2-methoxy-3-O-benzylestradiol 17-O-sulfamate | 923029-65-6

• 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: 2-methoxy-3-O-benzylestradiol 17-O-sulfamate
• 英文别名: 2-methoxy-3-benzyloxyestra-1,3,5(10)-trien-17β-yl sulfamate；[(8R,9S,13S,14S,17S)-2-methoxy-13-methyl-3-phenylmethoxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] sulfamate
• CAS: 923029-65-6
• 化学式: C₂₆H₃₃NO₅S
• 分子量: 471.618
• InChiKey: KBCHUGSPIPUMGU-IASQOJPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  96.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methoxy-3-O-benzylestradiol 17-O-sulfamate 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 32.0h， 生成 [(8R,9S,13S,14S,17S)-3-hydroxy-2-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] N,N-dimethylsulfamate
  参考文献：
  名称：

  2-Substituted Estradiol Bis-sulfamates, Multitargeted Antitumor Agents:  Synthesis, In Vitro SAR, Protein Crystallography, and In Vivo Activity

  摘要：

  The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though COMPARE analysis of activity profiles was negative. 21 was cocrystallized with carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination of the 17-O-sulfamate of 21 to the active site zinc and a probable additional lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates for further development as multitargeted anticancer agents.

  DOI：

  10.1021/jm060705x
• 作为产物：
  描述：

  2-甲氧基雌二醇 在 氨基磺酰氯 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 11.0h， 生成 2-methoxy-3-O-benzylestradiol 17-O-sulfamate
  参考文献：
  名称：

  2-Substituted Estradiol Bis-sulfamates, Multitargeted Antitumor Agents:  Synthesis, In Vitro SAR, Protein Crystallography, and In Vivo Activity

  摘要：

  The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though COMPARE analysis of activity profiles was negative. 21 was cocrystallized with carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination of the 17-O-sulfamate of 21 to the active site zinc and a probable additional lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates for further development as multitargeted anticancer agents.

  DOI：

  10.1021/jm060705x

文献信息

• 2-甲氧基雌二醇类似物及其制备方法与用途
  申请人：郑州大学

  公开号：CN103772463B

  公开（公告）日：2016-06-22

  本发明涉及2-甲氧基雌二醇类似物及其制备方法与用途，可有效解决2-甲氧基雌二醇类似物的制备及实现2-甲氧基雌二醇类似物在制备抗肿瘤药物中的应用，方法是，以2-甲氧基-3-苄氧基-雌甾-1,3,5(10)-三烯-17β-醇或17β-胺为原料，溶于有机溶剂中，在Lewis碱存在下与化合物（1）进行酰化反应得到2-甲氧基-3-苄氧基-雌甾-1,3,5(10)-三烯-17β-酯或17β-酰胺化合物（2），然后经催化加氢反应得到化合物（3），最后再经酰化反应或烃化反应得到化合物2-甲氧基雌二醇类似物（4），反应式为：本发明2-甲氧基雌二醇类似物的制备方法简单，条件温和，收率高，可有效用于抗肿瘤药物制剂的开发。
• 2-Substituted Estradiol Bis-sulfamates, Multitargeted Antitumor Agents:  Synthesis, In Vitro SAR, Protein Crystallography, and In Vivo Activity
  作者：Mathew P. Leese、Bertrand Leblond、Andrew Smith、Simon P. Newman、Anna Di Fiore、Giuseppina De Simone、Claudiu T. Supuran、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm060705x

  日期：2006.12.1

  The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though COMPARE analysis of activity profiles was negative. 21 was cocrystallized with carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination of the 17-O-sulfamate of 21 to the active site zinc and a probable additional lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates for further development as multitargeted anticancer agents.