8-amino-5-butyl-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one | 538366-91-5

• 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: 8-amino-5-butyl-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
• 英文别名: 17-Amino-21-butyl-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: 538366-91-5
• 化学式: C₂₁H₁₉N₃O₃
• 分子量: 361.4
• InChiKey: IIZCHNVUQBBGKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 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：
  77.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二甲氨基乙醛缩二乙醇 、 8-amino-5-butyl-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one 在 sodium cyanoborohydride 、 三氟乙酸 作用下， 以40%的产率得到5-butyl-8-(2-dimethylaminoethylamino)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2008.09.048
• 作为产物：
  描述：

  2-溴-5-硝基苯甲酸 在 palladium diacetate 、 草酰氯 、 Ra-Ni 、 一水合肼 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 80.0h， 生成 8-amino-5-butyl-2,3-methylenedioxy-5H-dibenzo[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

• 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.