16α-[11-iodo-3,6,9-trioxaundecanyl]-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)-1,3,5(10)-estratrien-17-one | 1028357-74-5

• 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: 16α-[11-iodo-3,6,9-trioxaundecanyl]-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)-1,3,5(10)-estratrien-17-one
• CAS: 1028357-74-5
• 化学式: C₃₃H₄₇IO₈
• 分子量: 698.636
• InChiKey: MKEFEWATZPLAGB-ZZNXQXLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.66
• 重原子数：
  42.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  89.52
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  16α-[11-iodo-3,6,9-trioxaundecanyl]-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)-1,3,5(10)-estratrien-17-one 在 锂硼氢 、 4-甲基苯磺酸吡啶 作用下， 以 甲醇 、 乙醚 、 乙醇 为溶剂， 反应 20.0h， 生成 (8R,9S,13S,14S,16S,17R)-16-(hydroxymethyl)-13-methyl-16-[2-[2-[2-[2-(2-pyridin-2-ylethylamino)ethoxy]ethoxy]ethoxy]ethyl]-7,8,9,11,12,14,15,17-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol
  参考文献：
  名称：

  Design, synthesis and biological evaluation of estradiol-PEG-linked platinum(II) hybrid molecules: Comparative molecular modeling study of three distinct families of hybrids

  摘要：

  The synthesis of a series of 17 beta-estradiol-platinum(II) hybrid molecules is reported. The hybrids are made of a PEG linking chain of various length and a 2-(2'-aminoethyl)pyridine ligand. They are prepared from estrone in only 5 chemical steps with an overall yield of 22%. The length of the PEG chain does not influence the solubility of the compounds as it remains relatively constant throughout the series. MTT assays showed that the derivative with the longest PEG chain showed the best activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231). The novel PEG-hybrids are also compared in terms of activities with two other families of 17 beta-estradiol-platinum(II) hybrids that we reported in previous studies. Molecular modeling study performed on a representative member of each family of hybrids reveals distinct molecular interactions with the estrogen receptor alpha which further corroborates their notably contrasting cytocidal activities on breast cancer cell lines. This study also shows that lipophilicity and the orientation of the tether chain between the estrogenic portion and the platinum(II) core contribute markedly to the biological activity of the various families of hybrids. The most active hybrids are those possessing an alkyl tether chain at position 16 beta of the steroid nucleus. For example. derivative 3 (p = 6) is about 16 times more potent on MCF-7 breast cancer cells than the corresponding 16 alpha-PEG-hybrids (2b) made in this study. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.09.004
• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 在 4-甲基苯磺酸吡啶 、 potassium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 34.0h， 生成 16α-[11-iodo-3,6,9-trioxaundecanyl]-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)-1,3,5(10)-estratrien-17-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of estradiol-PEG-linked platinum(II) hybrid molecules: Comparative molecular modeling study of three distinct families of hybrids

  摘要：

  The synthesis of a series of 17 beta-estradiol-platinum(II) hybrid molecules is reported. The hybrids are made of a PEG linking chain of various length and a 2-(2'-aminoethyl)pyridine ligand. They are prepared from estrone in only 5 chemical steps with an overall yield of 22%. The length of the PEG chain does not influence the solubility of the compounds as it remains relatively constant throughout the series. MTT assays showed that the derivative with the longest PEG chain showed the best activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231). The novel PEG-hybrids are also compared in terms of activities with two other families of 17 beta-estradiol-platinum(II) hybrids that we reported in previous studies. Molecular modeling study performed on a representative member of each family of hybrids reveals distinct molecular interactions with the estrogen receptor alpha which further corroborates their notably contrasting cytocidal activities on breast cancer cell lines. This study also shows that lipophilicity and the orientation of the tether chain between the estrogenic portion and the platinum(II) core contribute markedly to the biological activity of the various families of hybrids. The most active hybrids are those possessing an alkyl tether chain at position 16 beta of the steroid nucleus. For example. derivative 3 (p = 6) is about 16 times more potent on MCF-7 breast cancer cells than the corresponding 16 alpha-PEG-hybrids (2b) made in this study. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.09.004

文献信息

• Synthesis of 17β-estradiol-platinum(II) hybrid molecules showing cytotoxic activity on breast cancer cell lines
  作者：Josée Provencher-Mandeville、Caroline Descôteaux、Sanat K. Mandal、Valérie Leblanc、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.bmcl.2008.03.005

  日期：2008.4

  The synthesis of a series of 17 beta-estradiol-platinum(II) hybrid molecules is reported. The hybrids are made of a PEG linking chain of various length and a 2-(2'-aminoethyl) pyridine ligand. They are prepared from estrone in five chemical steps with an overall yield of 22%. The length of the PEG chain does not influence the solubility of the compounds as it remains relatively constant throughout the series. MTT assays showed that the derivative with the longest PEG chain showed the best activity against breast cancer cell lines (MCF-7 and MDA-MB-231). Molecular modeling study rationalized the results. (C) 2008 Elsevier Ltd. All rights reserved.