N-(6,7-methylenedioxycinnolin-4-yl)-N-[2-(4-methyl-1-piperazinyl)ethyl]-2-iodo-4,5-dimethoxybenzamide | 677725-68-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(6,7-methylenedioxycinnolin-4-yl)-N-[2-(4-methyl-1-piperazinyl)ethyl]-2-iodo-4,5-dimethoxybenzamide
• CAS: 677725-68-7
• 化学式: C₂₅H₂₈IN₅O₅
• 分子量: 605.432
• InChiKey: IGMJHRDUPDALKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.87
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  89.49
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-(6,7-methylenedioxycinnolin-4-yl)-N-[2-(4-methyl-1-piperazinyl)ethyl]-2-iodo-4,5-dimethoxybenzamide 在 palladium diacetate 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以23%的产率得到16,17-Dimethoxy-21-[2-(4-methylpiperazin-1-yl)ethyl]-5,7-dioxa-11,12,21-triazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(13),2,4(8),9,11,14,16,18-octaen-20-one
  参考文献：
  名称：

  11H-Isoquino[4,3-c]cinnolin-12-ones novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity

  摘要：

  Recent studies have identified 2,3-dimethoxy-8,9-methylenedioxy-11-[(2-dimethylamino)ethyl]-22H-isoquino[4,3-c]cinnolin-12-one (1a) as a novel topoisomerase 1-targeting agent with potent cytotoxic activity. The effect of varied substituents at the 11-position of 2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones on topoisomerase I-targeting activity and cytotoxicity was evaluated. Potent TOP1-targeting activity was observed when the 11-position was substituted with either a 2-(N,N-dimethylamino)ethyl, a 2-(N,N-diethylamino)ethyl, a n-butyl, or a 2-(pyrrolidin-1-yl)ethyl group. The addition of a beta-methyl group to la provided an analogue with dramatically reduced TOP1-targeting activity and cytotoxicity. Analogues of la wherein the 2(N,N-dimethylamino)ethyl group was replaced with a (2-tetrahydrofuranyl)methyl, a 2-(piperidin-1-yl)ethyl, or a 2-(4-methylpiperazin-1-yl)ethyl substituent exhibited decreased activity as TOP1-targeting agents. Replacement of the dimethoxy groups of la with hydrogen atoms resulted in an analogue with significantly decreased TOP1-targeting activity and cytotoxicity. Removal of both the vicinal dimethoxyl groups and the methylenedioxy moiety resulted in a complete loss of TOP1-targeting activity. The presence of a 9-nitro substituent in place of the 8,9-methylenedioxy group of la resulted in a decrease in relative TOP1-targeting activity and cytotoxicity. Compounds 1a and the 11-n-butyl analogue 1d were evaluated for antitumor activity in the human tumor xenograft model using athymic nude mice. The non-estrogen responsive breast tumor cell line MDA-MB-435 was used in these assays. At dose levels that approached its maximum tolerated dose, la proved to be effective in inhibiting tumor growth in vivo when administered orally or by ip injection. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.061
• 作为产物：
  描述：

  4,5-二甲氧基-2-碘苯甲酸 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-(6,7-methylenedioxycinnolin-4-yl)-N-[2-(4-methyl-1-piperazinyl)ethyl]-2-iodo-4,5-dimethoxybenzamide
  参考文献：
  名称：

  11H-Isoquino[4,3-c]cinnolin-12-ones novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity

  摘要：

  Recent studies have identified 2,3-dimethoxy-8,9-methylenedioxy-11-[(2-dimethylamino)ethyl]-22H-isoquino[4,3-c]cinnolin-12-one (1a) as a novel topoisomerase 1-targeting agent with potent cytotoxic activity. The effect of varied substituents at the 11-position of 2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones on topoisomerase I-targeting activity and cytotoxicity was evaluated. Potent TOP1-targeting activity was observed when the 11-position was substituted with either a 2-(N,N-dimethylamino)ethyl, a 2-(N,N-diethylamino)ethyl, a n-butyl, or a 2-(pyrrolidin-1-yl)ethyl group. The addition of a beta-methyl group to la provided an analogue with dramatically reduced TOP1-targeting activity and cytotoxicity. Analogues of la wherein the 2(N,N-dimethylamino)ethyl group was replaced with a (2-tetrahydrofuranyl)methyl, a 2-(piperidin-1-yl)ethyl, or a 2-(4-methylpiperazin-1-yl)ethyl substituent exhibited decreased activity as TOP1-targeting agents. Replacement of the dimethoxy groups of la with hydrogen atoms resulted in an analogue with significantly decreased TOP1-targeting activity and cytotoxicity. Removal of both the vicinal dimethoxyl groups and the methylenedioxy moiety resulted in a complete loss of TOP1-targeting activity. The presence of a 9-nitro substituent in place of the 8,9-methylenedioxy group of la resulted in a decrease in relative TOP1-targeting activity and cytotoxicity. Compounds 1a and the 11-n-butyl analogue 1d were evaluated for antitumor activity in the human tumor xenograft model using athymic nude mice. The non-estrogen responsive breast tumor cell line MDA-MB-435 was used in these assays. At dose levels that approached its maximum tolerated dose, la proved to be effective in inhibiting tumor growth in vivo when administered orally or by ip injection. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.061