urea derivates were synthesized and investigated for their potential to inhibit vascular endothelial growth factor receptor-2 (VEGFR-2). In particular, A7, B3 and B4 displayed significant enzymatic inhibitory activities, with IC50 values of 4.06, 4.55 and 5.26 nM. Compound A7 exhibited potent antiproliferative activity on several cell lines. SAR study suggested that the introduction of methyl at ortho-position of the biphenyl urea and tertiary amine moiety could improve VEGFR-2 inhibitory activity and antitumor effects. Molecular docking indicated that the urea moiety formed four hydrogen bonds with DFG residue. These biphenyl ureas could serve as promising lead compounds for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.