4,4'-(dibutylsilanediyl)bis(2-methylphenol) | 1446215-31-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4,4'-(dibutylsilanediyl)bis(2-methylphenol)
• 英文别名: 4-[Dibutyl-(4-hydroxy-3-methylphenyl)silyl]-2-methylphenol；4-[dibutyl-(4-hydroxy-3-methylphenyl)silyl]-2-methylphenol
• CAS: 1446215-31-1
• 化学式: C₂₂H₃₂O₂Si
• 分子量: 356.58
• InChiKey: OPTVZQBIXJWQAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.88
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,4'-(dibutylsilanediyl)bis(2-methylphenol) 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 3.0h， 以33.8%的产率得到(dibutylsilanediyl)bis(2-methyl-4,1-phenylene) bis(sulfamate)
  参考文献：
  名称：

  具有前雌激素拮抗特性的含硅甾族硫酸酯酶抑制剂的设计与合成

  摘要：

  甾族硫酸酯酶（STS）是治疗绝经后激素依赖性乳腺癌的潜在靶标。已经报道了几种类固醇STS抑制剂，但是类固醇化合物难以优化并且可能与其他靶标相互作用。另一方面，我们已经证明二苯甲烷（DPM）衍生物充当雌激素受体（ER）激动剂和拮抗剂。在这里，我们旨在设计和合成非甾体DPM型STS抑制剂，它们也可以用作促雌激素拮抗剂，在被STS水解后释放具有ERα拮抗活性的代谢产物。我们合成了一系列化合物，并通过STS抑制活性测定和ER报告基因测定评估了它们的生物学活性。其中，含硅化合物16a表现出较强的STS抑制活性（IC50  = 0.17μM）。此外，其推定的代谢产物（12a）表现出有效的ERα拮抗活性（IC 50  = 29.7 nM）。

  DOI：

  10.1016/j.bmc.2014.02.025
• 作为产物：
  描述：

  邻甲酚 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 4,4'-(dibutylsilanediyl)bis(2-methylphenol)
  参考文献：
  名称：

  Structure–activity relationships of bisphenol A analogs at estrogen receptors (ERs): Discovery of an ERα-selective antagonist

  摘要：

  Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ER alpha/ER beta subtype selectivity. Among the compounds examined, 18 was found to be a potent ER alpha-antagonist with high selectivity over ER beta and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ER alpha. ER alpha-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.067

文献信息

• Structure–activity relationships of bisphenol A analogs at estrogen receptors (ERs): Discovery of an ERα-selective antagonist
  作者：Keisuke Maruyama、Masaharu Nakamura、Shusuke Tomoshige、Kazuyuki Sugita、Makoto Makishima、Yuichi Hashimoto、Minoru Ishikawa

  DOI：10.1016/j.bmcl.2013.05.067

  日期：2013.7

  Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ER alpha/ER beta subtype selectivity. Among the compounds examined, 18 was found to be a potent ER alpha-antagonist with high selectivity over ER beta and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ER alpha. ER alpha-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. (C) 2013 Elsevier Ltd. All rights reserved.
• Design and synthesis of silicon-containing steroid sulfatase inhibitors possessing pro-estrogen antagonistic character
  作者：Daisuke Kajita、Masaharu Nakamura、Yotaro Matsumoto、Makoto Makishima、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2014.02.025

  日期：2014.4

  Here, we aimed to design and synthesize non-steroidal DPM-type STS inhibitors that would also serve as pro-estrogen antagonists, releasing a metabolite with ERα-antagonistic activity upon hydrolysis by STS. We synthesized a series of compounds and evaluated their biological activities by means of STS-inhibitory activity assay and ER reporter gene assay. Among them, silicon-containing compound 16a showed

  甾族硫酸酯酶（STS）是治疗绝经后激素依赖性乳腺癌的潜在靶标。已经报道了几种类固醇STS抑制剂，但是类固醇化合物难以优化并且可能与其他靶标相互作用。另一方面，我们已经证明二苯甲烷（DPM）衍生物充当雌激素受体（ER）激动剂和拮抗剂。在这里，我们旨在设计和合成非甾体DPM型STS抑制剂，它们也可以用作促雌激素拮抗剂，在被STS水解后释放具有ERα拮抗活性的代谢产物。我们合成了一系列化合物，并通过STS抑制活性测定和ER报告基因测定评估了它们的生物学活性。其中，含硅化合物16a表现出较强的STS抑制活性（IC50  = 0.17μM）。此外，其推定的代谢产物（12a）表现出有效的ERα拮抗活性（IC 50  = 29.7 nM）。