6-Bromo-2-(3,5-dihydroxy-phenyl)-4-oxo-4H-chromene-8-carboxylic acid ethyl ester | 207617-55-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 6-Bromo-2-(3,5-dihydroxy-phenyl)-4-oxo-4H-chromene-8-carboxylic acid ethyl ester
• 英文别名: Ethyl 6-bromo-2-(3,5-dihydroxyphenyl)-4-oxochromene-8-carboxylate
• CAS: 207617-55-8
• 化学式: C₁₈H₁₃BrO₆
• 分子量: 405.202
• InChiKey: INFBIQHHPHTHPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-Bromo-2-(3,5-dihydroxy-phenyl)-4-oxo-4H-chromene-8-carboxylic acid ethyl ester 在 sodium hydroxide 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-[3,5-Bis-(quinolin-2-ylmethoxy)-phenyl]-6-bromo-4-oxo-4H-chromene-8-carboxylic acid
  参考文献：
  名称：

  Synthesis of 3-and 5′-substituted flavone-8-carboxylic acids as ‘three-armed’ leukotriene CysLT1 receptor antagonists

  摘要：

  Molecular modelling of leukotriene CysLT(1) receptor antagonists have suggested that in addition to the two binding sites for a lipophilic and an acidic group, the receptor has a 'third pocket' to accommodate 'three-armed' ligands such as montelukast 1. Based on the most rigid CysLT(1) receptor antagonist 3'-[2-(2-quinolinyl)ethenyl]flavone-8-carboxylic acid 2, we have synthesised 3- and 5'-substituted flavone derivatives to probe this additional binding pocket. Introduction of large substituents, e.g. 2-quinolinyl-methoxy, to the C5' position of the flavone skeleton abolished the CysLT(1) receptor affinity whereas the same modification at the C3 position yielded a potent CysLT antagonist. This observation implies that the third binding pocket of the receptor has considerable steric tolerance, probably corresponding to the substituents at C3 of the flavone skeleton. Further modification by introducing a C3 substituent containing a basic nitrogen resulted in compound 6g with potent H-1 antihistaminic activity although the CysLT(1) antagonistic activity was much reduced. Further study on the CysLT(1) receptor recognition of three armed antagonists may facilitate the design of more effective antiasthmatic agents, e.g. dual antagonists of histamine H-1 and leukotriene CysLT(1) receptors. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80034-2
• 作为产物：
  描述：

  1-(5-bromo-3-ethoxycarbonyl-2-hydroxyphenyl)-3-(3,5-dimethoxyphenyl)propane-1,3-dione 在 盐酸 、 硫酸 、 三溴化硼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 84.0h， 生成 6-Bromo-2-(3,5-dihydroxy-phenyl)-4-oxo-4H-chromene-8-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis of 3-and 5′-substituted flavone-8-carboxylic acids as ‘three-armed’ leukotriene CysLT1 receptor antagonists

  摘要：

  Molecular modelling of leukotriene CysLT(1) receptor antagonists have suggested that in addition to the two binding sites for a lipophilic and an acidic group, the receptor has a 'third pocket' to accommodate 'three-armed' ligands such as montelukast 1. Based on the most rigid CysLT(1) receptor antagonist 3'-[2-(2-quinolinyl)ethenyl]flavone-8-carboxylic acid 2, we have synthesised 3- and 5'-substituted flavone derivatives to probe this additional binding pocket. Introduction of large substituents, e.g. 2-quinolinyl-methoxy, to the C5' position of the flavone skeleton abolished the CysLT(1) receptor affinity whereas the same modification at the C3 position yielded a potent CysLT antagonist. This observation implies that the third binding pocket of the receptor has considerable steric tolerance, probably corresponding to the substituents at C3 of the flavone skeleton. Further modification by introducing a C3 substituent containing a basic nitrogen resulted in compound 6g with potent H-1 antihistaminic activity although the CysLT(1) antagonistic activity was much reduced. Further study on the CysLT(1) receptor recognition of three armed antagonists may facilitate the design of more effective antiasthmatic agents, e.g. dual antagonists of histamine H-1 and leukotriene CysLT(1) receptors. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80034-2

文献信息

• Synthesis of 3-and 5′-substituted flavone-8-carboxylic acids as ‘three-armed’ leukotriene CysLT1 receptor antagonists
  作者：Mariël E. Zwaagstra、Ronald E.M. Korthouwer、Henk Timmerman、Ming-Qiang Zhang

  DOI：10.1016/s0223-5234(98)80034-2

  日期：1998.2

  Molecular modelling of leukotriene CysLT(1) receptor antagonists have suggested that in addition to the two binding sites for a lipophilic and an acidic group, the receptor has a 'third pocket' to accommodate 'three-armed' ligands such as montelukast 1. Based on the most rigid CysLT(1) receptor antagonist 3'-[2-(2-quinolinyl)ethenyl]flavone-8-carboxylic acid 2, we have synthesised 3- and 5'-substituted flavone derivatives to probe this additional binding pocket. Introduction of large substituents, e.g. 2-quinolinyl-methoxy, to the C5' position of the flavone skeleton abolished the CysLT(1) receptor affinity whereas the same modification at the C3 position yielded a potent CysLT antagonist. This observation implies that the third binding pocket of the receptor has considerable steric tolerance, probably corresponding to the substituents at C3 of the flavone skeleton. Further modification by introducing a C3 substituent containing a basic nitrogen resulted in compound 6g with potent H-1 antihistaminic activity although the CysLT(1) antagonistic activity was much reduced. Further study on the CysLT(1) receptor recognition of three armed antagonists may facilitate the design of more effective antiasthmatic agents, e.g. dual antagonists of histamine H-1 and leukotriene CysLT(1) receptors. (C) Elsevier, Paris.