4-羟基他莫昔芬 | 82413-23-8

• 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: 4-羟基他莫昔芬
• 中文别名: 4-溴-N-[(2E)-1-甲基吡咯烷-2-亚基]苯胺
• 英文名称: (Z)-4-hydroxytamoxifen
• 英文别名: 4'-Hydroxytamoxifen；(Z)-4-trans-hydroxytamoxifen；trans-4'-hydroxytamoxifen；Z-4-hydroxytamoxifen；4-hydroxytamoxifen；4-[(Z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol
• CAS: 82413-23-8
• 化学式: C₂₆H₂₉NO₂
• 分子量: 387.522
• InChiKey: DODQJNMQWMSYGS-QPLCGJKRSA-N

物化性质

• 熔点：
  150-153°C
• 沸点：
  514.4±50.0 °C(Predicted)
• 密度：
  1.092±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、二氯甲烷、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

4'-羟基他莫昔芬是他莫昔芬的一个已知人体代谢物。

4'-Hydroxytamoxifen is a known human metabolite of tamoxifen.

来源:NORMAN Suspect List Exchange

安全信息

• 储存条件：
  -20°C，密封保存，置于干燥处。

制备方法与用途

4-羟基他莫昔芬是五种主要的他莫昔芬I期代谢物之一，它在乳腺中是一种知名的雌激素受体拮抗剂，在子宫内则部分表现为雌激素受体激动剂。

反应信息

• 作为产物：
  描述：

  2-(4-羟基苯基)-1-苯基- 在 盐酸 、 硫酸 、 乙基溴化镁 作用下， 反应 14.0h， 生成 4-羟基他莫昔芬
  参考文献：
  名称：

  Estrogenic and antiestrogenic activity of monophenolic analogs of tamoxifen, [(Z)-2-[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine]

  摘要：

  Five hydroxylated analogues of tamoxifen [1, (Z)-2-[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine] and its geometric isomer were prepared by reaction of protected hydroxy-alpha-ethyldeoxybenzoins with 4-[2-dimethylamino) ethoxy]phenylmagnesium bromide, followed by acid-catalyzed dehydration-deprotection and chromatographic separation of isomer mixtures. Estrogen receptor binding affinity and estrogenic and antiestrogenic activity of each of the compounds were determined in the rat, in comparison with 4-hydroxytamoxifen (2). The new compounds had a wide range of receptor binding affinities, with that of 3-hydroxytamoxifen (6c), the most strongly bound, approaching that of estradiol. The trans isomers 6a,b were more strongly bound than were the cis isomers 7a,b. Antiestrogenic activity was seen in all compounds except 7b. This was also true for estrogenic activity, except that in 6c this activity was also substantially reduced. Maximal antiestrogenic effectiveness of 6c occurred at a 10-fold greater daily dose (50 micrograms/rat) than that required for maximal effect of 2.

  DOI：

  10.1021/jm00351a010

文献信息

• Synthesis of Tetrasubstituted Alkenes by Stereo- and Regioselective Stannyllithiation of Diarylacetylenes
  作者：Hayato Tsuji、Yasuyuki Ueda、Laurean Ilies、Eiichi Nakamura

  DOI：10.1021/ja1059119

  日期：2010.9.1

  formed C-metal bonds can be sequentially and stereospecifically transformed into two new C-C bonds as illustrated by stereoselective synthesis of 4-hydroxytamoxifen and its regioisomer. A tetraarylethene bearing different aryl groups can be synthesized similarly and cyclized to a substituted dibenzo[g,p]chrysene derivative via a palladium-catalyzed arylation reaction.

  三甲基锡锂与二芳基乙炔的加成仅以反方式发生以产生锂硫乙烯基锡烷中间体。加成的区域选择性受乙炔的空间和电子性质控制，最高可达 >99:1。如 4-羟基三苯氧胺及其区域异构体的立体选择性合成所示，两个新形成的 C-金属键可以依次立体定向地转化为两个新的 CC 键。带有不同芳基的四芳基乙烯可以类似地合成并通过钯催化的芳基化反应环化为取代的二苯并[g,p]芘衍生物。
• QUANTITATION OF TAMOXIFEN AND METABOLITES THEREOF BY MASS SPECTROMETRY
  申请人：QUEST DIAGNOSTICS INVESTMENTS INCORPORATED

  公开号：US20150323513A1

  公开（公告）日：2015-11-12

  Provided are methods for determining the amount of tamoxifen and its metabolites in a sample by mass spectrometry. In some aspects, the methods provided herein comprise determining the amount of norendoxifen. In some aspects, the methods provided herein comprise determining the amount of norendoxifen and tamoxifen. In some aspects, the methods provided herein comprise determining the amount of norendoxifen and other tamoxifen metabolites. In some aspects, the methods provided herein comprise determining the amount of tamoxifen, norendoxifen, and other tamoxifen metabolites.

  本文提供了一种利用质谱法测定样品中的他莫昔芬及其代谢物含量的方法。 在某些方面，本文提供的方法包括测定诺瑞雌酮的含量。 在某些方面，本文提供的方法包括测定诺瑞雌酮和他莫昔芬的含量。 在某些方面，本文提供的方法包括测定诺瑞雌酮和其他他莫昔芬代谢物的含量。 在某些方面，本文提供的方法包括测定他莫昔芬、诺瑞雌酮和其他他莫昔芬代谢物的含量。
• Composition for and method of preventing or treating breast cancer
  申请人：Protein Technologies International, Inc.

  公开号：EP1159963A1

  公开（公告）日：2001-12-05

  The present invention is a composition for preventing, minimising, or reversing the development or growth of breast cancer. The composition contains a combination of a selective estrogen receptor modulator selected from at least one of raloxifene, droloxifene, toremifene, 4'-iodotamoxifen, and idoxifene and at least one isoflavone selected from genistein, daidzein, biochanin A, formononetin, and their respective naturally occurring glucosides and glucoside conjugates. The present invention also provides a method of preventing, minimising, or reversing the development or growth of breast cancer in which a selective estrogen receptor modulator selected from at least one of raloxifene, droloxifene, toremifene, 4'-iodotamoxifen, and idoxifene is co-administered with at least one isoflavone selected from genistein, daidzein, biochanin A, formononetin, and their naturally occurring glucosides and glucoside conjugates to a woman having or predisposed to having breast cancer.

  本发明是一种用于预防、减少或逆转乳腺癌发展或生长的组合物。该组合物包含一种选择性雌激素受体调节剂的组合，该选择性雌激素受体调节剂选自雷洛昔芬、屈洛昔芬、托瑞米芬、4'-碘他莫昔芬和伊多昔芬中的至少一种，以及至少一种异黄酮，该异黄酮选自genistein、daidzein、biochanin A、formononetin，以及它们各自天然存在的葡萄糖苷和葡萄糖苷结合物。本发明还提供了一种预防、减少或逆转乳腺癌发展或生长的方法，在该方法中，选自雷洛昔芬（raloxifene）、屈洛昔芬（droloxifene）、托瑞米芬（toremifene）、4'-碘他莫昔芬（4'-iodotamoxifen）中至少一种的选择性雌激素受体调节剂与伊多昔芬（idoxifene）同时服用、和依多昔芬中的至少一种异黄酮共同施用给患乳腺癌或易患乳腺癌的妇女。
• Method for identifying active and/or inactive metobolites; and novel active metabolites
  申请人：Kiadis B.V.

  公开号：EP1505395A1

  公开（公告）日：2005-02-09

  The present invention relates to a method for determining whether or not a metabolite of a particular lead compound is an active or an inactive compound. Particularly, this method allows an early screening on whether or not a lead compound itself or an active metabolite thereof is a suitable candidate to go through the time- and money consuming route to try and obtain a valuable and marketable pharmaceutical composition. In a second, aspect, the present invention relates to active metabolites found by carrying out the method of the invention.

  本发明涉及一种确定特定先导化合物的代谢物是活性化合物还是非活性化合物的方法。特别是，这种方法可以及早筛选出先导化合物本身或其活性代谢物是否适合通过耗时耗钱的途径来尝试获得有价值和可销售的药物组合物。第二方面，本发明涉及通过实施本发明方法发现的活性代谢物。
• Use of fulvestrant in the treatment of resistant breast cancer
  申请人：AstraZeneca AB

  公开号：EP1586323A1

  公开（公告）日：2005-10-19

  The invention relates to the use of fulvestrant in the treatment of breast cancer in patients who have previously been treated with an Selective Estrogen Receptor Modulator (SERM) and an aromatase inhibitor.

  本发明涉及氟维司群在乳腺癌治疗中的应用，患者之前曾接受过选择性雌激素受体调节剂（SERM）和芳香化酶抑制剂的治疗。