N²-(6,7-methylenedioxycinnolin-4-yl)-N¹,N¹-dimethylpropane-1,2-diamine | 500214-43-7

• 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: N²-(6,7-methylenedioxycinnolin-4-yl)-N¹,N¹-dimethylpropane-1,2-diamine
• 英文别名: 2-N-([1,3]dioxolo[4,5-g]cinnolin-4-yl)-1-N,1-N-dimethylpropane-1,2-diamine
• CAS: 500214-43-7
• 化学式: C₁₄H₁₈N₄O₂
• 分子量: 274.323
• InChiKey: SWSDBZVYPBEDIY-UHFFFAOYSA-N

物化性质

• 沸点：
  363.6±34.0 °C(predicted)
• 密度：
  1.280±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N²-(6,7-methylenedioxycinnolin-4-yl)-N¹,N¹-dimethylpropane-1,2-diamine 在 palladium diacetate 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 18.0h， 生成 2,3-dimethoxy-8,9-methylenedioxy-11-[(2-dimethylamino)-1-methylethyl]-11H-5,6,11-triaza-chrysen-12-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：

  2'-氨基-4',5'-亚甲二氧基苯乙酮 在 盐酸 、 五氯化磷 、 sodium nitrite 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 9.0h， 生成 N²-(6,7-methylenedioxycinnolin-4-yl)-N¹,N¹-dimethylpropane-1,2-diamine
  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

文献信息

• Diaza- and triazachrysenes: potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435
  作者：Alexander L. Ruchelman、Sudhir K. Singh、Xiaohua Wu、Abhijit Ray、Jin-Ming Yang、Tsai-Kun Li、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/s0960-894x(02)00737-0

  日期：2002.11

  Several 5,12-diazachrysen-6-ones and 5,6,11-triazachrysen-12-ones were synthesized with varied substituents at the 5- or 11-position, respectively. Each compound was evaluated for its potential to stabilize the cleavable complex formed with TOP I and DNA. Two analogues with very potent TOP1-targeting activity, 3a and 4a, exhibited cytotoxic activity with IC50 values at or below 2 nM against RPM18402. Compound 3a was active in vivo by either ip or po administration in the human tumor xenograft athymic nude mice model. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 11H-Isoquino[4,3-c]cinnolin-12-ones novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity
  作者：A Ruchelman

  DOI：10.1016/j.bmc.2003.10.061

  日期：2004.2.15

  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.