2-tert-butyl-1-methoxy-4-[(E)-2-(4-methoxyphenyl)ethenyl]benzene | 945484-69-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 2-tert-butyl-1-methoxy-4-[(E)-2-(4-methoxyphenyl)ethenyl]benzene
• CAS: 945484-69-5
• 化学式: C₂₀H₂₄O₂
• 分子量: 296.409
• InChiKey: SCMNPPJQEPXJDO-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.17
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  18.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2-tert-butyl-1-methoxy-4-[(E)-2-(4-methoxyphenyl)ethenyl]benzene 在 甲基碘化镁 、 氯化铵 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 2-tert-butyl-4-[(E)-2-(4-hydroxyphenyl)ethenyl]phenol
  参考文献：
  名称：

  具有神经保护活性并且不干扰雌激素和芳烃受体介导的转录的新型羟基二苯乙烯类衍生物

  摘要：

  我们合成了一系列新的（E）二苯乙烯类衍生物，其在与反式-白藜芦醇的环位置相同或相似的环位置上含有羟基，并带有一个或两个与4'-OH邻位的给电子基团，我们已经使用它们评估了它们的神经保护活性。谷氨酸攻击的HT22海马神经元可模拟氧化应激诱导的神经元细胞死亡。活性最高的衍生物5-{（E）-2- [3,5-双（1-乙基丙基）-4-羟苯基]乙烯基} -1,3-苯二醇（2），5-[（E）-2 -（（3,5-二叔丁基-4-羟基苯基乙烯基）]-1,3-苯二醇（4）和5-{（1 E，3 E）-4- [3,5-双（1-乙基丙基）-4-羟基苯基] -1,3-丁二烯基} -1,3-苯二醇（6）的EC 50值分别为30、45和12 nM。 ，并且是。效力比白藜芦醇高100到400倍。衍生物2，4和6缺乏细胞毒性活性对HT22细胞和雌激素反应元件依赖性基因表达雌激素受体激动剂或拮抗剂活性，并在MCF-7人乳腺癌细胞

  DOI：

  10.1016/j.bmc.2010.11.018
• 作为产物：
  描述：

  4-(Bromomethyl)-2-tert-butyl-1-methoxybenzene 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 2-tert-butyl-1-methoxy-4-[(E)-2-(4-methoxyphenyl)ethenyl]benzene
  参考文献：
  名称：

  Engineered Chimeric Enzymes as Tools for Drug Discovery:  Generating Reliable Bacterial Screens for the Detection, Discovery, and Assessment of Estrogen Receptor Modulators

  摘要：

  Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.

  DOI：

  10.1021/ja067754j