2-[4-[(Z)-1,2-二苯基丁-1-烯基]苯氧基]乙基-三甲基铵碘化物 | 107256-99-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 2-[4-[(Z)-1,2-二苯基丁-1-烯基]苯氧基]乙基-三甲基铵碘化物
• 中文别名: 二十四烷酸钙
• 英文名称: Tamoxifen methiodide
• 英文别名: 2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]ethyl-trimethylazanium;iodide
• CAS: 107256-99-5
• 化学式: C₂₇H₃₂NO*I
• 分子量: 513.462
• InChiKey: PXJJOGITBQXZEQ-JTHROIFXSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  他莫昔芬 、 碘甲烷 以 丙酮 为溶剂， 反应 48.0h， 以87%的产率得到2-[4-[(Z)-1,2-二苯基丁-1-烯基]苯氧基]乙基-三甲基铵碘化物
  参考文献：
  名称：

  杯胆碱介导的胆碱结合物的液体膜运输2：药物-胆碱结合物和神经递质的运输。

  摘要：

  下边缘羧酸杯[n]芳烃和上边缘膦酸官能化杯[4]芳烃影响不同分子有效负载通过液膜的选择性转运。成功的秘诀在于受体互补手柄的连接。我们发现胆碱中存在的三甲基铵乙烯基团是药物和类药物物种运输的一般处理方法。此外，还运输了具有可电离胺端的神经递质。随着有效载荷变得越来越亲脂，已经发现了该策略的一些局限性。这些进展揭示了在囊泡和细胞系统中合成受体介导的选择性小分子转运的新方法。

  DOI：

  10.1002/ejoc.201403519
• 作为试剂：
  描述：

  他莫昔芬 、 碘甲烷 在 2-[4-[(Z)-1,2-二苯基丁-1-烯基]苯氧基]乙基-三甲基铵碘化物 、 甲醇 作用下， 以 乙酸乙酯 为溶剂， 反应 24.0h， 以to yield >99% tamoxifen methiodide的产率得到2-[4-[(Z)-1,2-二苯基丁-1-烯基]苯氧基]乙基-三甲基铵碘化物
  参考文献：
  名称：

  Enhanced anti-angiogenic activity of permanently charged derivatives of steroid hormones

  摘要：

  本发明揭示了永久带电的类固醇激动剂或拮抗剂的使用，作为强效的抗血管生成组合物，其包含一种通式I、II或III的化合物作为活性成分：其中DRUG是任何类固醇激动剂或拮抗剂、混合激动剂-拮抗剂或部分激动剂，取代基如规范所定义。

  公开号：

  US06387955B1

文献信息

• Enhanced anti-angiogenic activity of permanently charged derivatives of
  申请人：Pharmos Corporation

  公开号：US06083990A1

  公开（公告）日：2000-07-04

  The present invention discloses the use of permanently charged steroid agonists or antagonists as potent anti-angiogenic compositions comprising as an active ingredient a compound of the general formulae I, II or III: ##STR1## wherein DRUG is any steroid agonist or antagonist, a mixed agonist-antagonist, or a partial agonist and the substituents are as defined in the specification.

  本发明揭示了永久带电的类固醇激动剂或拮抗剂的使用作为强效抗血管生成组合物，其包括作为活性成分的一种通式I、II或III化合物：##STR1## 其中DRUG是任何类固醇激动剂或拮抗剂，混合激动剂-拮抗剂，或部分激动剂，取代基如规范中所定义。
• Genomic action of permanently charged tamoxifen derivatives via estrogen receptor-α
  作者：Claudia Rivera-Guevara、Víctor Pérez-Alvarez、Rocío García-Becerra、David Ordaz-Rosado、Martha Sonia Morales-Ríos、Elizabeth Hernández-Gallegos、Austin J. Cooney、María Elena Bravo-Gómez、Fernando Larrea、Javier Camacho

  DOI：10.1016/j.bmc.2010.06.039

  日期：2010.8

  Tamoxifen is a selective estrogen receptor modulator widely used in oncology and reproductive endocrinology. In order to decrease its non-desirable effects and elucidate mechanisms of action, permanently charged tamoxifen derivatives (PCTDs) have been reported. Whether PCTDs have genomic effects remains controversial. Since the clinical relevance of tamoxifen, the necessity to have new anticancer drugs, and in order to gain insights into the mechanisms of action of PCTDs, we obtained six quaternary ammonium salts derived from tamoxifen including three new compounds. We characterized them by nuclear magnetic resonance, X-ray diffraction, electron microscopy, and/or high performance liquid chromatography, and detected them in cell lysates by liquid chromatography coupled to mass spectrometry. We evaluated their binding to estrogen receptor-alpha (ER alpha, their effect on the transcriptional activity mediated by ER alpha (gene reporter assays), and the proliferation of cancer cells (MCF-7 and cells from a cervical cancer primary culture). Structural studies demonstrated the expected identity of the molecules. All PCTDs did bind to ER alpha, one of them induced ER alpha-mediated transcription while two others inhibited such genomic action. Accordingly, PCTDs were detected in cell lysates. PCTDs inhibited cell proliferation, noteworthy, two of them displayed higher inhibition than tamoxifen. Structure-activity analysis suggests that PCTDs permanent positive charge and the length of the aliphatic chain might be associated to the biological responses studied. We suggest genomic effects as a mechanism of action of PCTDs. The experimental approaches here used could lead to a better design of new therapeutic molecules and help to elucidate molecular mechanisms of new anticancer drugs. (C) 2010 Elsevier Ltd. All rights reserved.