5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxy-8-nitrobenzo[c,h]-1,6-naphthyridin-6-one | 538366-79-9

• 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: 5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxy-8-nitrobenzo[c,h]-1,6-naphthyridin-6-one
• 英文别名: 8-nitro-2,3-methylenedioxy-5-[2-(N,N-dimethylamino)ethyl]-5H-dibenzo[c,h][1,6]naphthyridin-6-one；8-Nitro-2,3-Methylenedioxy-5-[2-(N,N-dimethylamino)ethyl]-5H-dibenzo[c,h] [1,6]naphthyridin-6-one；21-[2-(dimethylamino)ethyl]-17-nitro-5,7-dioxa-11,21-diazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(13),2,4(8),9,11,14(19),15,17-octaen-20-one
• CAS: 538366-79-9
• 化学式: C₂₁H₁₈N₄O₅
• 分子量: 406.398
• InChiKey: JTBKKEODUUGGJK-UHFFFAOYSA-N

物化性质

• 熔点：
  219-220 °C
• 沸点：
  651.3±55.0 °C(Predicted)
• 密度：
  1.441±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxy-8-nitrobenzo[c,h]-1,6-naphthyridin-6-one 在 Ra-Ni 肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以69.1%的产率得到8-amino-5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxybenzo[c,h]-1,6-naphthyridin-6-one
  参考文献：
  名称：

  [EN] NITRO AND AMINO SUBSTITUTED TOPOISOMERASE AGENTS
  [FR] AGENTS DE LA TOPOISOMERASE SUBSTITUES PAR NITRO ET AMINO

  摘要：

  该发明提供了公式（I）的化合物：其中R1-R9、W和X具有规范中定义的任何含义，以及它们的药用盐。该发明还提供了包含公式（I）化合物的药物组合物，制备公式（I）化合物的方法，用于制备公式（I）化合物的有用中间体，以及使用公式（I）化合物治疗癌症的治疗方法。

  公开号：

  WO2004014918A1
• 作为产物：
  描述：

  2-溴-5-硝基苯甲酸 在 palladium diacetate 、 草酰氯 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 5-[2-(N,N-dimethylamino)ethyl]-2,3-methylenedioxy-8-nitrobenzo[c,h]-1,6-naphthyridin-6-one
  参考文献：
  名称：

  Nitro and Amino Substitution in the D-Ring of 5-(2-Dimethylaminoethyl)- 2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-ones:  Effect on Topoisomerase-I Targeting Activity and Cytotoxicity

  摘要：

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one exhibits potent TOP1-targeting activity and pronounced antitumor activity. It was hypothesized that replacement of the two methoxyl groups with a nitro substituent would allow for retention of similar activity. In this study 8-, 9-, and 10-nitro-5H-2,3-methylenedioxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h] [1,6]naphthyridin-6-one and their amino derivatives were synthesized and assessed for their relative TOP1-targeting activity and cytotoxicity. In the case of both the 8- and 9-nitro analogues, their TOP1-targeting activity and cytotoxicity are greater than that of camptothecin and comparable to that of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one.

  DOI：

  10.1021/jm020498a

文献信息

• [EN] NITRO AND AMINO SUBSTITUTED TOPOISOMERASE AGENTS<br/>[FR] AGENTS DE LA TOPOISOMERASE SUBSTITUES PAR NITRO ET AMINO
  申请人：UNIV RUTGERS

  公开号：WO2004014918A1

  公开（公告）日：2004-02-19

  The invention provides compounds of formula (I): wherein R1-R9, W, and X 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R1-R9、W和X具有规范中定义的任何含义，以及它们的药用盐。该发明还提供了包含公式（I）化合物的药物组合物，制备公式（I）化合物的方法，用于制备公式（I）化合物的有用中间体，以及使用公式（I）化合物治疗癌症的治疗方法。
• Nitro and amino substituted topoisomerase agents
  申请人：——

  公开号：US20040110760A1

  公开（公告）日：2004-06-10

  The invention provides compounds of formula I: 1 wherein R 1 -R 9 , W, and X 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.

  本发明提供公式I的化合物：1，其中R1-R9，W和X具有规范中定义的任何含义及其药学上可接受的盐。本发明还提供包括公式I化合物的药物组合物，制备公式I化合物的方法，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。
• US6989387B2
  申请人：——

  公开号：US6989387B2

  公开（公告）日：2006-01-24
• Nitro and Amino Substitution in the D-Ring of 5-(2-Dimethylaminoethyl)- 2,3-methylenedioxy-5<i>H</i>-dibenzo[<i>c,h</i>][1,6]naphthyridin-6-ones:  Effect on Topoisomerase-I Targeting Activity and Cytotoxicity
  作者：Sudhir K. Singh、Alexander L. Ruchelman、Tsai-Kun Li、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1021/jm020498a

  日期：2003.5.1

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one exhibits potent TOP1-targeting activity and pronounced antitumor activity. It was hypothesized that replacement of the two methoxyl groups with a nitro substituent would allow for retention of similar activity. In this study 8-, 9-, and 10-nitro-5H-2,3-methylenedioxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h] [1,6]naphthyridin-6-one and their amino derivatives were synthesized and assessed for their relative TOP1-targeting activity and cytotoxicity. In the case of both the 8- and 9-nitro analogues, their TOP1-targeting activity and cytotoxicity are greater than that of camptothecin and comparable to that of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one.
• Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones
  作者：Lisa Sharma、Yuan-Chin Tsai、Angela A. Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.ejmech.2008.09.048

  日期：2009.4

  Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent. (C) 2008 Elsevier Masson SAS. All rights reserved.