4-fluoro-3-hydroxy-11β-methoxyestra-1,3,5(10)-trien-17-one | 151160-23-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 4-fluoro-3-hydroxy-11β-methoxyestra-1,3,5(10)-trien-17-one
• 英文别名: 4-fluoro-11β-methoxyestrone；(8S,9S,11S,13S,14S)-4-fluoro-3-hydroxy-11-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 151160-23-5
• 化学式: C₁₉H₂₃FO₃
• 分子量: 318.388
• InChiKey: HSGFRFZDQSLPQQ-LMZXCRDUSA-N

物化性质

• 沸点：
  447.3±45.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-fluoro-3-hydroxy-11β-methoxyestra-1,3,5(10)-trien-17-one 在 溶剂黄146 、 lithium tri-t-butoxyaluminum hydride 作用下， 生成 4-fluoro-11β-methoxy-3-O-methoxymethyl-16β,17β-O-sulfonylestra-1,3,5(10)-triene-3,16β,17β-triol
  参考文献：
  名称：

  Seimbille, Y.; Rousseau, J.; Benard, F., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S348 - S350

  摘要：

  DOI：
• 作为产物：
  描述：

  11β-methoxyestrone 在 三氟甲磺酸N-吡啶鎓 作用下， 以 1,1,2-三氯乙烷 为溶剂， 反应 24.0h， 生成 2-fluoro-3-hydroxy-11β-methoxyestra-1,3,5(10)-trien-17-one 、 4-fluoro-3-hydroxy-11β-methoxyestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  2,16α-和4,16α-二氟雌二醇及其11β-甲氧基衍生物的合成作为潜在的雌激素受体结合放射性药物

  摘要：

  我们通过两种不同的途径制备了2,16α-和4,16α-二氟雌二醇及其11β-甲氧基衍生物。第一条路线允许最终产品的大规模合成和表征，而第二条路线被选择用于氟化作用 作为便利的最后一步 贴标与寿命短的[ 18 F]氟。前一条路线涉及中间体双三甲基甲硅烷基烯醇醚和16α-氟雌酮的连续亲电氟化反应，然后进行减少异构体产物的17-酮分离和色谱分离。第二种途径是通过亲电取代雌酮或11β-甲氧基雌酮与N-氟吡啶鎓盐生成2-氟和4-氟衍生物，然后转化为反应性16β，17β-环硫酸盐。立体选择性开环硫酸盐 通过亲核的氟化作用使用Me 4 NF并随后去除保护层醚和硫酸盐基团通过快速水解 在酸性 乙醇得到所需的16α-氟衍生物。后一种方法可以容易地适于与放射性标记18通过取代我˚F 4 NF为18 ˚F -在乙腈。初步生物学数据表明，在16α-[ 18 F]氟雌​​二醇上同时添加了4-氟和11β-甲氧基（外语教学）可能会提供改进

  DOI：

  10.1039/b110021c

文献信息

• Synthesis of A-ring fluorinated derivatives of iodine-125-labeled (17.alpha.,20E/Z)-iodovinylestradiols: effect on receptor binding and receptor-mediated target tissue uptake
  作者：Hasrat Ali、Jacques Rousseau、Johan E. van Lier

  DOI：10.1021/jm00073a004

  日期：1993.10

  We have prepared a series of 2- and 4-fluoro derivatives of the isomeric (17alpha,20E)- and (17alpha,20Z)iodovinylestradiols (IVE2) and also the analogs substituted with either a 7alpha-methyl (7alpha-Me-IVE2) or 11beta-methoxy group (11beta-OMe-IVE2) and evaluated their in vitro and in vivo properties. Electrophilic substitution of the estrone derivatives with N-fluoropyridinium salt gave the 2- and 4-fluoro analogs which were subsequently converted to the 17alpha-ethynyl derivatives. The tributylstannyl intermediates were obtained from the corresponding 17alpha-ethynyl analogs using azobisisobutyronitrile or triethylborane as catalyst. All 12 products were also prepared as their no-carrier-added [I-125]iodovinyl analogs via destannylation of the tributylstannyl precursors. Binding affinity for the estrogen receptor (ER) was in general higher for the 4-F derivatives as compared to the 2-F derivatives, while the 20Z isomers of the same compounds showed somewhat higher ER binding affinity as compared to the 20E isomers. The combination of an A-ring fluoro and 7alpha- or 11beta-substituent decreased ER binding affinity. Substitution of a fluoro atom at C-4 on either the 17alpha-ethynylestradiol or isomeric 17alpha-IVE2 enhanced the affinity of the parent molecule for the ER. A-ring fluorination of all other analogues tested had no effect or depressed ER binding affinity. Varying incubation conditions showed substantial differences in ER binding kinetics between the 20E and 20Z isomers. Tissue distribution in immature female rats showed that the highest uterus uptake and uterus to blood/nontarget ratios in the IVE2 series were obtained with the 4-F-(17alpha,20Z)IVE2 isomer. The combination of A-ring fluoro and 7alpha- or 11beta-substitution decreased uterus uptake but had little or no effect on uterus to blood/nontarget ratios. The highest uterus to blood ratios were observed for the 4-F-(17alpha,20E)11beta-OMe-IVE2 (75 at 6 h and 125 at 12 h pi) reflecting rapid blood clearance and in vivo stability, as confirmed by the low levels of thyroid radioactivity. The lack of correlation between ER binding affinities and uterus uptake, and/or uptake ratios, suggests that other factors, including nonspecific binding and metabolic processes, also are involved in the tissue localization process. Our data suggest that 4-F substitution onto (17alpha,20Z)IVE2 and (17alpha,20E)11beta-OMe-IVE2 enhances the potential of these compounds to function as SPECT imaging agents of ER-rich tissues.
• Ali; Rousseau; Gantchev, Journal of Medicinal Chemistry, 1993, vol. 36, # 26, p. 4255 - 4263
  作者：Ali、Rousseau、Gantchev、Van Lier

  DOI：——

  日期：——
• Seimbille, Y.; Rousseau, J.; Benard, F., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S348 - S350
  作者：Seimbille, Y.、Rousseau, J.、Benard, F.、Ali, H.、Lier, J. E. van

  DOI：——

  日期：——
• Synthesis of 2,16α- and 4,16α-difluoroestradiols and their 11β-methoxy derivatives as potential estrogen receptor-binding radiopharmaceuticals
  作者：Yann Seimbille、Hasrat Ali、Johan E. van Lier

  DOI：10.1039/b110021c

  日期：2002.2.22

  fluorinations of intermediate bistrimethylsilyl enol ethers and 16α-fluoroestrones followed by reduction of the 17-ketone and chromatographic separation of the isomeric products. The second route proceeds via electrophilic substitution of estrone or 11β-methoxyestrone with N-fluoropyridinium salt to give the 2- and 4-fluoro derivatives followed by conversion to the reactive 16β,17β-cyclic sulfates. Stereoselective

  我们通过两种不同的途径制备了2,16α-和4,16α-二氟雌二醇及其11β-甲氧基衍生物。第一条路线允许最终产品的大规模合成和表征，而第二条路线被选择用于氟化作用 作为便利的最后一步 贴标与寿命短的[ 18 F]氟。前一条路线涉及中间体双三甲基甲硅烷基烯醇醚和16α-氟雌酮的连续亲电氟化反应，然后进行减少异构体产物的17-酮分离和色谱分离。第二种途径是通过亲电取代雌酮或11β-甲氧基雌酮与N-氟吡啶鎓盐生成2-氟和4-氟衍生物，然后转化为反应性16β，17β-环硫酸盐。立体选择性开环硫酸盐 通过亲核的氟化作用使用Me 4 NF并随后去除保护层醚和硫酸盐基团通过快速水解 在酸性 乙醇得到所需的16α-氟衍生物。后一种方法可以容易地适于与放射性标记18通过取代我˚F 4 NF为18 ˚F -在乙腈。初步生物学数据表明，在16α-[ 18 F]氟雌​​二醇上同时添加了4-氟和11β-甲氧基（外语教学）可能会提供改进