3-(5-bromoindol-1-yl)propionic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(5-bromoindol-1-yl)propionic acid ethyl ester
• 英文别名: Ethyl 3-(5-bromoindol-1-yl)propanoate
• 化学式: C₁₃H₁₄BrNO₂
• mdl: MFCD11652403
• 分子量: 296.164
• InChiKey: KBOMPBKOLCLPKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(5-bromoindol-1-yl)propionic acid ethyl ester 在 氧气 、 palladium diacetate 、 溶剂黄146 、 三环己基膦 作用下， 以 甲苯 为溶剂， 反应 61.0h， 生成 3-[5-cyclopropyl-2-(2-ethylphenyl)indol-1-yl]propionic acid ethyl ester
  参考文献：
  名称：

  インドール誘導体又はその塩

  摘要：

  提供具有优异的aP2抑制作用的化合物，作为医药、aP2抑制剂、通过aP2抑制改善的疾病等治疗药物的有用性。解决方案是通过以下通用式（I）：[符号的含义请参考说明书]所示的化合物或其盐来解决上述问题。

  公开号：

  JP2015166316A
• 作为产物：
  描述：

  5-溴吲哚 、 丙烯酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以78.8%的产率得到3-(5-bromoindol-1-yl)propionic acid ethyl ester
  参考文献：
  名称：

  インドール誘導体又はその塩

  摘要：

  提供具有优异的aP2抑制作用的化合物，作为医药、aP2抑制剂、通过aP2抑制改善的疾病等治疗药物的有用性。解决方案是通过以下通用式（I）：[符号的含义请参考说明书]所示的化合物或其盐来解决上述问题。

  公开号：

  JP2015166316A

文献信息

• "MULTI-TARGET" COMPOUNDS WITH INHIBITORY ACTIVITY TOWARDS HISTONE DEACETYLASES AND TUBULIN POLYMERISATION, FOR USE IN THE TREATMENT OF CANCER
  申请人：UNIVERSITE PARIS-SUD

  公开号：US20190023645A1

  公开（公告）日：2019-01-24

  The present invention relates to the design of novel molecules, referred to as “multi-target” molecules, having a double pharmacophore and acting both as inhibitors of histone deacetylases (HDACs) and as inhibitors of tubulin polymerisation. The invention also describes the method for synthesising the “multi-target” molecules and their use in the treatment of cancer, a pharmaceutical composition comprising at least one “multi-target” molecule, and the use of such compositions in the treatment of cancer.

  本发明涉及新型分子的设计，被称为“多靶点”分子，具有双药效团，既作为组蛋白去乙酰化酶（HDACs）的抑制剂，又作为微管聚合的抑制剂。该发明还描述了合成“多靶点”分子的方法及其在癌症治疗中的应用，包括至少一种“多靶点”分子的药物组合物，以及这些组合物在癌症治疗中的应用。
• Synthesis and application of indole esters derivatives containing acrylamide group as antifouling agents
  作者：Chunhua Ni、Guobo Chen、Xia Li、Haizhou Zhao、Liangmin Yu

  DOI：10.1016/j.cplett.2021.138994

  日期：2021.10

  reference. Algal inhibiting experiment shows that indole derivatives have better algae inhibition performance. Anti-protein adsorption experiment of antifouling paints with indole derivative and chlorothalonil as antifouling agents proves that indole derivatives exhibit better protein resistance behaviors. The antifouling paints using indole derivatives as antifouling agents have excellent antifouling properties

  以5-溴-1H-吲哚为基础，通过Michael加成反应和Friedel-Crafts反应合成了两种含丙烯酰胺基的吲哚酯衍生物。合成的化合物通过1 H 核磁共振光谱 ( 1 HNMR) 和傅立叶变换红外光谱 (FTIR)进行表征。在Friedel-Crafts反应步骤中，确定了最佳工艺条件为催化剂为AlCl 3，反应时间为3天，反应温度为25℃。合成化合物的最小抑菌浓度(MIC)结果表明，两种合成化合物均比参比化合物具有更好的抗菌活性。抑藻实验表明，吲哚衍生物具有较好的抑藻性能。以吲哚衍生物和百菌清为防污剂的防污涂料的抗蛋白质吸附实验证明，吲哚衍生物表现出较好的抗蛋白质行为。使用吲哚衍生物作为防污剂的防污涂料经过24个月的海洋现场试验，具有优异的防污性能。
• “Multi-target” compounds with inhibitory activity towards histone deacetylases and tubulin polymerisation, for use in the treatment of cancer
  申请人：UNIVERSITE PARIS-SUD

  公开号：US11014871B2

  公开（公告）日：2021-05-25

  The present invention relates to the design of novel molecules, referred to as “multi-target” molecules, having a double pharmacophore and acting both as inhibitors of histone deacetylases (HDACs) and as inhibitors of tubulin polymerisation. The invention also describes the method for synthesising the “multi-target” molecules and their use in the treatment of cancer, a pharmaceutical composition comprising at least one “multi-target” molecule, and the use of such compositions in the treatment of cancer.

  本发明涉及新型分子的设计，这些分子被称为 "多靶点 "分子，具有双重药理作用，既是组蛋白去乙酰化酶（HDAC）的抑制剂，又是微管蛋白聚合的抑制剂。本发明还描述了合成 "多靶点 "分子的方法及其在癌症治疗中的应用、包含至少一种 "多靶点 "分子的药物组合物以及这种组合物在癌症治疗中的应用。
• Natural Products for Drug Discovery: Discovery of Gramines as Novel Agents against a Plant Virus
  作者：Aidang Lu、Tienan Wang、Hao Hui、Xiaoye Wei、Weihao Cui、Chunlv Zhou、Hongyan Li、Ziwen Wang、Jincheng Guo、Dejun Ma、Qingmin Wang

  DOI：10.1021/acs.jafc.8b06859

  日期：2019.2.27

  Plant viral diseases seriously affect crop yield and quality. The natural product gramine (1) and its simple structural analogues 2-35 were synthesized from indoles, amines, and aldehydes in one step. The antiviral effects of these alkaloids were evaluated systematically. Most of these compounds were found to have higher antiviral effects than commercial ribavirin for the first time. Especially compounds 22, 30, and 31 exhibited significantly higher effects than ningnanmycin, thereby emerging as novel antiviral leads for further optimization. The preliminary implementation indicated that these compounds likely inhibit the assembly of tobacco mosaic virus (TMV) by cross-linking TMV capsid protein. Gramine analogues were also found to have broad-spectrum fungicidal effects. Although gramine has been reported to have influence on germination and development of Erysiphe graminis, these compounds displayed no fungicidal effects against Blumeria graminis f. sp. tritici on wheat in our test. Some of these compounds also exhibited certain insecticidal activities.
• Design and Synthesis of Tubulin and Histone Deacetylase Inhibitor Based on <i>iso</i>-Combretastatin A-4
  作者：Diana Lamaa、Hsin-Ping Lin、Lena Zig、Cyril Bauvais、Guillaume Bollot、Jérôme Bignon、Helene Levaique、Olivier Pamlard、Joelle Dubois、Mehdi Ouaissi、Martin Souce、Athena Kasselouri、François Saller、Delphine Borgel、Chantal Jayat-Vignoles、Hazar Al-Mouhammad、Jean Feuillard、Karim Benihoud、Mouad Alami、Abdallah Hamze

  DOI：10.1021/acs.jmedchem.8b00050

  日期：2018.8.9

  Designing multitarget drugs have raised considerable interest due to their advantages in the treatment of complex diseases such as cancer. Their design constitutes a challenge in antitumor drug discovery. The present study reports a dual inhibition of tubulin polymerization and HDAC activity. On the basis of 1,1-diarylethylenes (isoCA-4) and belinostat, a series of hybrid molecules was successfully designed and synthesized. In particular compounds, 5f and 5h were proven to be potent inhibitors of both tubulin polymerization and HDAC8 leading to excellent antiproliferative activity.