(6-methoxy-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone | 613679-11-1

• 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: (6-methoxy-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: BPR0L075；Methanone, (6-methoxy-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)-；(6-methoxy-1H-indol-3-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 613679-11-1
• 化学式: C₁₉H₁₉NO₅
• 分子量: 341.364
• InChiKey: UZJVBXKFBQNDTQ-UHFFFAOYSA-N

物化性质

• 熔点：
  185-187 °C(Solv: dichloromethane (75-09-2); ethyl acetate (141-78-6))
• 沸点：
  555.6±50.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  69.8
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

(6-甲氧基-1H-吲哚-3-基)-(3,4,5-三甲氧基苯基)甲酮已知的人类代谢物包括(5-羟基-6-甲氧基-1H-吲哚-3-基)-(3,4,5-三甲氧基苯基)甲酮，(4-羟基-3,5-二甲氧基苯基)-(6-甲氧基-1H-吲哚-3-基)甲酮，(7-羟基-6-甲氧基-1H-吲哚-3-基)-(3,4,5-三甲氧基苯基)甲酮，(6-羟基-1H-吲哚-3-基)-(3,4,5-三甲氧基苯基)甲酮，以及(3-羟基-4,5-二甲氧基苯基)-(6-羟基-1H-吲哚-3-基)甲酮。

(6-methoxy-1H-indol-3-yl)-(3,4,5-trimethoxyphenyl)methanone has known human metabolites that include (5-Hydroxy-6-methoxy-1H-indol-3-yl)-(3,4,5-trimethoxyphenyl)methanone, (4-Hydroxy-3,5-dimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)methanone, (7-Hydroxy-6-methoxy-1H-indol-3-yl)-(3,4,5-trimethoxyphenyl)methanone, (6-Hydroxy-1H-indol-3-yl)-(3,4,5-trimethoxyphenyl)methanone, and (3-hydroxy-4,5-dimethoxyphenyl)-(6-hydroxy-1H-indol-3-yl)methanone.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  (6-methoxy-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以95%的产率得到6-methoxy-3-(3,4,5-trimethoxy-benzyl)-1H-indole
  参考文献：
  名称：

  康布雷他汀A-4类似物，1-芳酰基吲哚和3-芳酰基吲哚的合成和构效关系的简要介绍，它们是一类新的强效抗微管蛋白药。

  摘要：

  描述了基于1-芳基吲哚和3-芳基吲哚骨架的两类新的合成抗微管蛋白化合物的结构-活性关系的合成和研究。铅化合物3、10和14对人NUGC3胃，MKN45胃，MESSA子宫，A549肺和MCF-7乳腺癌细胞系表现出有效的细胞毒性，IC50 = 0.9-26 nM。增殖的抑制与体外聚合抑制活性有关。结构活性关系表明，在氨基二苯甲酮的情况下，通过模仿甲氧基对羰基的对位取代，3-芳基吲哚的6-甲氧基取代和1-芳酰基吲哚的5-甲氧基取代在很大程度上发挥了最大活性。在吲哚环的C-2位加甲基会增加效力。3，4，5-三甲氧基苯甲酰基部分对于更好的活性是必需的，但不是必需的，并且可以被3，5-二甲氧基苯甲酰基和3，4，5-三甲氧基苄基部分取代。我们得出结论，1-和3-芳基吲哚构成了有趣的一类新的抗微管蛋白药物，具有在临床上开发用于癌症治疗的潜力。

  DOI：

  10.1021/jm049802l
• 作为产物：
  描述：

  N-(3-甲氧基苯基)苯磺酰胺 在 三氯化铝 、 三氟化硼乙醚 、 碳酸氢钠 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.75h， 生成 (6-methoxy-1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Synthesis and biological evaluation of (3,4,5-trimethoxyphenyl)indol-3-ylmethane derivatives as potential antivascular agents

  摘要：

  Combretastatin A-4 (CSA-4), a stilbene derivative, is a potent vascular disrupting agent (VDA) with the structural requirement of a cis-configuration to maintain a molecular geometry and a correct orientation of both phenyl groups. A series of indolic analogues of CSA-4 was synthesized by means of an efficient strategy. Six compounds (20b, 25b-27b, 32b, and 35b) were identified as potent inhibitors of tubulin polymerization and also displayed cytotoxic activities on B16 melanoma cells at a nanomolar level. Both activities were well correlated with the ability to induce morphological changes of EA-hy 926 endothelial cells. In conclusion, the cis-stilbene skeleton of CSA-4 could conveniently be replaced by the 3-aroylindolic moiety, thus avoiding any isomerization leading to inactive trans compounds. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.037

文献信息

• Palladium catalyzed addition of arylboronic acid or indole to nitriles: synthesis of aryl ketones
  作者：Tuluma Das、Amarnath Chakraborty、Amitabha Sarkar

  DOI：10.1016/j.tetlet.2014.11.009

  日期：2014.12

  Aryl ketones can be synthesized conveniently by a palladium catalyzed addition of arylboronic acid to nitriles in aqueous triflic acid. This catalytic system was extended to the addition of unprotected indoles to nitriles under a slightly modified condition to produce 3-acyl indoles in good yields.

  芳基酮可以通过在三氟甲磺酸水溶液中钯催化将芳基硼酸加成到腈中来方便地合成。该催化体系扩展到在稍加修饰的条件下向腈中加入未保护的吲哚，以高收率生产3-酰基吲哚。
• A General and Scalable Synthesis of Polysubstituted Indoles
  作者：David Tejedor、Raquel Diana-Rivero、Fernando García-Tellado

  DOI：10.3390/molecules25235595

  日期：——

  A consecutive 2-step synthesis of N-unprotected polysubstituted indoles bearing an electron-withdrawing group at the C-3 position from readily available nitroarenes is reported. The protocol is based on the [3,3]-sigmatropic rearrangement of N-oxyenamines generated by the DABCO-catalyzed reaction of N-arylhydroxylamines and conjugated terminal alkynes, and delivers indoles endowed with a wide array

  报道了从容易获得的硝基芳烃在 C-3 位置带有吸电子基团的 N-未保护多取代吲哚的连续 2 步合成。该协议基于由 N-芳基羟胺和共轭末端炔烃的 DABCO 催化反应产生的 N-oxyenamines 的 [3,3]-sigmatropic 重排，并提供具有多种取代模式和拓扑结构的吲哚。
• [EN] SUBSTITUTED ISOQUINOLINES AND THEIR USE AS TUBULIN POLYMERIZATION INHIBITORS<br/>[FR] ISOQUINOLÉINES SUBSTITUÉES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE POLYMÉRISATION DES TUBULINES
  申请人：EXONHIT S A

  公开号：WO2011151423A1

  公开（公告）日：2011-12-08

  The present invention relates generally to substituted isoquinolines and their use as tubulin polymerization inhibitors. In particular, the invention relates to substituted isoquinolines which possess useful therapeutic activity, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds.

  本发明总体上涉及取代异喹啉及其作为微管蛋白聚合抑制剂的应用。特别是，本发明涉及具有有用的治疗活性的取代异喹啉，这些化合物在治疗方法、药物制造以及含有这些化合物的组合物中的应用。
• [EN] S1P RECEPTORS MODULATORS<br/>[FR] MODULATEURS DES RÉCEPTEURS S1P
  申请人：AKAAL PHARMA PTY LTD

  公开号：WO2010042998A1

  公开（公告）日：2010-04-22

  The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.

  该发明涉及具有S1P受体调节活性的新化合物，最好具有对癌细胞和其他细胞类型具有凋亡活性和/或抗增殖活性。此外，该发明涉及包含该发明中至少一种化合物的药物，用于治疗由不当的S1P受体调节活性或表达引起或相关的疾病和/或病况，例如癌症。该发明的另一个方面涉及使用包含该发明中至少一种化合物的药物制备药物，用于治疗由不当的S1P受体调节活性或表达引起或相关的疾病和/或病况，如癌症。
• Decarboxylative acylation of <i>N</i>-free indoles enabled by a catalytic amount of copper catalyst and liquid-assisted grinding
  作者：Jingbo Yu、Chao Zhang、Xinjie Yang、Weike Su

  DOI：10.1039/c9ob00622b

  日期：——

  A facile decarboxylative acylation of N-free indoles with α-ketonates via liquid-assisted grinding was reported. The reaction requires only a catalytic amount of Cu(OAc)2·H2O in combination with O2 as the terminal oxidant to give various 3-acylindoles with high efficiency. Additionally, this new methodology was applicable to a gram-scale synthesis.

  报道了通过液体辅助研磨将无氮吲哚与α-酮类化合物容易地脱羧酰化。该反应仅需要催化量的Cu（OAc）2 ·H 2 O与作为末端氧化剂的O 2结合就可以高效地得到各种3-酰基环。此外，这种新方法适用于克级合成。