3,5-Dimethyl-4-stilbenol | 122917-30-0

• 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: 3,5-Dimethyl-4-stilbenol
• 英文别名: (E)-2,6-dimethyl-4-styrylphenol；3,5-dimethyl-4-hydroxystilbene；2,6-dimethyl-4-[(E)-2-phenylethenyl]phenol
• CAS: 122917-30-0
• 化学式: C₁₆H₁₆O
• 分子量: 224.302
• InChiKey: PAHKYLUYTGBFNW-CMDGGOBGSA-N

物化性质

• 熔点：
  139-141 °C
• 沸点：
  354.1±37.0 °C(Predicted)
• 密度：
  1.101±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,5-Dimethyl-4-stilbenol 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以91%的产率得到2.6-Dimethyl-4-phenaethyl-phenol
  参考文献：
  名称：

  Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies

  摘要：

  To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. Herein, we evaluated 40 bisaryl molecules based on 10 unique linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3). Coconsideration of amyloid inhibition and ex vivo plasma TTR binding selectivity data reveal that direct connection of the two aryls or linkage through nonpolar E-olefin or -CH 2CH 2- substructures generates the most potent and selective TTR amyloidogenesis inhibitors exhibiting minimal undesirable binding to the thyroid hormone nuclear receptor or the COX-1 enzyme. Five high-resolution TTR.inhibitor crystal structures (1.4-1.8 A) provide insight into why such linkers afford inhibitors with greater potency and selectivity.

  DOI：

  10.1021/jm800435s
• 作为产物：
  描述：

  (E)-2-methoxy-1,3-dimethyl-5-styrylbenzene 在 三溴化硼 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 2.0h， 以87%的产率得到3,5-Dimethyl-4-stilbenol
  参考文献：
  名称：

  Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies

  摘要：

  To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. Herein, we evaluated 40 bisaryl molecules based on 10 unique linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3). Coconsideration of amyloid inhibition and ex vivo plasma TTR binding selectivity data reveal that direct connection of the two aryls or linkage through nonpolar E-olefin or -CH 2CH 2- substructures generates the most potent and selective TTR amyloidogenesis inhibitors exhibiting minimal undesirable binding to the thyroid hormone nuclear receptor or the COX-1 enzyme. Five high-resolution TTR.inhibitor crystal structures (1.4-1.8 A) provide insight into why such linkers afford inhibitors with greater potency and selectivity.

  DOI：

  10.1021/jm800435s

文献信息

• Oxygenation of (E)-4-stilbenols catalysed by cobalt(II) schiff base chelates
  作者：P.A. Ganeshpure、S. Satish

  DOI：10.1016/s0040-4039(00)82415-6

  日期：1988.1

  Cobalt(II) Schiff base chelate, CoSMDPT (1), catalysed 'the oxygenation of (E)-4-stilbenols (2a–2d), to give two molecules of aldehydes. Both the oxygen atoms of dioxygen are incorporated into the substrate, providing a good chemical model for dioxygenase reactions.

  钴（II）席夫碱螯合物CoSMDPT（1）催化（E）-4-芪苯酚（2a–2d）的氧合，得到两个醛分子。双氧的两个氧原子都结合到底物中，为双氧酶反应提供了良好的化学模型。
• 一种取代二芳基嘧啶类衍生物及其制备方法 与应用
  申请人：山东大学

  公开号：CN106831605B

  公开（公告）日：2019-07-05

  本发明公开了一种二芳基嘧啶衍生物及其制备方法和应用。所述取代二芳基嘧啶衍生物或其药学上可接受的盐或前药，具有如下通式I或II所示的结构，本发明还包括取代二芳基嘧啶衍生物的制备方法以及含有一个或多个此类化合物的组合物在制备治疗和预防人免疫缺陷病毒(HIV)药物中的应用。
• Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored “hydrophobic channel”
  作者：Zhongxia Zhou、Tao Liu、Dongwei Kang、Zhipeng Huo、Gaochan Wu、Dirk Daelemans、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu

  DOI：10.1039/c7ob02828h

  日期：——

  We described the identification of novel HIV-1 NNRTIs via exploration of the chemical space of a seldom explored “hydrophobic channel”.

  我们通过探索很少被探索的“疏水通道”的化学空间，描述了新型HIV-1 NNRTIs的鉴定。
• SMALL MOLECULES THAT COVALENTLY MODIFY TRANSTHYRETIN
  申请人：Kelly Jeffery W.

  公开号：US20120270938A1

  公开（公告）日：2012-10-25

  A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

  本文介绍了一类共价动力稳定剂化合物家族，它们选择性地、共价地与突出的血浆蛋白转甲状腺素结合，而不是其他4000多种人类血浆蛋白。一种可考虑的化合物对应于以下的结构式I，其中各取代基在内部定义，并与转甲状腺素四聚体中的一个或两个Lys-15 ε-氨基基团发生化学选择性反应。晶体结构证实了化合物亚结构和结合酰胺键的结合方向。与非共价对应物相比，共价转甲状腺素动力稳定剂表现出优越的淀粉样抑制效能，并抑制与淀粉样生成相关的细胞毒性。
• Small Molecules That Covalently Modify Transthyretin
  申请人：Kelly Jeffery W.

  公开号：US20140336254A1

  公开（公告）日：2014-11-13

  A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

  本发明揭示了一种共价动力稳定剂化合物家族，它们选择性地和共价地与显著的血浆蛋白转甲状腺素反应，而不是其他4000多种人类血浆蛋白。考虑到的化合物对应于以下公式I的结构，其中各种取代基在内部定义，并与转甲状腺素四聚体内的四个Lys-15 ε-氨基基团之一或两个发生化学选择性反应。晶体结构证实了化合物亚结构和结合酰胺键的结合方向。与非共价对应物相比，共价转甲状腺素动力稳定剂表现出优越的淀粉样抑制效力，并抑制与淀粉样生成相关的细胞毒性。