2,2-dimethoxy-N-<(3',4',5'-trimethoxyphenyl)methylene>ethylamine | 39964-85-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,2-dimethoxy-N-<(3',4',5'-trimethoxyphenyl)methylene>ethylamine
• 英文别名: (3,4,5-trimethoxybenzylidene)-(2,2-dimethoxyethyl)amine；N-(2,2-dimethoxyethyl)-1-(3,4,5-trimethoxyphenyl)methanimine
• CAS: 39964-85-7
• 化学式: C₁₄H₂₁NO₅
• 分子量: 283.324
• InChiKey: RXWBBUREVBDUPM-UHFFFAOYSA-N

物化性质

• 沸点：
  >180 °C(Press: 0.4 Torr)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,2-dimethoxy-N-<(3',4',5'-trimethoxyphenyl)methylene>ethylamine 在 platinum(IV) oxide 吡啶 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 102.08h， 生成 ethyl 5,6,7-trimethoxyisoquinoline-8-carboxylate
  参考文献：
  名称：

  Banwell, Martin G.; Bonadio, Anna; Turner, Kathleen A., Australian Journal of Chemistry, 1993, vol. 46, # 3, p. 325 - 351

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 、 氨基乙醛缩二甲醇 在 magnesium sulfate 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以100%的产率得到2,2-dimethoxy-N-<(3',4',5'-trimethoxyphenyl)methylene>ethylamine
  参考文献：
  名称：

  Synthesis of Indenoisoquinoliniums and Methods of Use

  摘要：

  描述了取代的茚喹啉化合物，以及取代的茚喹啉化合物的制药配方。还描述了制备取代的茚喹啉化合物的方法。还描述了使用所述的取代的茚喹啉化合物或其制药配方来治疗哺乳动物癌症的方法。

  公开号：

  US20080242692A1

文献信息

• Synthesis of indenoisoquinoliniums and methods of use
  申请人：Purdue Research Foundation

  公开号：US07781445B2

  公开（公告）日：2010-08-24

  Substituted indenoisoquinolinium compounds, and pharmaceutical formulations of substituted indenoisoquinolinium compounds are described. Also described are processes for preparing substituted indenoisoquinolinium compounds. Also described are methods for treating cancer in mammals using the described substituted indenoisoquinolinium compounds or pharmaceutical formulations thereof.

  本文介绍了替代的吲哚异喹啉化合物以及替代的吲哚异喹啉化合物的药物配方。还介绍了制备替代吲哚异喹啉化合物的方法。同时，本文还介绍了使用所述的替代吲哚异喹啉化合物或其药物配方治疗哺乳动物癌症的方法。
• Synthesis and Mechanism of Action Studies of a Series of Norindenoisoquinoline Topoisomerase I Poisons Reveal an Inhibitor with a Flipped Orientation in the Ternary DNA−Enzyme−Inhibitor Complex As Determined by X-ray Crystallographic Analysis
  作者：Alexandra Ioanoviciu、Smitha Antony、Yves Pommier、Bart L. Staker、Lance Stewart、Mark Cushman

  DOI：10.1021/jm050076b

  日期：2005.7.1

  Several norindenoisoquinolines substituted with methoxy or methylenedioxy groups have been prepared and their anticancer properties evaluated in cancer cell cultures and in topoisomerase I inhibition assays. 2,3-Dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride (14) is a strong topoisomerase I inhibitor and also displays very high cytotoxicity in the NCI cancer cell culture screen (mean graph midpoint of 50 nM). The X-ray crystal structure of norindenoisoquinoline 14 in complex with topoisomerase I and DNA has been solved, providing insight into the structure-activity relationships within this class of new anticancer agents. The number and position of the norindenoisoquinoline substituents have a significant influence on biological activity and demonstrate that substitution on the nitrogen atom is not an absolute requirement for the antitumor effect of the indenoisoquinolines. Removal of the 11-keto group from the lead compound 1 and replacement of the N-alkyllactam with an unsubstituted pyridine ring causes the indenoisoquinoline ring system to flip over in the DNA-enzyme-inhibitor ternary complex. This allows the nitrogen atom to assume the hydrogen bond acceptor role of the 11-keto group, resulting in hydrogen bonding to Arg364.