2-(1'-ketopropyl)-17β-estradiol

• 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-(1'-ketopropyl)-17β-estradiol
• 英文别名: 1-[(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-2-yl]propan-1-one
• 化学式: C₂₁H₂₈O₃
• 分子量: 328.452
• InChiKey: ZRMDOZITMKDNBP-SNOUBDJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1'-ketopropyl)-17β-estradiol 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 为溶剂， 以97 %的产率得到
  参考文献：
  名称：

  框架整合雌二醇-苯并异恶唑嵌合体的取代多样性定向合成和体外抗癌活性

  摘要：

  类固醇和其他药效团的杂交通常会改变母体化合物的生物活性，从而提高选择性和副作用。在这项研究中，雌二醇和 3'-（未）取代的苯并异恶唑部分通过芳香环的结构整合结合成新分子。简单的雌激素原料，如雌酮、雌二醇和雌二醇-3-甲基醚用于多步转化。一些杂环衍生物是通过甲酰化或 Friedel-Crafts 酰化-肟化-环化序列从雌烷前体制备的，而其他杂环衍生物是通过官能团相互转化策略获得的。合成化合物的抗增殖活性在各种人类宫颈癌、乳腺癌和前列腺癌细胞系（HeLa、MCF-7、PC3、DU-145) 和非癌性 MRC-5 成纤维细胞。基于初级细胞毒性筛选，选择了最有效的癌症选择性化合物，它们的 IC确定了50 个值，并通过定量实时 PCR 评估了它们的凋亡诱导潜力。药理学研究揭示了强烈的结构-功能关系，其中 C-17 上带有羟基的衍生物与 17-乙酰化对应物相比表现出更强的抗癌活性。本研究得出结论，新型

  DOI：

  10.3390/molecules27217456
• 作为产物：
  描述：

  雌二醇 在 aluminum oxide 、 三甲基氯硅烷 、 sodium hydride 、 三氟乙酸酐 、 sodium iodide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 87.25h， 生成 2-(1'-ketopropyl)-17β-estradiol
  参考文献：
  名称：

  Effects of Altering the Electronics of 2-Methoxyestradiol on Cell Proliferation, on Cytotoxicity in Human Cancer Cell Cultures, and on Tubulin Polymerization

  摘要：

  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.

  DOI：

  10.1021/jm049647a

文献信息

• 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.
• Substitutional Diversity-Oriented Synthesis and In Vitro Anticancer Activity of Framework-Integrated Estradiol-Benzisoxazole Chimeras
  作者：Ferenc Kovács、Dóra Izabella Adamecz、Ferenc István Nagy、Benedek Papp、Mónika Kiricsi、Éva Frank

  DOI：10.3390/molecules27217456

  日期：——

  moieties were combined into novel molecules by structural integration of their aromatic rings. Simple estrogen starting materials, such as estrone, estradiol and estradiol-3-methylether were used for the multistep transformations. Some of the heterocyclic derivatives were prepared from the estrane precursor by a formylation or Friedel–Crafts acylation—oximation—cyclization sequence, whereas others were

  类固醇和其他药效团的杂交通常会改变母体化合物的生物活性，从而提高选择性和副作用。在这项研究中，雌二醇和 3'-（未）取代的苯并异恶唑部分通过芳香环的结构整合结合成新分子。简单的雌激素原料，如雌酮、雌二醇和雌二醇-3-甲基醚用于多步转化。一些杂环衍生物是通过甲酰化或 Friedel-Crafts 酰化-肟化-环化序列从雌烷前体制备的，而其他杂环衍生物是通过官能团相互转化策略获得的。合成化合物的抗增殖活性在各种人类宫颈癌、乳腺癌和前列腺癌细胞系（HeLa、MCF-7、PC3、DU-145) 和非癌性 MRC-5 成纤维细胞。基于初级细胞毒性筛选，选择了最有效的癌症选择性化合物，它们的 IC确定了50 个值，并通过定量实时 PCR 评估了它们的凋亡诱导潜力。药理学研究揭示了强烈的结构-功能关系，其中 C-17 上带有羟基的衍生物与 17-乙酰化对应物相比表现出更强的抗癌活性。本研究得出结论，新型