4-chloro-[1,3]dioxolo[4,5-g]cinnoline | 500214-38-0

• 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: 4-chloro-[1,3]dioxolo[4,5-g]cinnoline
• 英文别名: 4-chloro-6,7-methylenedioxycinnoline
• CAS: 500214-38-0
• 化学式: C₉H₅ClN₂O₂
• 分子量: 208.604
• InChiKey: VPQMWSVKDUFHTK-UHFFFAOYSA-N

物化性质

• 沸点：
  253.9±40.0 °C(Predicted)
• 密度：
  1.566±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-[1,3]dioxolo[4,5-g]cinnoline 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 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
• 作为产物：
  描述：

  6,7-methylenedioxycinnolin-4(1H)-one 在 五氯化磷 三氯氧磷 作用下， 反应 1.0h， 以73%的产率得到4-chloro-[1,3]dioxolo[4,5-g]cinnoline
  参考文献：
  名称：

  [EN] METHODS FOR TREATING GASTRIC AND PANCREATIC MALIGNANCIES
  [FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS GASTRIQUES ET PANCRÉATIQUES

  摘要：

  该发明提供了治疗胰腺癌或胃癌或其转移的方法和药物组合物。

  公开号：

  WO2012015901A1
• 作为试剂：
  描述：

  6,7-methylenedioxycinnolin-4(1H)-one 、 五氯化磷 、 三氯氧磷 、 在 sodium acetate 、 乙醇 、 4-chloro-[1,3]dioxolo[4,5-g]cinnoline 作用下， 反应 1.0h， 以to give 800 mg of 4-chloro-6,7-methylenedioxycinnoline, compound 2的产率得到4-chloro-[1,3]dioxolo[4,5-g]cinnoline
  参考文献：
  名称：

  SOLUBILIZED TOPOISOMERASE POISONS

  摘要：

  该发明提供了公式I的化合物：其中A、B、W、Y、Z和R1具有规范中定义的任何含义，以及它们的药学上可接受的盐。该发明还提供了包括公式I化合物的药物组合物、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。

  公开号：

  US20090239871A1

文献信息

• [EN] METHODS FOR TREATING GASTRIC AND PANCREATIC MALIGNANCIES<br/>[FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS GASTRIQUES ET PANCRÉATIQUES
  申请人：GENZYME CORP

  公开号：WO2012015901A1

  公开（公告）日：2012-02-02

  The invention provides methods and pharmaceutical compositions for treating pancreatic cancer or gastric cancer or a metastasis thereof.

  该发明提供了治疗胰腺癌或胃癌或其转移的方法和药物组合物。
• Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)
  作者：Mavurapu Satyanarayana、Wei Feng、Liang Cheng、Angela A. Liu、Yuan-Chin Tsai、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.bmc.2008.06.046

  日期：2008.8

  Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting

  几个在乙基取代基上具有不同功能的11-乙基-2,3-二甲氧基-8,9-亚甲基二氧基-11H-异喹啉[4,3-c] cinnolin-12-具有强力的拓扑异构酶I（TOP1）靶向活性和抗肿瘤活性。评估了11-乙基取代基的2位上的各种极性取代基（包括N-甲基胺，N-异丙基胺，羟基和羟氨基）对TOP1靶向活性和细胞毒性的影响。在具有MDA-MB-435人肿瘤异种移植物的无胸腺裸鼠中，还评估了N-甲基胺和N-异丙基胺衍生物作为抗肿瘤剂。肠胃外或口服给药时，两种化合物均具有抗肿瘤活性。
• Solubilized topoisomerase poisons
  申请人：LaVoie J. Edmond

  公开号：US20050009824A1

  公开（公告）日：2005-01-13

  The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R 1 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.

  本发明提供了I式化合物：其中A、B、W、Y、Z和R1具有规范中定义的任何含义，以及其药学上可接受的盐。本发明还提供了包含I式化合物的制药组合物，制备I式化合物的过程，用于制备I式化合物的中间体，以及使用I式化合物治疗癌症的治疗方法。
• Cytotoxic agents
  申请人：LaVoie J. Edmond

  公开号：US20050009825A1

  公开（公告）日：2005-01-13

  The invention provides compounds of the invention pharmaceutical compositions comprising a compound of the invention, processes for preparing compounds of the invention, intermediates useful for preparing compounds of the invention, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

  本发明提供了本发明的化合物、包含本发明化合物的制药组合物、制备本发明化合物的方法、制备本发明化合物有用的中间体以及治疗癌症和其他拓扑异构酶介导病症的治疗方法。
• CYTOTOXIC AGENTS
  申请人：LaVoie J. Edmond

  公开号：US20080090831A1

  公开（公告）日：2008-04-17

  The invention provides compounds of the invention pharmaceutical compositions comprising a compound of the invention, processes for preparing compounds of the invention, intermediates useful for preparing compounds of the invention, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

  该发明提供了化合物的发明，包括化合物的制药组合物，制备化合物的过程，用于制备化合物的中间体以及治疗癌症和其他拓扑异构酶介导疾病的治疗方法。