3-(tert-butyldimethylsilyloxy)-17α-trimethylsilylethynyl-β-estradiol | 346700-38-7

• 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
• 英文名称: 3-(tert-butyldimethylsilyloxy)-17α-trimethylsilylethynyl-β-estradiol
• 英文别名: 3-tertbutyldimethylsilyloxy-17α-trimethylsilylethynyl-β-estradiol；(8R,9S,13S,14S,17S)-3-[tert-butyl(dimethyl)silyl]oxy-13-methyl-17-(2-trimethylsilylethynyl)-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol
• CAS: 346700-38-7
• 化学式: C₂₉H₄₆O₂Si₂
• 分子量: 482.854
• InChiKey: GBXNZLJLCCEOHN-WXJBELMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.54
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(tert-butyldimethylsilyloxy)-17α-trimethylsilylethynyl-β-estradiol 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 3-(tert-butyldimethylsiloxy)-17α-ethynylestradiol
  参考文献：
  名称：

  Triazole-estradiol analogs: A potential cancer therapeutic targeting ovarian and colorectal cancer

  摘要：

  1,2,3-triazoles have continuously shown effectiveness as biologically active systems towards various cancers, and when used in combination with steroid skeletons as a carrier, which can act as a drug delivery system, allows for a creation of a novel set of analogs that may be useful as a pharmacophore leading to a potential treatment option for cancer. A common molecular target for cancer inhibition is that of the Epidermal Growth Factor Receptor/Mitogen Activated Protein Kinase pathways, as inhibition of these proteins is associated with a decrease in cell viability. Estradiol-Triazole analogs were thus designed using a molecular modeling approach. Thirteen of the high scoring analogs were then synthesized and tested in-vitro on an ovarian cancer cell line (A2780) and colorectal cancer cell line (HT-29). The most active compound, Fz25, shows low micromolar activity in both the ovarian (15.29 ± 2.19 µM) and colorectal lines (15.98 ± 0.39 µM). Mechanism of action studies proved that Fz25 moderately arrests cells in the G1 phase of the cell cycle, specifically inhibiting STAT3 in both cell lines. Additionally, Fz57 shows activity in the colorectal line (24.19 ± 1.37 µM). Inhibition studies in both cell lines show inhibition against various proteins in the EGFR pathway, namely EGFR, STAT3, ERK, and mTOR. To further study their effects as therapeutics, Fz25 and Fz57 were studied against drug efflux proteins, which are associated with drug resistance, and were found to inhibit the ABC transporter P-glycoprotein. We can conclude that these estradiol-triazole analogs provide a key for future studies targeting protein inhibition and drug resistance in cancer.

  DOI：

  10.1016/j.steroids.2021.108950
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 在 咪唑 、 叔丁基锂 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-(tert-butyldimethylsilyloxy)-17α-trimethylsilylethynyl-β-estradiol
  参考文献：
  名称：

  Triazole-estradiol analogs: A potential cancer therapeutic targeting ovarian and colorectal cancer

  摘要：

  1,2,3-triazoles have continuously shown effectiveness as biologically active systems towards various cancers, and when used in combination with steroid skeletons as a carrier, which can act as a drug delivery system, allows for a creation of a novel set of analogs that may be useful as a pharmacophore leading to a potential treatment option for cancer. A common molecular target for cancer inhibition is that of the Epidermal Growth Factor Receptor/Mitogen Activated Protein Kinase pathways, as inhibition of these proteins is associated with a decrease in cell viability. Estradiol-Triazole analogs were thus designed using a molecular modeling approach. Thirteen of the high scoring analogs were then synthesized and tested in-vitro on an ovarian cancer cell line (A2780) and colorectal cancer cell line (HT-29). The most active compound, Fz25, shows low micromolar activity in both the ovarian (15.29 ± 2.19 µM) and colorectal lines (15.98 ± 0.39 µM). Mechanism of action studies proved that Fz25 moderately arrests cells in the G1 phase of the cell cycle, specifically inhibiting STAT3 in both cell lines. Additionally, Fz57 shows activity in the colorectal line (24.19 ± 1.37 µM). Inhibition studies in both cell lines show inhibition against various proteins in the EGFR pathway, namely EGFR, STAT3, ERK, and mTOR. To further study their effects as therapeutics, Fz25 and Fz57 were studied against drug efflux proteins, which are associated with drug resistance, and were found to inhibit the ABC transporter P-glycoprotein. We can conclude that these estradiol-triazole analogs provide a key for future studies targeting protein inhibition and drug resistance in cancer.

  DOI：

  10.1016/j.steroids.2021.108950

文献信息

• Utilizing Estra-1,3,5,16-Tetraene Scaffold: Design and Synthesis of Nitric Oxide Donors as Chemotherapeutic Resistance Combating Agents in Liver Cancer
  作者：Mahrous A. Abou-Salim、Mohamed A. Shaaban、Mohammed K. Abd El Hameid、Mohammed M. Alanazi、Fathi Halaweish、Yaseen A. M. M. Elshaier

  DOI：10.3390/molecules28062754

  日期：——

  A new series of nitric oxide-releasing estra-1,3,5,16-tetraene analogs (NO-∆-16-CIEAs) was designed and synthesized as dual inhibitors for EGFR and MRP2 based on our previous findings on estra-1,3,5-triene analog NO-CIEA 17 against both HepG2 and HepG2-R cell lines. Among the target compounds, 14a (R-isomer) and 14b (S-isomer) displayed potent anti-proliferative activity against both HepG2 and HepG2-R

  基于我们之前对 estra-1 的研究结果，设计并合成了一系列新的释放一氧化氮的 estra-1,3,5,16-四烯类似物 (NO-Δ-16-CIEAs) 作为 EGFR 和 MRP2 的双重抑制剂， 3,5-三烯类似物 NO-CIEA 17 针对 HepG2 和 HepG2-R 细胞系。在目标化合物中，与参比药物厄洛替尼相比，14a（R-异构体）和 14b（S-异构体）对 HepG2 和 HepG2-R 细胞系均显示出有效的抗增殖活性。值得注意的是，化合物 14a 在浓度为 1.20 µM 时导致 EGFR 磷酸化显着降低，对 MEK1/2 和 ERK1/2 的磷酸化具有轻微活性。它还以剂量依赖性方式抑制 MRP2 表达，抑制率为 24%，并使细胞停滞在细胞周期的 S 期。有趣的是，与先导雌三烯类似物相比，化合物 14a（雌四烯核心）对 HepG2 和 HepG2-R 的抗增殖活性增加了两倍，证明了设计的
• Synthesis and Protein Degradation Capacity of Photoactivated Enediynes
  作者：Farid S. Fouad、Justin M. Wright、Gary Plourde II,、Ajay D. Purohit、Justin K. Wyatt、Ahmed El-Shafey、George Hynd、Curtis F. Crasto、Yiqing Lin、Graham B. Jones

  DOI：10.1021/jo051403q

  日期：2005.11.1

  The viability of proteins as targets of thermally and photoactivated enediynes has been confirmed at the molecular level. Model studies using a labeled substrate confirmed the efficacy of atom transfer from diyl radicals produced from enediynes to form captodatively stabilized carbon centered aminoacyl radicals, which then undergo either fragmentation or dimerization. To exploit this finding, a family of enediynes was developed using an intramolecular coupling strategy. Derivatives were prepared and used to target specific proteins, showing good correlation between affinity and photoinduced protein degrading activity. The findings have potential applications in the design of artificial chemical proteases and add to our understanding of the mechanism of action of the clinically important enediyne antitumor antibiotics.
• Target-Directed Enediynes:  Designed Estramycins
  作者：Graham B. Jones、George Hynd、Justin M. Wright、Ajay Purohit、Gary W. Plourde、Robert S. Huber、Jude E. Mathews、Aiwen Li、Michael W. Kilgore、Glenn J. Bubley、Molly Yancisin、Myles A. Brown

  DOI：10.1021/jo0055842

  日期：2001.6.1

  The goal of selective targeting of enediyne cytotoxins has been investigated using estrogenic delivery vehicles. A series of estrogen-enediyne conjugates were assembled, and affinity for human estrogen receptor [hERalpha] was determined. The most promising candidate induced receptor degradation following Bergman cycloaromatization and caused inhibition of estrogen-induced transcription in T47-D human breast cancer cells.