(dibenzofuran-1-yloxy)triisopropylsilane | 853070-69-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (dibenzofuran-1-yloxy)triisopropylsilane
• 英文别名: Dibenzofuran-1-yloxy-tri(propan-2-yl)silane
• CAS: 853070-69-6
• 化学式: C₂₁H₂₈O₂Si
• 分子量: 340.538
• InChiKey: ZUHYLRGVCSWTJG-UHFFFAOYSA-N

物化性质

• 沸点：
  398.5±15.0 °C(Predicted)
• 密度：
  1.021±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.14
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  22.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (dibenzofuran-1-yloxy)triisopropylsilane 在 吡啶 、 四甲基乙二胺 、 palladium dibenzylidene acetone 、 四丁基氟化铵 、 仲丁基锂 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 环己烷 、 甲苯 、 苯 为溶剂， 反应 37.5h， 生成 1-phenylaminodibenzofuran-4,6-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Potent and Selective Structure-Based Dibenzofuran Inhibitors of Transthyretin Amyloidogenesis:  Kinetic Stabilization of the Native State

  摘要：

  Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation and partial monomer denaturation to produce a misassembly competent species. This process has been followed by turbidity to identify transthyretin amyloidogenesis inhibitors including dibenzofuran-4,6-dicarboxylic acid (1). An X-ray cocrystal structure of TTR.1(2) reveals that it only utilizes the outer portion of the two thyroxine binding pockets to bind to and inhibit TTR amyloidogenesis. Herein, structure-based design was employed to append aryl substituents at C1 of the dibenzofuran ring to complement the unused inner portion of the thyroxine binding pockets. Twenty-eight amyloidogenesis inhibitors of increased potency and dramatically increased plasma TTR binding selectivity resulted. These function by imposing kinetic stabilization on the native tetrameric structure of TTR, creating a barrier that is insurmountable under physiological conditions. Since kinetic stabilization of the TTR native state by interallelic trans suppression is known to ameliorate disease, there is reason to be optimistic that the dibenzofuran-based inhibitors will do the same. Preventing the onset of amyloidogenesis is the most conservative strategy to intervene clinically, as it remains unclear which of the TTR misassembly intermediates results in toxicity. The exceptional binding selectivity enables these inhibitors to occupy the thyroxine binding site(s) in a complex biological fluid such as blood plasma, required for inhibition of amyloidogenesis in humans. It is now established that the dibenzofuran-based amyloidogenesis inhibitors have high selectivity, affinity, and efficacy and are thus excellent candidates for further pharmacologic evaluation.

  DOI：

  10.1021/ja044351f
• 作为产物：
  描述：

  9b-Bromo-2,4,6,8-tetra-tert-butyl-9bH-dibenzofuran-1-one 在 4-二甲氨基吡啶 、 三氯化铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (dibenzofuran-1-yloxy)triisopropylsilane
  参考文献：
  名称：

  Potent and Selective Structure-Based Dibenzofuran Inhibitors of Transthyretin Amyloidogenesis:  Kinetic Stabilization of the Native State

  摘要：

  Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation and partial monomer denaturation to produce a misassembly competent species. This process has been followed by turbidity to identify transthyretin amyloidogenesis inhibitors including dibenzofuran-4,6-dicarboxylic acid (1). An X-ray cocrystal structure of TTR.1(2) reveals that it only utilizes the outer portion of the two thyroxine binding pockets to bind to and inhibit TTR amyloidogenesis. Herein, structure-based design was employed to append aryl substituents at C1 of the dibenzofuran ring to complement the unused inner portion of the thyroxine binding pockets. Twenty-eight amyloidogenesis inhibitors of increased potency and dramatically increased plasma TTR binding selectivity resulted. These function by imposing kinetic stabilization on the native tetrameric structure of TTR, creating a barrier that is insurmountable under physiological conditions. Since kinetic stabilization of the TTR native state by interallelic trans suppression is known to ameliorate disease, there is reason to be optimistic that the dibenzofuran-based inhibitors will do the same. Preventing the onset of amyloidogenesis is the most conservative strategy to intervene clinically, as it remains unclear which of the TTR misassembly intermediates results in toxicity. The exceptional binding selectivity enables these inhibitors to occupy the thyroxine binding site(s) in a complex biological fluid such as blood plasma, required for inhibition of amyloidogenesis in humans. It is now established that the dibenzofuran-based amyloidogenesis inhibitors have high selectivity, affinity, and efficacy and are thus excellent candidates for further pharmacologic evaluation.

  DOI：

  10.1021/ja044351f

文献信息

• Rapid Access to Bi- and Tri-Functionalized Dibenzofurans and their Application in Selective Suzuki-Miyaura Cross Coupling Reactions
  作者：Caroline Wern、Christian Ehrenreich、Dominik Joosten、Thorsten vom Stein、Herwig Buchholz、Burkhard König

  DOI：10.1002/ejoc.201801286

  日期：2018.11.8

  Syntheses of 1,2-, 1,3-, 1,4-, 1,8-, 2,4-, 3,4-, 4,8-, 1,2,4-, 1,2,8- and 1,3,4-functionalized dibenzofurans in few steps with good to excellent yields starting from dibenzofuran-1-ol or -4-ol are presented. These rapidly accessible bi- or tri-functionalized building blocks are of great interest for the synthesis of bioactive substances or functional material development. Furthermore, for intermediates

  1,2-, 1,3-, 1,4-, 1,8-, 2,4-, 3,4-, 4,8-, 1,2,4-, 1,2,8-的合成和 1,3,4-官能化的二苯并呋喃在几个步骤中以从二苯并呋喃-1-醇或-4-醇开始的良好到优异的产率呈现。这些可快速获取的双或三功能化构建块对于生物活性物质的合成或功能材料的开发具有重要意义。此外，对于包含溴和三氟甲磺酸酯部分的中间体，描述了通过 Suzuki-Miyaura 反应 (SMR) 的选择性单取代。
• [EN] MATERIALS FOR ORGANIC ELECTROLUMINESCENT DEVICES<br/>[FR] MATÉRIAUX POUR DISPOSITIFS ÉLECTROLUMINESCENTS ORGANIQUES
  申请人：MERCK PATENT GMBH

  公开号：WO2019170578A1

  公开（公告）日：2019-09-12

  The present invention relates to compounds of the formula (1) which are suitable for use in electronic devices, in particular organic electroluminescent devices, and to electronic devices which comprise these compounds.

  本发明涉及适用于电子设备，特别是有机电致发光器件的化合物（1）的公式，以及包含这些化合物的电子设备。
• Transthyretin stabilization
  申请人：Kelly W. Jeffery

  公开号：US20050261365A1

  公开（公告）日：2005-11-24

  Dibenzofuran-4,6-dicarboxylic acid core structures having an aromatic substituent appended onto the at the C1 position using three different types of linkages are disclosed herein and shown to afford exceptional amyloidogenesis inhibitors that display increased affinity and greatly increased binding selectivity to TTR over all the other plasma proteins, relative to lead compound 1. It is further disclosed herein that these compounds function by imposing kinetic stabilization on the TTR tetramer.

  本文披露了具有芳香族取代基的二苯并呋喃-4,6-二羧酸核结构，该取代基附加在C1位置上，使用三种不同类型的连接，显示出优异的淀粉样生成抑制剂，这些抑制剂显示出相对于引物化合物1，具有更高的亲和力和大大增加的结合选择性，相对于所有其他血浆蛋白。进一步披露了这些化合物通过对TTR四聚体施加动力学稳定来发挥作用。