14-(1,3-propanediaminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride

• 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: 14-(1,3-propanediaminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
• 英文别名: 10-[(3-Aminopropylamino)methyl]-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;hydrochloride
• 化学式: C₂₃H₂₂N₄O*3ClH
• 分子量: 479.837
• InChiKey: ARGABUZMOUJOAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  71.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-氨苯基)-2-氯乙酮 在 盐酸 、 对甲苯磺酸 作用下， 以 甲醇 、 氯仿 、 二甲基亚砜 、 苯 为溶剂， 反应 42.0h， 生成 14-(1,3-propanediaminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
  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.