13-chloro-2,3-dimethoxy-[1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridine | 138916-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 13-chloro-2,3-dimethoxy-[1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridine
• 英文别名: 13-Chloro-2,3-dimethoxy-[1,3]benzodioxolo[5,6-c]phenanthridine
• CAS: 138916-42-4
• 化学式: C₂₀H₁₄ClNO₄
• 分子量: 367.788
• InChiKey: VLSZEUVNGLNPED-UHFFFAOYSA-N

物化性质

• 沸点：
  574.6±45.0 °C(Predicted)
• 密度：
  1.435±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  13-chloro-2,3-dimethoxy-[1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridine 在 palladium on activated charcoal 氢气 作用下， 以72%的产率得到nornitidine
  参考文献：
  名称：

  Total synthesis of N-nornitidine

  摘要：

  The benzo[c]phenanthridine alkaloid, N-nornitidine has been synthesized employ

  DOI：

  10.1016/s0040-4039(00)93548-2
• 作为产物：
  描述：

  2-硝基-4，5-二甲氧基苯胺 在 platinum(IV) oxide lead(IV) acetate 、 盐酸 、 氢气 、 亚硝酸 、 potassium carbonate 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 13-chloro-2,3-dimethoxy-[1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridine
  参考文献：
  名称：

  Total synthesis of N-nornitidine

  摘要：

  The benzo[c]phenanthridine alkaloid, N-nornitidine has been synthesized employ

  DOI：

  10.1016/s0040-4039(00)93548-2

文献信息

• Discovery, Synthesis, and Evaluation of Oxynitidine Derivatives as Dual Inhibitors of DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1), and Potential Antitumor Agents
  作者：Xiao-Ru Zhang、Hao-Wen Wang、Wen-Lin Tang、Yu Zhang、Hui Yang、De-Xuan Hu、Azhar Ravji、Christophe Marchand、Evgeny Kiselev、Kwabena Ofori-Atta、Keli Agama、Yves Pommier、Lin-Kun An

  DOI：10.1021/acs.jmedchem.8b00639

  日期：2018.11.21

  repairing DNA lesions resulting from stalled topoisomerase IB (TOP1)–DNA covalent complex. Inhibiting TDP1 in conjunction with TOP1 inhibitors can boost the action of the latter. Herein, we report the discovery of the natural product oxynitidine scaffold as a novel chemotype for the development of TOP1 and TDP1 inhibitors. Three kinds of analogues, benzophenanthridinone, dihydrobenzophenanthridine, and benzophenanthridine

  酪氨酰-DNA磷酸二酯酶1（TDP1）是最近发现的一种酶修复DNA损伤的物质，它是由停滞的拓扑异构酶IB（TOP1）-DNA共价复合物引起的。与TOP1抑制剂一起抑制TDP1可以增强后者的作用。在这里，我们报告了天然产物氧亚硝胺支架的发现，作为开发TOP1和TDP1抑制剂的新型化学型。合成了三种类似物，苯并菲啶酮，二氢苯并菲啶和苯并菲啶衍生物，并评估了其对TOP1和TDP1的抑制作用和细胞毒性。类似物19a显示出高的TOP1抑制作用（+++），并诱导细胞TOP1cc的形成和DNA损伤，从而导致癌细胞在纳摩尔浓度范围内凋亡。体内研究表明19a在HCT116异种移植模型中显示出抗肿瘤效率。41a在MCF-7细胞中表现出额外的TDP1抑制作用，IC 50值为7μM，并且与喜树碱具有协同作用。这项工作将促进发现基于天然产物的TOP1和TDP1抑制剂的未来工作。
• A formal new access to the benzo[c]phenanthridine alkaloids, synthesis of nitidine and o-methyl fagaronine analogues.
  作者：Yves L. Janin、Emile Bisagni

  DOI：10.1016/s0040-4020(01)80559-7

  日期：1993.1

  reaction but omitting the acetic anhydride usually present in the reaction mixture. From these amines, through the thermal cyclization of their corresponding ethyl carbamates, a new access to the benzo[c]phenanthridin-6(5H)-ones was found. Preparation of water-soluble Nitidine and O-Methyl Fagaronine analogues bearing an alkylamino side chain on the C-6 position was achieved from these compounds.

  以前未报道的2-芳基-1-萘胺是通过使用Semmler-Wolf反应从2-芳基-1-四酮肟中以高收率获得的，但省略了通常存在于反应混合物中的乙酸酐。从这些胺中，通过它们相应的氨基甲酸乙酯的热环化反应，发现了一种新的苯并[c]菲咯啶-6（5H）-酮。由这些化合物可制备在C-6位带有烷基氨基侧链的水溶性亚硝啶和O-甲基法加罗宁类似物。
• WO2020/23700
  申请人：——

  公开号：——

  公开（公告）日：——
• OXYNITIDINE DERIVATIVES USEFUL AS INHIBITORS OF TOPOISOMERASE IB (TOP1) AND/OR TYROSYL-DNA PHOSPHODIESTERASE 1 (TDP1)
  申请人：The United States of America, as represented by The Secretary, Department of Health and Human Services

  公开号：EP3826717A2

  公开（公告）日：2021-06-02
• [EN] OXYNITIDINE DERIVATIVES USEFUL AS INHIBITORS OF TOPOISOMERASE IB (Top1) AND TYROSYL-DNA PHOSPHODIESTERASE 1 (Tdp1)<br/>[FR] DÉRIVÉS D'OXYNITIDINE UTILES COMME INHIBITEURS DE LA TOPOISOMÉRASE IB (TOP1) ET DE LA TYROSYL-ADN PHOSPHODIESTÉRASE 1 (TDP1)
  申请人：US HEALTH

  公开号：WO2020023700A2

  公开（公告）日：2020-01-30

  Compounds and pharmaceutically acceptable salts thereof of Formula I are disclosed. Certain compounds and salts of Formula I are active as Topl and / or Tdpl inhibitors. The disclosure provides pharmaceutical compositions containing a compound of Formula I as the only active agent, or optionally containing one or more additional active agents. Methods of using compounds of Formula I to treat cancer are provided in this disclosure. The disclosed compounds of Formula I may be used alone to treat cancer, but may also be used in combination with another active agent, such as a Topl inhibitor, for example, camptothecin or a camptothecin analogue.