5-bromo-2′,4′-difluoro-4-hydroxy-[1,1′-biphenyl]-3-carboxylic acid

• 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: 5-bromo-2′,4′-difluoro-4-hydroxy-[1,1′-biphenyl]-3-carboxylic acid
• 英文别名: 3-Bromo-5-(2,4-difluorophenyl)-2-hydroxybenzoic acid
• 化学式: C₁₃H₇BrF₂O₃
• 分子量: 329.098
• InChiKey: HKHBYVPMCRRTKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  二氟尼柳 在 pyridine hydrobromideperbromide polymer-bound 作用下， 以 二氯甲烷 为溶剂， 以52%的产率得到5-bromo-2′,4′-difluoro-4-hydroxy-[1,1′-biphenyl]-3-carboxylic acid
  参考文献：
  名称：

  Modulation of the Fibrillogenesis Inhibition Properties of Two Transthyretin Ligands by Halogenation

  摘要：

  The amyloidogenic protein transthyretin (TTR) is thought to aggregate into amyloid fibrils by tetramer dissociation which can be inhibited by a number of small molecule compounds. Our analysis of a series of crystallographic protein-inhibitor complexes has shown no clear correlation between the observed molecular interactions and the in vitro activity of the inhibitors. From this analysis, it emerged that halogen bonding (XB) could be mediating some well-known TTR inhibitors has shown that while flufenamic key interactions. Analysis of the halogenated derivatives of two acid affinity for TTR was unchanged by halogenation, diflunisal gradually improves binding up to 1 order of magnitude after iodination through interactions that can be interpreted as a suboptimal XB (carbonyl Thr106: I...O distance 3.96-4.05 angstrom; C-I angle 152-156 degrees) or as rather optimized van der Waals contacts or as a mixture of both. These results illustrate the potential of halogenation strategies in designing and optimizing TTR fibrillogenesis inhibitors.

  DOI：

  10.1021/jm401061w

文献信息

• Modulation of the Fibrillogenesis Inhibition Properties of Two Transthyretin Ligands by Halogenation
  作者：Ellen Y. Cotrina、Marta Pinto、Lluís Bosch、Marta Vilà、Daniel Blasi、Jordi Quintana、Nuria B. Centeno、Gemma Arsequell、Antoni Planas、Gregorio Valencia

  DOI：10.1021/jm401061w

  日期：2013.11.27

  The amyloidogenic protein transthyretin (TTR) is thought to aggregate into amyloid fibrils by tetramer dissociation which can be inhibited by a number of small molecule compounds. Our analysis of a series of crystallographic protein-inhibitor complexes has shown no clear correlation between the observed molecular interactions and the in vitro activity of the inhibitors. From this analysis, it emerged that halogen bonding (XB) could be mediating some well-known TTR inhibitors has shown that while flufenamic key interactions. Analysis of the halogenated derivatives of two acid affinity for TTR was unchanged by halogenation, diflunisal gradually improves binding up to 1 order of magnitude after iodination through interactions that can be interpreted as a suboptimal XB (carbonyl Thr106: I...O distance 3.96-4.05 angstrom; C-I angle 152-156 degrees) or as rather optimized van der Waals contacts or as a mixture of both. These results illustrate the potential of halogenation strategies in designing and optimizing TTR fibrillogenesis inhibitors.