N-(3,5-dibromo-4-hydroxyphenyl)-4-hydroxybenzamide | 1126079-26-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,5-dibromo-4-hydroxyphenyl)-4-hydroxybenzamide
• CAS: 1126079-26-2
• 化学式: C₁₃H₉Br₂NO₃
• 分子量: 387.027
• InChiKey: ITXBIHIPTIQREU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(3,5-dibromo-4-hydroxyphenyl)-4-methoxybenzamide 在 三溴化硼 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 18.0h， 以71%的产率得到N-(3,5-dibromo-4-hydroxyphenyl)-4-hydroxybenzamide
  参考文献：
  名称：

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

  摘要：

  Transthyretin (TTR) amyloidogenesis inhibitors are typically composed of two aromatic rings and a linker. We have previously established optimal structures for one aromatic ring and the linker. Herein, we employ a suboptimal linker and an optimal aryl-X substructure to rank order the desirability of aryl-Z substructures--using a library of 56 N-(3,5-dibromo-4-hydroxyphenyl)benzamides. Coconsideration of amyloid inhibition potency and ex vivo plasma TTR binding selectivity data reveal that 2,6, 2,5, 2, 3,4,5, and 3,5 substituted aryls bearing small substituents generate the most potent and selective inhibitors, in descending order. These benzamides generally lack undesirable thyroid hormone receptor binding and COX-1 inhibition activity. Three high-resolution TTR.inhibitor crystal structures (1.31-1.35 A) provide insight into why these inhibitors are potent and selective, enabling future structure-based design of TTR kinetic stabilizers.

  DOI：

  10.1021/jm801347s

文献信息

• 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。
• US8703815B2
  申请人：——

  公开号：US8703815B2

  公开（公告）日：2014-04-22
• US9771321B2
  申请人：——

  公开号：US9771321B2

  公开（公告）日：2017-09-26
• [EN] SMALL MOLECULES THAT COVALENTLY MODIFY TRANSTHYRETIN<br/>[FR] PETITES MOLÉCULES QUI MODIFIENT DE FAÇON COVALENTE LA TRANSTHYRÉTINE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2011075210A2

  公开（公告）日：2011-06-23

  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.