2,3-methylenedioxy-8,9-dimethoxy-5-[(2-hydroxy)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one

• 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-hydroxy)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one
• 英文别名: 8,9-dimethoxy-2,3-methylenedioxy-5-[2-(hydroxy)ethyl]-5H-dibenzo[c,h]1,6-naphthyridin-6-one；8,9-dimethoxy-2,3-methylenedioxy-5-[2-(hydroxy)ethyl]-5H-dibenzo[c,h]1,6-naphthyridine-6-one；21-(2-Hydroxyethyl)-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
• 化学式: C₂₁H₁₈N₂O₆
• 分子量: 394.384
• InChiKey: YXRFKQOWTSQHMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N,N-二甲基甘氨酸 、 2,3-methylenedioxy-8,9-dimethoxy-5-[(2-hydroxy)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 以34%的产率得到2,3-methylenedioxy-8,9-dimethoxy-5-[(2-hydroxy)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one glycinate
  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
• 作为产物：
  描述：

  8-羟基[1,3]二氧代lo[4,5-g]喹啉-7-羧酸乙酯 在 palladium diacetate 、 三(邻甲基苯基)磷 咪唑 、 草酰氯 、 silver carbonate 、 溶剂黄146 、 potassium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 二苯醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 苯酚 为溶剂， 反应 80.25h， 生成 2,3-methylenedioxy-8,9-dimethoxy-5-[(2-hydroxy)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one
  参考文献：
  名称：

  [EN] METHODS FOR TREATING HEMATOLOGICAL MALIGNANCIES
  [FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES

  摘要：

  这项发明提供了治疗特定血液系统癌症的方法和药物组合物。

  公开号：

  WO2012015875A1

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。
• Solubilized topoisomerase poisons
  申请人：LaVoie J. Edmond

  公开号：US20050009824A1

  公开（公告）日：2005-01-13

  The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R 1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.

  本发明提供了I式化合物：其中A、B、W、Y、Z和R1具有规范中定义的任何含义，以及其药学上可接受的盐。本发明还提供了包含I式化合物的制药组合物，制备I式化合物的过程，用于制备I式化合物的中间体，以及使用I式化合物治疗癌症的治疗方法。
• SOLUBILIZED TOPOISOMERASE POISONS
  申请人：LaVoie Edmond J.

  公开号：US20090239871A1

  公开（公告）日：2009-09-24

  The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R 1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.

  该发明提供了公式I的化合物：其中A、B、W、Y、Z和R1具有规范中定义的任何含义，以及它们的药学上可接受的盐。该发明还提供了包括公式I化合物的药物组合物、用于制备公式I化合物的中间体以及使用公式I化合物治疗癌症的治疗方法。
• METHODS TO TREAT CANCER
  申请人：Lavoie Edmond J.

  公开号：US20120004235A1

  公开（公告）日：2012-01-05

  The invention provides methods and pharmaceutical compositions for treating certain cancers with compounds of formula (I) wherein A, B, W, Y, Z, and R 1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts and prodrugs.

  本发明提供了使用式(I)的化合物的方法和制药组合物，用于治疗某些癌症，其中A，B，W，Y，Z和R1具有规范中定义的任何含义，以及它们的药学上可接受的盐和前药。
• Topoisomerase poisons
  申请人：Rutgers, The State University

  公开号：EP2196205A1

  公开（公告）日：2010-06-16

  The invention provides compounds of formula (I) wherein A, B, W, Y, Z and R1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.

  本发明提供了式(I)化合物，其中A、B、W、Y、Z和R1具有说明书中定义的任何含义及其药学上可接受的盐类。本发明还提供了包含式 I 化合物的药物组合物、制备式 I 化合物的工艺、用于制备式 I 化合物的中间体以及使用式 I 化合物治疗癌症的方法。