(E)-4-乙酰氧基他莫昔芬 | 76117-70-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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: (E)-4-乙酰氧基他莫昔芬
• 英文名称: (E)-4-{1-[4-(2-dimethylaminoethoxy)phenyl]-2-phenylbut-1-enyl}phenyl acetate
• 英文别名: (E)-4-Acetoxy Tamoxifen；[4-[(E)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenyl] acetate
• CAS: 76117-70-9
• 化学式: C₂₈H₃₁NO₃
• 分子量: 429.559
• InChiKey: SGKPMDROJNZRQJ-BYYHNAKLSA-N

物化性质

• 熔点：
  98-100°C
• 沸点：
  538.7±50.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-4-乙酰氧基他莫昔芬 在 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 trans-4-Hydroxytamoxifen N-Glucuronide
  参考文献：
  名称：

  Quaternary ammonium-linked glucuronidation of trans-4-hydroxytamoxifen, an active metabolite of tamoxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4

  摘要：

  Tamoxifen (TAM), a nonsteroidal antiestrogen, is the most widely used drug for chemotherapy of hormone-dependent breast cancer in women. Trans-4-hydroxy-TAM (trans-4-HOTAM), one of the TAM metabolites in humans, has been considered to be an active metabolite of TAM because of its higher affinity toward estrogen receptors (ERs) than the parent drug and other side-chain metabolites. In the present study, we found a new potential metabolic pathway of trans-4-HO-TAM and its geometrical isomer, cis-4-HO-TAM, via N-linked glucuronic acid conjugation for excretion in humans. N+-Glucuronides of 4-HO-TAM isomers were isolated along with O-glucuronides from a reaction mixture consisting of trans- or cis-4-HO-TAM and human liver microsomes fortified with UDPglucuronic acid and identified with their respective synthetic specimens by high performance liquid chromatography-electrospray ionization time-of-flight mass spectrometry. Although N- and O-glucuronidating activities of human liver microsomes toward trans-4-HO-TAM were nearly comparable, O-glucuronidation was predominant for cis-4-HO-TAM conjugation. Only UGT1A4 catalyzed the N-linked glucuronidation. of 4-HO-TAM among recombinant human UGT isoforms (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17) expressed in insect cells. In contrast, all UGT isoforms, except for UGT1A3 and UGT1A4, catalyzed O-glucuronidation of 4-HO-TAM. Although O-glucuronidation of 4-HO-TAM greatly decreased binding affinity for human ERs, 4-HO-TAM N+-glucuronide still had binding affinity similar to 4-HO-TAM itself, suggesting that N+-glucuronide might contribute to the biological activity of TAM in vivo. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2006.01.004
• 作为产物：
  描述：

  乙酸酐 、 4-羟基三苯氧胺 反应 24.0h， 生成 (E)-4-乙酰氧基他莫昔芬
  参考文献：
  名称：

  Quaternary ammonium-linked glucuronidation of trans-4-hydroxytamoxifen, an active metabolite of tamoxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4

  摘要：

  Tamoxifen (TAM), a nonsteroidal antiestrogen, is the most widely used drug for chemotherapy of hormone-dependent breast cancer in women. Trans-4-hydroxy-TAM (trans-4-HOTAM), one of the TAM metabolites in humans, has been considered to be an active metabolite of TAM because of its higher affinity toward estrogen receptors (ERs) than the parent drug and other side-chain metabolites. In the present study, we found a new potential metabolic pathway of trans-4-HO-TAM and its geometrical isomer, cis-4-HO-TAM, via N-linked glucuronic acid conjugation for excretion in humans. N+-Glucuronides of 4-HO-TAM isomers were isolated along with O-glucuronides from a reaction mixture consisting of trans- or cis-4-HO-TAM and human liver microsomes fortified with UDPglucuronic acid and identified with their respective synthetic specimens by high performance liquid chromatography-electrospray ionization time-of-flight mass spectrometry. Although N- and O-glucuronidating activities of human liver microsomes toward trans-4-HO-TAM were nearly comparable, O-glucuronidation was predominant for cis-4-HO-TAM conjugation. Only UGT1A4 catalyzed the N-linked glucuronidation. of 4-HO-TAM among recombinant human UGT isoforms (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17) expressed in insect cells. In contrast, all UGT isoforms, except for UGT1A3 and UGT1A4, catalyzed O-glucuronidation of 4-HO-TAM. Although O-glucuronidation of 4-HO-TAM greatly decreased binding affinity for human ERs, 4-HO-TAM N+-glucuronide still had binding affinity similar to 4-HO-TAM itself, suggesting that N+-glucuronide might contribute to the biological activity of TAM in vivo. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2006.01.004

文献信息

• ERR MODULATORS AND USES THEREOF
  申请人：CITY OF HOPE

  公开号：US20180297923A1

  公开（公告）日：2018-10-18

  Disclosed herein, inter alia, are compositions and methods useful for treating non-alcoholic fatty liver diseases.

  披露的内容包括但不限于，用于治疗非酒精性脂肪肝疾病的组合物和方法。
• Compounds and methods for treating breast cancer and other diseases
  申请人：Forman Barry

  公开号：US20050096384A1

  公开（公告）日：2005-05-05

  Disclosed are novel compositions and novel methods for the creation of both the novel compounds and known compounds. Also disclosed are methods for use of the novel compounds for treating a variety of diseases relating to decreasing or preventing activation of estrogen receptors and/or estrogen related receptors.

  揭示了用于创造新化合物和已知化合物的新型组合物和新方法。还揭示了使用这些新化合物治疗与降低或预防雌激素受体和/或雌激素相关受体激活有关的各种疾病的方法。
• ERR modulators and uses thereof
  申请人：CITY OF HOPE

  公开号：US10590056B2

  公开（公告）日：2020-03-17

  Disclosed herein, inter alia, are compositions and methods useful for treating non-alcoholic fatty liver diseases.

  本文特别公开了用于治疗非酒精性脂肪肝的组合物和方法。
• COMPOUNDS AND METHODS FOR TREATING BREAST CANCER AND OTHER DISEASES
  申请人：Forman Barry

  公开号：US20090176305A1

  公开（公告）日：2009-07-09

  Disclosed are novel compositions and novel methods for the creation of both the novel compounds and known compounds. Also disclosed are methods for use of the novel compounds for treating a variety of diseases relating to decreasing or preventing activation of estrogen receptors and/or estrogen related receptors.
• US7531578B2
  申请人：——

  公开号：US7531578B2

  公开（公告）日：2009-05-12