2-methoxy-3-benzyloxyestra-1,3,5(10)-triene-17β-amine | 880649-02-5

• 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: 2-methoxy-3-benzyloxyestra-1,3,5(10)-triene-17β-amine
• 英文别名: 2-methoxy-3-O-benzyl-17β-aminoestra-1,3,5(10)-triene；(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-amine
• CAS: 880649-02-5
• 化学式: C₂₆H₃₃NO₂
• 分子量: 391.554
• InChiKey: SNOHIMBZKQYHBO-IASQOJPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
  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
• 作为产物：
  描述：

  2-methoxy-3-O-benzylestra-1,3,5(10)-triene-17-oxime 在 sodium tetrahydroborate 、 molybdenum(VI) oxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以85%的产率得到2-methoxy-3-benzyloxyestra-1,3,5(10)-triene-17β-amine
  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

文献信息

• 2-甲氧基雌二醇-17β-脯氨酰胺类似物、合成方法及其应用
  申请人：郑州大学

  公开号：CN111171102B

  公开（公告）日：2022-04-01

  本发明属药物化学领域，涉及2‑甲氧基雌二醇‑17β‑脯氨酰胺类似物、合成方法及其应用。其具有如下结构通式：其中，m=0,1,2;n=0,1,2;r=0,1,2;X=H,OH,F,Cl,Br,OSO2NH2；Y=C,O,S,N；R1=H,SO2NH2；R2=H,Me,Et,Ac；经体外抗肿瘤细胞增殖活性试验研究证明，该类衍生物保持或增强了抗肿瘤细胞的活性，并且相对于2‑甲氧基雌二醇，水溶性显著增加，具有较好的成药性，并且药物体内代谢半衰期达4小时左右，药物体内生物利用度也明显改善，可用于抗肿瘤药物制剂的开发。
• 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。