2,3-methylenedioxy-8,9-dimethoxy-5-[2-[[tris(hydroxymethyl)methyl]amino]ethyl]dibenzo[c,h][1,6]naphthyridin-6-one | 1043867-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2,3-methylenedioxy-8,9-dimethoxy-5-[2-[[tris(hydroxymethyl)methyl]amino]ethyl]dibenzo[c,h][1,6]naphthyridin-6-one
• 英文别名: 21-[2-[[1,3-Dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]ethyl]-16,17-dimethoxy-5,7-dioxa-11,21-diazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(13),2,4(8),9,11,14,16,18-octaen-20-one
• CAS: 1043867-87-3
• 化学式: C₂₅H₂₇N₃O₈
• 分子量: 497.505
• InChiKey: ZHQXCIQTXSVKQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,3-methylenedioxy-8,9-dimethoxy-5-[2-(N,N,N-trimethylammonium)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one iodide 、 三羟甲基氨基甲烷 以 二甲基亚砜 为溶剂， 反应 2.0h， 以25%的产率得到2,3-methylenedioxy-8,9-dimethoxy-5-[2-[[tris(hydroxymethyl)methyl]amino]ethyl]dibenzo[c,h][1,6]naphthyridin-6-one
  参考文献：
  名称：

  Novel topoisomerase I-targeting antitumor agents synthesized from the N,N,N-trimethylammonium derivative of ARC-111, 5H-2,3-dimethoxy-8,9-methylenedioxy-5-[(2-N,N,N-trimethylammonium)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one iodide

  摘要：

  Several new TOP1-targeting agents were prepared using as an intermediate the N,N,N-trimethyl quaternary ammonium salt 2 of ARC-111. Direct displacement of the quaternary ammonium group with hydroxide, cyclopropylamine, imidazole, 1H-1,2,3-triazole, alkylethylenediamines, ethanolamine, and polyhydroxylated alkylamines provides a convenient means for furthering insight into the structure-activity relationships within this series of non-camptothecin TOP1-targeting agents. The relative TOP1-targeting activities and cytotoxicities were evaluated in RPMI8402 and P388 cells and their camptothecin-resistant variants. Their potential to serve as substrates for the efflux transporters MDR1 and BCRP, which are associated with multidrug resistance, was also assessed. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.02.004

文献信息

• Facile formation of hydrophilic derivatives of 5H-8,9-dimethoxy-5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one (ARC-111) and its 12-aza analog via quaternary ammonium intermediates
  作者：Wei Feng、Mavurapu Satyanarayana、Yuan-chin Tsai、Angela A. Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.bmcl.2008.05.005

  日期：2008.6

  Several new TOP1-targeting agents were prepared using as intermediates the N,N,N-trimethyl quaternary ammonium salts of either ARC-111 or its 12-aza analog (ARC-31), 3 and 4, respectively. Direct displacement of the quaternary ammonium group with water, imidazole, alkylethylenediamines, or polyhydroxylated alkylamines provides a convenient means for furthering the structure-activity relationships associated

  分别使用ARC-111或其12-氮杂类似物（ARC-31），3和4的N，N，N-三甲基季铵盐作为中间体制备了几种新的TOP1靶向剂。用水，咪唑，烷基乙二胺或多羟基化烷基胺直接取代季铵基团，为进一步促进与这些非喜树碱TOP1靶向剂相关的结构活性关系提供了便利的手段。
• Novel topoisomerase I-targeting antitumor agents synthesized from the N,N,N-trimethylammonium derivative of ARC-111, 5H-2,3-dimethoxy-8,9-methylenedioxy-5-[(2-N,N,N-trimethylammonium)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one iodide
  作者：Wei Feng、Mavurapu Satyanarayana、Yuan-Chin Tsai、Angela A. Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.ejmech.2009.02.004

  日期：2009.9

  Several new TOP1-targeting agents were prepared using as an intermediate the N,N,N-trimethyl quaternary ammonium salt 2 of ARC-111. Direct displacement of the quaternary ammonium group with hydroxide, cyclopropylamine, imidazole, 1H-1,2,3-triazole, alkylethylenediamines, ethanolamine, and polyhydroxylated alkylamines provides a convenient means for furthering insight into the structure-activity relationships within this series of non-camptothecin TOP1-targeting agents. The relative TOP1-targeting activities and cytotoxicities were evaluated in RPMI8402 and P388 cells and their camptothecin-resistant variants. Their potential to serve as substrates for the efflux transporters MDR1 and BCRP, which are associated with multidrug resistance, was also assessed. (C) 2009 Elsevier Masson SAS. All rights reserved.