2-methoxy-3-hydroxy-17β-methylsulfonylaminoestra-1,3,5(10)-triene | 880649-06-9

• 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-hydroxy-17β-methylsulfonylaminoestra-1,3,5(10)-triene
• 英文别名: N-[(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]methanesulfonamide
• CAS: 880649-06-9
• 化学式: C₂₀H₂₉NO₄S
• 分子量: 379.521
• InChiKey: MHOHISHFHDMHMU-BKRJIHRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  84
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methoxy-3-hydroxy-17β-methylsulfonylaminoestra-1,3,5(10)-triene 在 氨基磺酰氯 作用下， 以 异丁酰胺 为溶剂， 反应 16.0h， 以78%的产率得到2-methoxy-3-O-sulfamoyl-17β-methylsulfonylaminoestra-1,3,5(10)-triene
  参考文献：
  名称：

  2-甲氧基雌二醇-3,17- O，O-双-氨基磺酸酯类似物的合成，抗微管蛋白和抗增殖SAR

  摘要：

  讨论了雌二醇3，17- O，O-双-氨基磺酸酯（E2bisMATEs）类似物的合成和抗增殖活性。C-17取代基的修饰表明，H键受体对于高抗增殖活性至关重要。该H键受体所处的局部环境可以在一定程度上变化。C-17-氧连接基可以被缺失或被电子中性的亚甲基取代，并且末端NH 2被甲基取代也是可接受的。甲磺酸酯10和14被证明与E2bisMATE 2和3等价，而砜20和35显示出增强的体外抗增殖活性。另外，首次建立了2-取代的雌二醇-3 - O-氨基磺酸衍生物作为微管蛋白聚合抑制剂的SAR 。这些试剂抑制放射性标记的秋水仙碱与微管蛋白的结合。

  DOI：

  10.1021/jm9018806
• 作为产物：
  描述：

  2-methoxy-3-benzyloxyestra-1,3,5(10)-triene-17β-amine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 60.0 ℃ 、206.85 kPa 条件下， 反应 4.0h， 生成 2-methoxy-3-hydroxy-17β-methylsulfonylaminoestra-1,3,5(10)-triene
  参考文献：
  名称：

  Design, synthesis and antiproliferative effect of 17β-amide derivatives of 2-methoxyestradiol and their studies on pharmacokinetics

  摘要：

  A series of 17 beta-amide-2-methoxyestradiol compounds were synthesized with an aim to enhance the anti proliferative effect of 2-methoxyestradiol. The antiproliferative activity of 2-methoxyestradiol analogs against human cancer cells was investigated. 2-methoxy-3-benzyloxy-17 beta-chloroacetamide-1,3,5(10)-triene (5e) and 2-methoxy-3-hydroxy-1713-butyramide-1,3,5(10)-triene (6c) had comparable or better antitumor activity than 2-methoxyestradiol. The elimination half-life of 6c (t(1/2 beta) = 240.93 min) is ten times longer than 2-ME and the area under the curve was seven times (AUC(0-tmin) = 2068.20 +/- 315.74 lig mL(-1) min) higher than 2-ME, respectively. Whereas 5e had similar pharmacokinetic behavior with 2-ME (t(1/2 beta) = 22.28 min) with a t(1/2 beta) of 29.5 min. 6c had higher blood concentration, longer actuation duration and better suppression rate against 5180 mouse ascites tumor than 2-methoxyestradiol.

  DOI：

  10.1016/j.steroids.2017.09.013

文献信息

• Design, synthesis and antiproliferative effect of 17β-amide derivatives of 2-methoxyestradiol and their studies on pharmacokinetics
  作者：Xiufang Shi、Zhihao Wang、Feng Xu、Xiang Lu、Haifeng Yao、Dandan Wu、Shuaijun Sun、Ruifang Nie、Shuo Gao、Panpan Li、Liwen Xia、Zhenzhong Zhang、Cong Wang

  DOI：10.1016/j.steroids.2017.09.013

  日期：2017.12

  A series of 17 beta-amide-2-methoxyestradiol compounds were synthesized with an aim to enhance the anti proliferative effect of 2-methoxyestradiol. The antiproliferative activity of 2-methoxyestradiol analogs against human cancer cells was investigated. 2-methoxy-3-benzyloxy-17 beta-chloroacetamide-1,3,5(10)-triene (5e) and 2-methoxy-3-hydroxy-1713-butyramide-1,3,5(10)-triene (6c) had comparable or better antitumor activity than 2-methoxyestradiol. The elimination half-life of 6c (t(1/2 beta) = 240.93 min) is ten times longer than 2-ME and the area under the curve was seven times (AUC(0-tmin) = 2068.20 +/- 315.74 lig mL(-1) min) higher than 2-ME, respectively. Whereas 5e had similar pharmacokinetic behavior with 2-ME (t(1/2 beta) = 22.28 min) with a t(1/2 beta) of 29.5 min. 6c had higher blood concentration, longer actuation duration and better suppression rate against 5180 mouse ascites tumor than 2-methoxyestradiol.
• Synthesis, Antitubulin, and Antiproliferative SAR of Analogues of 2-Methoxyestradiol-3,17-<i>O</i>,<i>O</i>-bis-sulfamate
  作者：Fabrice Jourdan、Mathew P. Leese、Wolfgang Dohle、Ernest Hamel、Eric Ferrandis、Simon P. Newman、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm9018806

  日期：2010.4.8

  The synthesis and antiproliferative activity of analogues of estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent reveal that an H-bond acceptor is essential for high antiproliferative activity. The local environment in which this H-bond acceptor lies can be varied to an extent. The C-17-oxygen linker can be deleted or substituted with an electronically

  讨论了雌二醇3，17- O，O-双-氨基磺酸酯（E2bisMATEs）类似物的合成和抗增殖活性。C-17取代基的修饰表明，H键受体对于高抗增殖活性至关重要。该H键受体所处的局部环境可以在一定程度上变化。C-17-氧连接基可以被缺失或被电子中性的亚甲基取代，并且末端NH 2被甲基取代也是可接受的。甲磺酸酯10和14被证明与E2bisMATE 2和3等价，而砜20和35显示出增强的体外抗增殖活性。另外，首次建立了2-取代的雌二醇-3 - O-氨基磺酸衍生物作为微管蛋白聚合抑制剂的SAR 。这些试剂抑制放射性标记的秋水仙碱与微管蛋白的结合。