2-氟-17-乙炔基雌二醇 | 22165-49-7

• 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
• 中文名称: 2-氟-17-乙炔基雌二醇
• 英文名称: 2-Fluoro-17α-ethynylestradiol
• 英文别名: 2-Fluoro-ethinylestradiol；2-fluoro-17α-ethinylestradiol；(8R,9S,13S,14S,17R)-17-ethynyl-2-fluoro-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol
• CAS: 22165-49-7
• 化学式: C₂₀H₂₃FO₂
• 分子量: 314.4
• InChiKey: OYMVHYFNQJXFGQ-BKRJIHRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氟-17-乙炔基雌二醇 在 偶氮二异丁腈 、 碘 、 三正丁基氢锡 作用下， 生成 2-fluoro-17α-vinylestradiol 、 2-Fluoro-(21Z)-(Iodovinyl)estradiol 、 2-Fluoro-(21E)-(Iodovinyl)estradiol
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00073a004
• 作为产物：
  描述：

  2-fluoroestrone 在 咪唑 、 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 2-氟-17-乙炔基雌二醇
  参考文献：
  名称：

  Regioselective synthesis of a-ring halogenated derivatives of 17α-ethynyloestradiol

  摘要：

  DOI：

  10.1016/s0040-4020(01)87092-7

文献信息

• US4605649A
  申请人：——

  公开号：US4605649A

  公开（公告）日：1986-08-12
• Regioselective synthesis of a-ring halogenated derivatives of 17α-ethynyloestradiol
  作者：Philip C. Bulman Page、Fazal Hussain、Nicholas M. Bonham、Paul Morgan、James L. Maggs、B.Kevin Park

  DOI：10.1016/s0040-4020(01)87092-7

  日期：1991.1
• 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.