3-(tert-butyldimethylsilyloxy)-17α-(3'-hydroxyprop-1'-ynyl)estradiol | 211183-97-0

• 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
• 英文名称: 3-(tert-butyldimethylsilyloxy)-17α-(3'-hydroxyprop-1'-ynyl)estradiol
• 英文别名: 3-O-tert-butyldimethylsilyl-17α-hydroxypropargyl-β-estradiol
• CAS: 211183-97-0
• 化学式: C₂₇H₄₀O₃Si
• 分子量: 440.698
• InChiKey: OMGOFMCLFVJQGJ-IUJPGNIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  31.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  49.69
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(tert-butyldimethylsilyloxy)-17α-(3'-hydroxyprop-1'-ynyl)estradiol 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.17h， 以0.152 g的产率得到17α-(hydroxypropargyl)-3,17β-estradiol
  参考文献：
  名称：

  Novel Estradiol Derivatives Labeled with Ru, W, and Co Complexes. Influence on Hormone-Receptor Affinity of Several Organometallic Groups at the 17 Position

  摘要：

  In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17alpha position, modification of 17beta-estradiol at this position was carried out by using the organometallic groups -CdropC-(eta(5)-C5H4)RuCp, CH2-(eta(5)-C5H4)RuCp, -CdropC-(eta(5)-C5H4)-W(CO)(3)(Me), -(CdropCCHO)Co-2(CO)(6), and -(CdropCCH(2)OH)CO2(CO)(6). The relative binding affinity (RBA) values for estradiol receptor alpha showed that recognition was good (RBA between 20 and 13.5%) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced. (RBA = 1%) for a substituent such as -CH2-(eta(5)-C5H4)-RuCp, in which the spacer is reduced to a single flexible sp(3) carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular-modeling study in which 5, an organometallic hormone with a rigid spacer, or 7, a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand-Binding Domain of estrogen receptor alpha.

  DOI：

  10.1002/1521-3765(20021115)8:22<5241::aid-chem5241>3.0.co;2-m
• 作为产物：
  描述：

  叔丁基二甲硅基三氟甲磺酸酯 在 2,6-二甲基吡啶 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.5h， 生成 3-(tert-butyldimethylsilyloxy)-17α-(3'-hydroxyprop-1'-ynyl)estradiol
  参考文献：
  名称：

  选择性设计降解转录因子雌激素受体-α †的药物的分子设计，化学合成和生物学评估

  摘要：

  2-苯基喹啉（1）在无添加剂的长波长紫外光和中性条件下，在光辐照下降解了蛋白质。我们设计并合成了分别含有雌二醇和4-羟基他莫昔芬部分的2-苯基喹啉-雌激素受体-α（ER-α）激动剂（杂交2）和2-苯基喹啉-ER-α拮抗剂（杂交3）。这些2-苯基喹啉杂种有效地和选择性地光降解了目标转录因子ER-α，后者对雌二醇和4-羟基他莫昔芬具有很高的亲和力。在玻璃容器和MCF-7乳腺癌细胞中均检测了靶标选择性光降解，这取决于ER-α的生长。另外，2-苯基喹啉-雌二醇杂化物2在没有光照射的情况下，它起着ER-α激动剂的作用，促进了MCF-7的生长，而由于ER-α的光降解，它在光照射后抑制了MCF-7细胞的生长。相反，由于4-羟基他莫昔芬部分对ER-α的拮抗作用，在没有光照射的情况下，2-苯基喹啉-4-羟基他莫昔芬杂种3抑制MCF-7细胞的生长，并且在光辐照后显着抑制细胞4-羟基他莫昔芬部分的双重拮抗作用和ER-α的光降解引起细胞生长。

  DOI：

  10.1039/c1ob05629h

文献信息

• Selective nuclear receptor-targeted systems for delivery of cytotoxins to cancer cells for targeted photodynamic therapy
  申请人：——

  公开号：US20030220313A1

  公开（公告）日：2003-11-27

  An estrogen/antiestrogen-porphyrin conjugate, their composition and methods for their use are claimed. The active compounds of the invention are conjugates consisting of an estrogen or anti estrogen portion, tether or linker portion and a porphyrin portion. The method of invention exploits an active process that involves strong and specific interactions between nuclear receptor and its cognate ligand.

  一种雌激素/抗雌激素-卟啉共轭物、其组成和使用方法被声明。该发明的活性化合物是由雌激素或抗雌激素部分、连接或链节部分和卟啉部分构成的共轭物。该发明的方法利用一个涉及核受体及其同源配体之间强烈和特异相互作用的活性过程。
• Target-selective degradation of proteins by a light-activated 2-phenylquinoline-estradiol hybrid
  作者：Akane Suzuki、Kana Tsumura、Takeo Tsuzuki、Shuichi Matsumura、Kazunobu Toshima

  DOI：10.1039/b708947c

  日期：——

  A designed 2-phenylquinoline-estradiol hybrid effectively and selectively degraded the target transcription factor, human estrogen receptor-alpha (hER-alpha), which has a high affinity with the estradiol moiety, under long-wavelength UV photo-irradiation, without additives and under neutral conditions.

  设计的2-苯基喹啉-雌二醇杂合体在长波紫外光辐照下，无需添加任何添加剂，即可有效，选择性地降解与雌二醇部分具有高亲和力的目标转录因子人雌激素受体-α（hER-alpha）。在中性条件下。
• Synthesis of 17α-substituted ethynylestradiols: Potential ligands for drug vectors
  作者：Amadou R. Yaya、Mohamed Touaibia、Gassan Massarweh、Fernande D. Rochon、Livain Breau

  DOI：10.1016/j.steroids.2010.03.004

  日期：2010.7

  17 alpha-substituted ethynylestradiols, derived from estrone, were converted to their corresponding 17 alpha-(bromo- or iodo-propargyl)estrone intermediates. Nucleophilic substitution onto these moieties with malonate diester followed by hydrolysis and complexation with cis-Pt(Me(2)en)I-2 (Me(2)en = N,N-dimethylethylenediamine) gave cis-Pt(Me(2)en)(2-(3-(17 beta-estradiol-17 alpha-yl)-prop-2-ynyl)malonato) 7, thus demonstrating that these estrogen-derived compounds can be used to synthesize stable Pt(II) complexes. The 3-(17 beta-estradiol-17 alpha-yl)-prop-2-ynyl-1-sulfanylethylthiol 23 was also prepared. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.