1,4-二氧杂-7-氮杂螺[4.4]壬烷-7-羧酸,乙基酯 | 14891-11-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 1,4-二氧杂-7-氮杂螺[4.4]壬烷-7-羧酸,乙基酯
• 英文名称: 7-Carbaethoxy-1,4-dioxa-7-azaspiro<4,4>nonan
• 英文别名: N-ethoxycarbonyl-3-pyrrolidinone ethylene ketal；1,4-dioxa-7-aza-spiro[4.4]nonane-7-carboxylic acid ethyl ester；Ethyl 1,4-dioxa-7-azaspiro[4.4]nonane-7-carboxylate；ethyl 1,4-dioxa-7-azaspiro[4.4]nonane-7-carboxylate
• CAS: 14891-11-3
• 化学式: C₉H₁₅NO₄
• mdl: MFCD25959224
• 分子量: 201.222
• InChiKey: MDCIVUFFPDJZRS-UHFFFAOYSA-N

物化性质

• 沸点：
  297.5±35.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.888
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4-二氧杂-7-氮杂螺[4.4]壬烷-7-羧酸,乙基酯 在 氢氧化钾 作用下， 生成 1,4-二氧杂-7-氮杂螺[4.4]壬烷
  参考文献：
  名称：

  番石榴碱：合成研究

  摘要：

  在利用1，2-二氢异喹啉中间体合成蛋氨酸的碳-氮骨架方面，描述了几种不成功的尝试。

  DOI：

  10.1016/s0040-4020(01)99398-6
• 作为产物：
  描述：

  1-乙氧羰基吡咯烷-3-酮 、 乙二醇 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 6.0h， 生成 1,4-二氧杂-7-氮杂螺[4.4]壬烷-7-羧酸,乙基酯
  参考文献：
  名称：

  番石榴碱：合成研究

  摘要：

  在利用1，2-二氢异喹啉中间体合成蛋氨酸的碳-氮骨架方面，描述了几种不成功的尝试。

  DOI：

  10.1016/s0040-4020(01)99398-6

文献信息

• [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。
• 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.
• Levisalles,J.; Rose,E., Bulletin de la Societe Chimique de France, 1976, p. 1947 - 1952
  作者：Levisalles,J.、Rose,E.

  DOI：——

  日期：——