2-(3,5-dichloro-4-(2-(2-(2-(3-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-5-yl)thioureido)ethoxy)ethoxy)ethoxy)phenylamino)benzoic acid | 1346597-65-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-(3,5-dichloro-4-(2-(2-(2-(3-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-5-yl)thioureido)ethoxy)ethoxy)ethoxy)phenylamino)benzoic acid
• 英文别名: 2-[3,5-dichloro-4-[2-[2-[2-[(3',6'-dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)carbamothioylamino]ethoxy]ethoxy]ethoxy]anilino]benzoic acid
• CAS: 1346597-65-6
• 化学式: C₄₀H₃₃Cl₂N₃O₁₀S
• 分子量: 818.688
• InChiKey: MMJKDGSPMZTYNV-UHFFFAOYSA-N

物化性质

• 沸点：
  976.9±75.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  56
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-[2-(2-T-BOC-氨基乙氧基)乙氧基]乙醇 在 N,N-二异丙基乙胺 、 三苯基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.0h， 生成 2-(3,5-dichloro-4-(2-(2-(2-(3-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-5-yl)thioureido)ethoxy)ethoxy)ethoxy)phenylamino)benzoic acid
  参考文献：
  名称：

  [EN] IDENTIFICATION OF STABILIZERS OF MULTIMERIC PROTEINS
  [FR] IDENTIFICATION DE STABILISANTS DE PROTÉINES MULTIMÉRIQUES

  摘要：

  本文披露了一些化合物及其组合物，可用于增加TTR四聚体的稳定性，减少其错误折叠和形成聚集物的倾向。本文还提供了使用这些化合物和组合物来增加TTR稳定性并从而减少TTR聚集物形成的方法。本文还披露了用于筛选增加TTR稳定性的候选化合物的方法。本文还披露了一种包括TTR结合化合物通过连接物连接到靶向基团的异双功能化合物，用于破坏靶蛋白的蛋白-蛋白相互作用。

  公开号：

  WO2011140333A1

文献信息

• Compounds and Compositions That Bind and Stabilize Transthyretin and Their Use for Inhibiting Transthyretin Amyloidosis and Protein-Protein Interactions
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20140179751A1

  公开（公告）日：2014-06-26

  Disclosed herein are compounds and compositions thereof which find use in increasing stability of proteins particularly proteins that tend to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of proteins and thereby decreasing aggregate formation by these proteins. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

  本文揭示了一些化合物及其组合物，这些化合物可用于增加蛋白质的稳定性，特别是那些易于错误折叠并形成聚集物的蛋白质。本文还提供了使用这些化合物和组合物来增加蛋白质稳定性并从而减少这些蛋白质形成聚集物的方法。本文还揭示了一些异双功能化合物，其中包括通过连接剂将TTR结合化合物连接到靶向基团的，用于破坏目标蛋白质的蛋白质-蛋白质相互作用。
• [EN] TRANSTHYRETIN STABILIZERS AND THEIR USE FOR INHIBITING TRANSTHYRETIN AMYLOIDOSIS AND PROTEIN-PROTEIN INTERACTIONS<br/>[FR] STABILISANTS DE TRANSTHYRÉTINE ET LEUR UTILISATION POUR INHIBER L'AMYLOSE DE LA TRANSTHYRÉTINE ET LES INTERACTIONS PROTÉINE-PROTÉINE
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2014100227A1

  公开（公告）日：2014-06-26

  Disclosed herein are compounds and compositions thereof which find use in increasing stability of proteins particularly proteins that tend to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of proteins and thereby decreasing aggregate formation by these proteins. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

  本文公开了一些化合物及其组合物，可用于增加蛋白质的稳定性，特别是那些容易错折和形成聚集体的蛋白质。本文还提供了使用这些化合物和组合物来增加蛋白质稳定性并因此减少这些蛋白质聚集体形成的方法。本文还公开了异二功能化合物，其中包括通过连接剂连接到靶向基团的TTR结合化合物，用于破坏目标蛋白质的PPI。
• Identification of stabilizers of multimeric proteins
  申请人：Graef Isabella A.

  公开号：US08877795B2

  公开（公告）日：2014-11-04

  Disclosed herein are compounds and compositions thereof which find use in increasing stability of TTR tetramers reducing its tendency to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of TTR and thereby decreasing aggregate formation by TTR. Also disclosed herein are methods to screen for candidate compounds that increase stability of TTR. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

  本文公开了一些化合物及其组合物，可用于增加TTR四聚体的稳定性，减少其错折和聚集的倾向。本文还提供了使用这些化合物和组合物以增加TTR稳定性并从而减少TTR聚集形成的方法。本文还公开了用于筛选增加TTR稳定性的候选化合物的方法。本文还公开了异双功能化合物，其中包括通过连接剂连接到靶向基团上的TTR结合化合物，用于破坏目标蛋白的PPIs。
• Identification of Stabilizers of Multimeric Proteins
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20150126532A1

  公开（公告）日：2015-05-07

  Disclosed herein are compounds and compositions thereof which find use in increasing stability of TTR tetramers reducing its tendency to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of TTR and thereby decreasing aggregate formation by TTR. Also disclosed herein are methods to screen for candidate compounds that increase stability of TTR. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

  本文公开了一些化合物及其组合物，可用于增加TTR四聚体的稳定性，减少其错折和聚集的倾向。本文还提供了使用这些化合物和组合物增加TTR稳定性、从而减少TTR聚集形成的方法。本文还公开了筛选候选化合物以增加TTR稳定性的方法。本文还公开了异双功能化合物，其中包括一个TTR结合化合物通过连接子连接到一个靶向基团上，用于破坏目标蛋白质的蛋白质相互作用。
• Compounds and compositions that bind and stabilize transthyretin and their use for inhibiting transthyretin amyloidosis and protein-protein interactions
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10398681B2

  公开（公告）日：2019-09-03

  Disclosed herein are compounds and compositions thereof which find use in increasing stability of proteins particularly proteins that tend to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of proteins and thereby decreasing aggregate formation by these proteins. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

  本文公开的化合物及其组合物可用于提高蛋白质的稳定性，特别是容易折叠错误和形成聚集体的蛋白质。本文还提供了使用这些化合物和组合物提高蛋白质稳定性从而减少这些蛋白质形成聚集体的方法。本文还公开了异官能化合物，其中包括通过连接体与靶向分子连接的 TTR 结合化合物，用于破坏靶蛋白的 PPI。