N'-(6-nitrocinnolin-4-yl)-N,N-dimethylethane-1,2-diamine | 658710-31-7

• 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-nitrocinnolin-4-yl)-N,N-dimethylethane-1,2-diamine
• 英文别名: N',N'-dimethyl-N-(6-nitrocinnolin-4-yl)ethane-1,2-diamine
• CAS: 658710-31-7
• 化学式: C₁₂H₁₅N₅O₂
• 分子量: 261.283
• InChiKey: JRWNSMIRAXRQOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  86.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N'-(6-nitrocinnolin-4-yl)-N,N-dimethylethane-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 2.0h， 生成 11-(2-dimethylaminoethyl)-2,3-dimethoxy-9-nitro-11H-5,6,11-triazachrysen-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：

  6-nitro-4-phenoxy-cinnoline 、 N,N-二甲基乙二胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以72%的产率得到N'-(6-nitrocinnolin-4-yl)-N,N-dimethylethane-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

• Nitro and amino substituted topoisomerase agents
  申请人：——

  公开号：US20040102443A1

  公开（公告）日：2004-05-27

  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 and infections using compounds of formula I.

  本发明提供了公式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。本发明还提供了包括公式I化合物的制药组合物，制备公式I化合物的过程，用于制备公式I化合物的中间体，以及使用公式I化合物治疗癌症和感染的治疗方法。
• [EN] NITRO AND AMINO SUBSTITUTED DIBENZONAPHTHYRIDINES AS TOPOISOMERASE AGENTS<br/>[FR] AGENTS TOPOISOMERASE NITRO ET AMINO SUBSTITUES
  申请人：UNIV RUTGERS

  公开号：WO2004014906A3

  公开（公告）日：2004-04-29
• US6992089B2
  申请人：——

  公开号：US6992089B2

  公开（公告）日：2006-01-31
• 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.