(17beta)-3,17-二(甲氧基甲氧基)雌甾-1(10),2,4-三烯-2-甲醛 | 123715-80-0

• 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-甲醛
• 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]phenanthrene-2-carbaldehyde
• 英文别名: 2-formyl-3,17β-O,O-bis(methoxymethyl)estradiol；2-formyl-3,17-β-O-bis(methoxymethyl)estradiol；2-formyl-3,17β-O-bis(methoxymethyl)estradiol；3,17β-bis(methoxymethoxy)estra-1,3,5(10)-triene-2-carbaldehyde；2-Formyl-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]phenanthrene-2-carbaldehyde
• CAS: 123715-80-0
• 化学式: C₂₃H₃₂O₅
• 分子量: 388.504
• InChiKey: PGRCGHQMTWFDPC-PAHONEIHSA-N

物化性质

• 沸点：
  508.1±50.0 °C(Predicted)
• 密度：
  1.16±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)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  54
• 氢给体数：
  0
• 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-甲醛 在 盐酸 、 sodium phosphate dibasic dodecahydrate 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.17h， 生成 2-甲氧基雌二醇
  参考文献：
  名称：

  ortho-Formylation of estrogens. Synthesis of the anti-cancer agent 2-methoxyestradiol

  摘要：

  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.

  DOI：

  10.1016/j.tet.2011.08.005
• 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 13.5h， 生成 (17beta)-3,17-二(甲氧基甲氧基)雌甾-1(10),2,4-三烯-2-甲醛
  参考文献：
  名称：

  2-甲氧基雌二醇和类似物作为新型抗增殖剂：分析DNA合成抑制和雌激素受体结合的三维定量结构-活性关系。

  摘要：

  2-甲氧基雌二醇（2-MEO）是雌激素的代谢产物，是开发新型抗肿瘤和抗炎药的引人注目的先导化合物，因为它在一个分子中体现了抗增殖和抗血管生成的活性。但是，2-MEO对雌激素受体的亲和力将导致不良的副作用。作为设计具有最佳活性谱的2-MEO样化合物的前奏，我们分析了2-MEO和一系列类似物引起G（1）细胞周期停滞的能力（通过测量DNA合成的抑制作用）人类培养的气道平滑肌）并抑制[（3）H]雌二醇与雌激素受体的结合（ER；来自大鼠子宫平滑肌）。鉴定出一种化合物，即二乙酰氧基烯二醇衍生物，具有合理的DNA合成能力（pIC（50）= 5。97），但对ER的亲和力却微不足道（pIC（50）<5）。使用比较分子场分析（CoMFA）技术，为这些活性建立了三维定量结构-活性关系。优化的CoMFA模型的比较揭示了DNA合成抑制和ER结合的独特结构要求。例如，在类固醇A环平面下方的2位上通过正电取代增强了DN

  DOI：

  10.1124/mol.61.5.1053

文献信息

• Synthesis of 2-[11C]methoxy-3,17β-O,O-bis(sulfamoyl)estradiol as a new potential PET agent for imaging of steroid sulfatase (STS) in cancers
  作者：Min Wang、Lu Xu、Mingzhang Gao、Kathy D. Miller、George W. Sledge、Qi-Huang Zheng

  DOI：10.1016/j.steroids.2012.04.007

  日期：2012.7

  design and synthesis of 2-[(11)C]methoxy-3,17β-O,O-bis(sulfamoyl)estradiol ([(11)C]5) as a new potential imaging agent for biomedical imaging technique positron emission tomography (PET) to image STS in cancers. The authentic standard 5 was synthesized from 17β-estradiol by published procedures in 5 steps with 40% overall chemical yield. The precursor 2-hydroxy-3,17β-O,O-bis(sulfamoyl)estradiol (14a) for

  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
• 2-(Hydroxyalkyl)estradiols:  Synthesis and Biological Evaluation
  作者：Carl J. Lovely、Nancy E. Gilbert、Muriel M. Liberto、Damon W. Sharp、Young C. Lin、Robert W. Brueggemeier

  DOI：10.1021/jm9508245

  日期：1996.1.1

  Synthetic estrogens possessing hydroxyalkyl side chains at the C-2 position of the A-ring were designed in order to further elucidate the structural and electronic requirements of the estrogen receptor to A-ring modifications. Furthermore, these compounds were envisaged as being stable analogs of the estradiol metabolite 2-hydroxyestradiol. The homologous series of 2-(hydroxyalkyl)estradiols 1-3 has

  为了进一步阐明雌激素受体对A环修饰的结构和电子要求，设计了在A环的C-2位置具有羟烷基侧链的合成雌激素。此外，设想这些化合物是雌二醇代谢物2-羟基雌二醇的稳定类似物。通过2-甲酰基雌二醇6的扩链来制备2-（羟烷基）雌二醇1-3的同源系列，所述2-甲酰基雌二醇6是通过雌二醇的邻位甲硅烷基化制备的。测定取代的雌二醇1-3与MCF-7细胞中的雌激素受体结合并诱导雌激素反应性基因表达的能力。雌二醇同系物对MCF-7细胞雌激素受体的亲和力比雌二醇弱得多，相对结合亲和力（雌二醇= 100）的范围从2-（羟甲基）雌二醇（1）的1.11到2-（羟丙基）雌二醇（3）的0.073。雌二醇同源物对pS2基因的mRNA诱导的相对活性与MCF-7细胞中雌激素受体的相对结合亲和力非常相似。2-（羟甲基）-雌二醇显示出与邻苯二酚雌激素2-羟基雌二醇相似的雌激素受体亲和力和pS2基因诱导作用，并且可能被证明可用于检查2-羟基雌激素同系物的进一步生物学效应。
• 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.
• Park; Choe; Chi, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S432-S433
  作者：Park、Choe、Chi、Choi、Lee、Kim、Kim

  DOI：——

  日期：——