13-(chloromethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one | 1041859-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 13-(chloromethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
• 英文别名: 14-chloromethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one；10-(Chloromethyl)-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaen-14-one
• CAS: 1041859-87-3
• 化学式: C₂₀H₁₃ClN₂O
• 分子量: 332.789
• InChiKey: OHQNJUHMUKUMPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  13-(chloromethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one 在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 反应 19.0h， 以71%的产率得到14-azidomethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
  参考文献：
  名称：

  [EN] OXOBENZINDOLIZINOQUINOLINES AND USES THEREOF
  [FR] OXOBENZINDOLIZINOQUINOLÉINES ET LEURS UTILISATIONS

  摘要：

  描述了芳香烯合成，取代的12H-5，11a-二氮杂二苯并[b，h]芴-11-酮。描述了利用这些细胞毒性化合物和含有它们的药物组合物治疗癌症的方法。描述了合成这种体系的两种新方法和一系列14-取代芳香烯作为新型细胞毒性、拓扑异构酶I毒素。

  公开号：

  WO2009140467A1
• 作为产物：
  描述：

  3-羟基异苯并呋喃-1(3H)-酮 在 iron(III) chloride 、 重铬酸吡啶 、 氯化亚砜 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 68.67h， 生成 13-(chloromethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
  参考文献：
  名称：

  [EN] OXOBENZINDOLIZINOQUINOLINES AND USES THEREOF
  [FR] OXOBENZINDOLIZINOQUINOLÉINES ET LEURS UTILISATIONS

  摘要：

  描述了芳香烯合成，取代的12H-5，11a-二氮杂二苯并[b，h]芴-11-酮。描述了利用这些细胞毒性化合物和含有它们的药物组合物治疗癌症的方法。描述了合成这种体系的两种新方法和一系列14-取代芳香烯作为新型细胞毒性、拓扑异构酶I毒素。

  公开号：

  WO2009140467A1

文献信息

• Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure–activity relationships
  作者：Maris A. Cinelli、Brenda Cordero、Thomas S. Dexheimer、Yves Pommier、Mark Cushman

  DOI：10.1016/j.bmc.2009.08.066

  日期：2009.10

  The aromathecin topoisomerase I (top1) inhibitors offer promising scaffolds for the development of novel cancer chemotherapeutics. They are 'composites' of the camptothecin and indenoisoquinoline top1 inhibitors. Interestingly, some structure-activity relationship (SAR) overlap between the aromathecins and the indenoisoquinolines has been observed. For both classes, placement of certain polar groups in similar regions of the heteroaromatic system improves top1 inhibitory and antiproliferative activities. A series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths has been prepared. These compounds all possess similar antiproliferative potency, but a general trend is observed: aromathecins with longer diaminoalkane substituents (>6 carbons) possess lower anti-top1 activity than their smaller counterparts (2-4 carbons), presumably as a result of unfavorable hydrophobic interactions. This trend is also noted with the indenoisoquinolines, revealing additional SAR overlap that supports the hypothesis that there is a 'universal' top1 inhibitor SAR. (C) 2009 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Evaluation of 14-Substituted Aromathecins as Topoisomerase I Inhibitors
  作者：Maris A. Cinelli、Andrew Morrell、Thomas S. Dexheimer、Evan S. Scher、Yves Pommier、Mark Cushman

  DOI：10.1021/jm800259e

  日期：2008.8.1

  The aromathecin or "rosettacin", class of topoisomerase I (top1) inhibitors is effectively a "composite" of the natural products camptothecin and luotonin A and the synthetic indenoisoquinolines. The aromathecins have aroused considerable interest following the isolation and total synthesis of 22-hydroxyacuminatine, a rare cytotoxic natural product containing the 12H-5,11a-diazadibenzo[b,h]fluoren-11-one system. We have developed two novel syntheses of this system and prepared a series of 14-substituted aromathecins as novel anti proliferative topoisomerase I poisons. These inhibitors are proposed to act via an intercalation and "poisoning" mechanism identical to camptothecin and the indenoisoquinolines. Many of these compounds possess greater antiproliferative activity and anti-top1 activity than the parent unsubstituted compound (rosettacin) and previously synthesized aromathecins, as well as greater top1 inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding solubility and localization to the DNA-enzyme complex, nitrogenous substituents located at the 14-position of the aromathecin system have been proposed to project into the major groove of the top1-DNA complex and hydrogen-bond to major-groove amino acids, thereby stabilizing the ternary complex.
• [EN] OXOBENZINDOLIZINOQUINOLINES AND USES THEREOF<br/>[FR] OXOBENZINDOLIZINOQUINOLÉINES ET LEURS UTILISATIONS
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2009140467A1

  公开（公告）日：2009-11-19

  The synthesis of aromathecins, substituted 12H-5,l la-diazadibenzo[b,h]fluoren- 11 -ones is described. Use of these cytotoxic compounds and pharmaceutical compositions containing them for the treatment of cancer is described. Two novel processes for the synthesis of this system and a series of 14-substituted aromathecins as novel cytotoxic, topoisomerase I poisons are described.

  描述了芳香烯合成，取代的12H-5，11a-二氮杂二苯并[b，h]芴-11-酮。描述了利用这些细胞毒性化合物和含有它们的药物组合物治疗癌症的方法。描述了合成这种体系的两种新方法和一系列14-取代芳香烯作为新型细胞毒性、拓扑异构酶I毒素。