(17beta)-3,17-二(甲氧基甲氧基)雌甾-1(10),2,4-三烯-2-醇 | 217792-89-7

• 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: (17beta)-3,17-二(甲氧基甲氧基)雌甾-1(10),2,4-三烯-2-醇
• 英文名称: (8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-ol
• 英文别名: 2-hydroxyestradiol-3,17β-O,O-bis(methoxymethyl)ether；2-hydroxy-3,17β-O,O-bis(methoxymethyl)estradiol；2-hydroxy-3,17-β-O-bis(methoxymethyl)estradiol；2-hydroxy-3,17β-O-bis(methoxymethyl)estradiol；2-hydroxy-3,17-O-bis(methoxymethyl)estradiol；3,17β-bis(methoxymethoxy)estra-1,3,5-triene-2-ol；2-Hydroxy-3,17|A-O-bis(methoxymethyl)estradiol；(8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-2-ol
• CAS: 217792-89-7
• 化学式: C₂₂H₃₂O₅
• 分子量: 376.493
• InChiKey: XXXVHIQGIYOGRK-HIFDQRORSA-N

物化性质

• 沸点：
  494.4±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (17beta)-3,17-二(甲氧基甲氧基)雌甾-1(10),2,4-三烯-2-醇 在 盐酸 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-甲氧基雌二醇
  参考文献：
  名称：

  合成 2-[11C] 甲氧基-3,17β-O,O-双（氨磺酰基）雌二醇作为一种新的潜在 PET 试剂，用于在癌症中对类固醇硫酸酯酶 (STS) 进行成像

  摘要：

  类固醇硫酸酯酶 (STS) 催化类固醇硫酸盐水解为雌酮，雌酮是肿瘤中雌激素的主要来源。碳酸酐酶 II (CAII) 通过氨基磺酸部分的单阴离子形式与酶活性位点中的锌原子配位而在红细胞中高表达，并且 CAII 在多种肿瘤中高表达。2-Methoxy-3,17β-O,O-双（氨磺酰基）雌二醇 (5) 是一种双功能 STS-CAII 抑制剂，可选择性地抑制 STS，其 IC(50) 值为 39 nMIC(50)，而 CAII 值为 379 nMIC(50) . 该化合物在 NCI 60 细胞系面板中表现出强大的抗增殖活性，平均图中点值为 87 nM，在早期 Lewis 肺模型中也具有体外和体内抗血管生成活性。该化合物最近已被开发为多靶点抗癌剂。STS 和 CAII 在癌症中都过表达，并已成为癌症治疗和癌症分子成像的有吸引力的靶标。在这里，我们报告了 2-[(11)C] 甲氧基-3,17β-O,O

  DOI：

  10.1016/j.steroids.2012.04.007
• 作为产物：
  描述：

  雌二醇 在 仲丁基锂 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 反应 25.0h， 生成 (17beta)-3,17-二(甲氧基甲氧基)雌甾-1(10),2,4-三烯-2-醇
  参考文献：
  名称：

  Synthesis of 2-[11C]methoxy-3,17β-estradiol to measure the pharmacokinetics of an antitumor drug candidate, 2-methoxy-3,17β-estradiol

  摘要：

  2-甲氧基-3,17β-雌二醇是一种内源性雌激素代谢物，在多种癌细胞系中显示出细胞毒性，还具有抗血管生成和促细胞凋亡活性。目前正在进行 2-甲氧基-3,17β-雌二醇治疗多发性骨髓瘤、晚期实体瘤、转移性乳腺癌和前列腺癌的 I 期和 II 期临床试验。我们制备了 2-[11C]甲氧基-3,17β-雌二醇，用于测量临床试验中 2-甲氧基-3,17β-雌二醇的药代动力学和器官分布。2-[11C]Methoxy-3,17β-estradiol 由前体 2-羟基-3,17β-O-双（甲氧基甲基）雌二醇分两步合成，放射化学纯度超过 99%。整个反应时间为 45 分钟，衰变校正放射化学收率为 32.9%。在 pH 值为 7.4 时，2-[11C]甲氧基-3,17β-雌二醇的分布系数（logP7.4）为 2.95。Copyright © 2006 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.1131

文献信息

• Synthesis and in vitro evaluation of 2-[11C]methoxyestradiol-3,17β-O,O-bissulfamate for in vivo studies of angiogenesis
  作者：Choong Mo Kang、Yearn Seong Choe、Kyung-Ho Jung、Joon Young Choi、Kyung-Han Lee、Byung-Tae Kim

  DOI：10.1002/jlcr.1930

  日期：2011.11

  In the present study, 2-methoxyestradiol-3,17β-O,O-bissulfamate (1), a known angiogenesis inhibitor, was prepared in a radiolabeled form by 11C-methylation of 2-hydroxyestradiol-3,17β-O,O-bis(N-trityl)sulfamate (6) followed by detritylation. Synthesis of precursor 6 required a rather long step because of the presence of two sulfamoyl groups. The decay-corrected radiochemical yield of [11C]1 was 19 ± 2% based on [11C]CH3I, and the specific activity was 34–39 GBq/µmol. Although 1 is known to significantly inhibit the proliferation of human umbilical vascular endothelial cells (HUVECs), its radiolabeled form, [11C]1 was not avidly taken up by HUVECs, and the uptake increased slightly in a time-dependent manner (156% at 60 min relative to a value of 100% at 5 min). These results suggest that further studies are warranted to determine the molecular target for [11C]1. Copyright © 2011 John Wiley & Sons, Ltd.

  在本研究中，通过11C甲基化2-羟基雌二醇-3,17β-O,O-双(N-三苯基)磺酰胺（6）并随后脱三苯基化，制备了已知的血管生成抑制剂2-甲氧基雌二醇-3,17β-O,O-双磺酰胺（1）的放射性标记形式。由于存在两个磺酰胺基团，前体6的合成需要较长的步骤。基于[11C]CH3I的衰变校正放射化学产率为19±2%，比活度为34-39 GBq/µmol。虽然已知1显著抑制人脐静脉内皮细胞（HUVECs）的增殖，但其放射性标记形式[11C]1并未被HUVECs大量摄取，摄取量随时间轻微增加（60分钟时相对于5分钟的100%为156%）。这些结果表明有必要进一步研究以确定[11C]1的分子靶标。版权所有 © 2011 John Wiley & Sons, Ltd.
• B-homoestra-1,3,5(10)-trienes as modulators of tubulin polymerization
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US06696436B1

  公开（公告）日：2004-02-24

  The invention provides B-ring expanded estra-1,3,5(10)-triene compounds of general formula (1) which modulate the polymerization of tubulin and/or the depolymerization of microtubules. The compounds have anti-angiogenic and anti-tumor activity. The invention also provides methods of preparing the compounds, and methods of using the compounds for the treatment of cancer or other mammalian diseases characterized by undesirable angiogenesis. The compounds of the invention are also expected to have utility as research tools.

  该发明提供了一般式（1）的B环扩展的雌甾-1,3,5（10）-三烯化合物，可以调节微管蛋白聚合或微管蛋白解聚。这些化合物具有抗血管生成和抗肿瘤活性。该发明还提供了制备这些化合物的方法，以及利用这些化合物治疗癌症或其他由不良血管生成特征的哺乳动物疾病的方法。该发明的化合物还预计可作为研究工具使用。
• The Effect of Exchanging Various Substituents at the 2-Position of 2-Methoxyestradiol on Cytotoxicity in Human Cancer Cell Cultures and Inhibition of Tubulin Polymerization
  作者：Mark Cushman、Arasambattu K. Mohanakrishnan、Melinda Hollingshead、Ernest Hamel

  DOI：10.1021/jm020218r

  日期：2002.10.1

  A new set of estradiol derivatives bearing various substituents at the 2-position were synthesized in order to further elucidate the structural parameters associated with the antitubulin activity and cytotoxicity of 2-substituted estradiols. The potencies of the new compounds as inhibitors of tubulin polymerization were determined, and the cytotoxicities of the analogues in human cancer cell cultures were investigated. The substituents introduced into the 2-position of estradiol included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, 3-N,N-dimethylaminoethylideneamino, 2'-hydroxyethylineneamino, (beta-3,4,5-trimethoxyphenyl)ethenyl, phenylethynyl, ethynly, 1'-propynyl, and cyano. The substituents conferring the ability to inhibit tubulin polymerization included E-3'-hydroxy-1'-propenyl, 2'-hydroxyethoxy, ethynyl, and 1'-propynyl. The remaining compounds were all inactive as inhibitors of tubulin polymerization when tested at concentrations of up to 40 muM. All of the compounds were cytotoxic in a panel of 55 human cancer cell cultures, and in general, the most cytotoxic compounds were also the most potent as inhibitors of tubulin polymerization. 2-(1'-Propynyl)estradiol displayed significant anticancer activity in the in vivo hollow fiber animal model.
• Effects of Altering the Electronics of 2-Methoxyestradiol on Cell Proliferation, on Cytotoxicity in Human Cancer Cell Cultures, and on Tubulin Polymerization
  作者：Allison B. Edsall、Arasambattu K. Mohanakrishnan、Donglai Yang、Philip E. Fanwick、Ernest Hamel、Arthur D. Hanson、Gregory E. Agoston、Mark Cushman

  DOI：10.1021/jm049647a

  日期：2004.10.1

  A series of new analogues of 2-methoxyestradiol (1) were synthesized to further elucidate the relationships between structure and activity. The compounds were designed to diminish the potential for metabolic deactivation at positions 2 and 17 and were analyzed as inhibitors of tubulin polymerization and for cytotoxicity. 17alpha-Methyl-beta-estradiol (30), 2-propynyl-17alpha-methylestradiol (39), 2-ethoxy-17-(1'-methylene)estra-1,3,5(10)-triene-3-ol (50) and 2-ethoxy-17alpha-methylestradiol (51) showed similar or greater tubulin polymerization inhibition than 2-methoxyestradiol (1) and contained moieties that are expected to inhibit deactivating metabolic processes. All of the compounds tested were cytotoxic in the panel of 55 human cancer cell cultures, and generally, the derivatives that displayed the most activity against tubulin were also the most cytotoxic.
• ortho-Formylation of estrogens. Synthesis of the anti-cancer agent 2-methoxyestradiol
  作者：Øyvind W. Akselsen、Trond Vidar Hansen

  DOI：10.1016/j.tet.2011.08.005

  日期：2011.10

  Several estrogens were mono-formylated using a mixture of paraformaldehyde. MgCl2, and Et3N in refluxing THF. In all cases, the 2-isomer was formed as the major product with high regioselectivity compared to the 4-isomer. Excellent to high yields were obtained in all examples except one. The method was applied for an efficient synthesis of the anti-cancer agent 2-methoxyestradiol. (C) 2011 Elsevier Ltd. All rights reserved.