bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino}ethane

• 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: bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino}ethane
• 英文别名: 6-[2-[2-[2-(5,11-Dioxoindeno[1,2-c]isoquinolin-6-yl)ethylamino]ethylamino]ethyl]indeno[1,2-c]isoquinoline-5,11-dione
• 化学式: C₃₈H₃₀N₄O₄
• 分子量: 606.681
• InChiKey: MBNDJVQCBVNJLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino}ethane 、 三氟乙酸 反应 0.5h， 以83%的产率得到bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino}ethane bis(trifluoroacetate)
  参考文献：
  名称：

  WO2007/59008

  摘要：

  公开号：
• 作为产物：
  描述：

  苯并[d]茚并[1,2-b]吡喃-5,11-二酮 、 三乙烯四胺 以 氯仿 为溶剂， 反应 48.0h， 以69%的产率得到bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino}ethane
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Bisindenoisoquinolines as Topoisomerase I Inhibitors

  摘要：

  The indenoisoquinolines represent a class of non-camptothecin topoisomerase I (Top1) inhibitors that exert cytotoxicity by trapping the covalent complex formed between DNA and Top1 during relaxation of DNA supercoils. As an ongoing evaluation of Top1 inhibition and anticancer activity, indenoisoquinolines were linked via their lactam side chains to provide polyamines end-capped with intercalating motifs. The resulting bisindenoisoquinolines were evaluated for cytotoxicity in the National Cancer Institute's human cancer cell screen and for Top1 inhibition. Preliminary findings suggested that the 2-3-2and 3-3-3 linkers, referring to the number of carbons between nitrogen atoms, were optimal for both potent Top1 inhibition and cytotoxicity. Using optimized linkers, bisindenoisoquinolines were synthesized with nitro and methoxy substituents on the aromatic rings. The biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinolines and bisindenoisoquinolines as Top1 inhibitors, but cytotoxicity was maintained for both series of compounds.

  DOI：

  10.1021/jm060046o

文献信息

• WO2007/59008
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and Biological Evaluation of Bisindenoisoquinolines as Topoisomerase I Inhibitors
  作者：Muthukaman Nagarajan、Andrew Morrell、Smitha Antony、Glenda Kohlhagen、Keli Agama、Yves Pommier、Patricia A. Ragazzon、Nichola C. Garbett、Jonathan B. Chaires、Melinda Hollingshead、Mark Cushman

  DOI：10.1021/jm060046o

  日期：2006.8.1

  The indenoisoquinolines represent a class of non-camptothecin topoisomerase I (Top1) inhibitors that exert cytotoxicity by trapping the covalent complex formed between DNA and Top1 during relaxation of DNA supercoils. As an ongoing evaluation of Top1 inhibition and anticancer activity, indenoisoquinolines were linked via their lactam side chains to provide polyamines end-capped with intercalating motifs. The resulting bisindenoisoquinolines were evaluated for cytotoxicity in the National Cancer Institute's human cancer cell screen and for Top1 inhibition. Preliminary findings suggested that the 2-3-2and 3-3-3 linkers, referring to the number of carbons between nitrogen atoms, were optimal for both potent Top1 inhibition and cytotoxicity. Using optimized linkers, bisindenoisoquinolines were synthesized with nitro and methoxy substituents on the aromatic rings. The biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinolines and bisindenoisoquinolines as Top1 inhibitors, but cytotoxicity was maintained for both series of compounds.