7-methoxy-2-(4'-trifluoromethylbenzyl)-4H-1-benzopyran-4-one-3-carboxylic acid | 433682-94-1

• 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: 7-methoxy-2-(4'-trifluoromethylbenzyl)-4H-1-benzopyran-4-one-3-carboxylic acid
• CAS: 433682-94-1
• 化学式: C₁₉H₁₃F₃O₅
• 分子量: 378.304
• InChiKey: GURCPKIWMJZJRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.11
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  76.74
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  7-methoxy-2-(4'-trifluoromethylbenzyl)-4H-1-benzopyran-4-one-3-carboxylic acid 以 喹啉 为溶剂， 反应 0.17h， 以80%的产率得到7-methoxy-2-(4'-trifluoromethylbenzyl)-4H-1-benzopyran-4-one
  参考文献：
  名称：

  Binding of 1-Benzopyran-4-one Derivatives to Aldose Reductase: A Free Energy Perturbation Study

  摘要：

  The relative binding affinities to human aldose reductase (ALR2) of three new 7-hydroxy-2-benzyl-4H-1-benzopyran-4-one inhibitors were predicted by free energy perturbation (FEP) simulations. Molecular substitutions were specifically designed to investigate the role of hydrogen bonding at the active site of ALR2. Starting from the lead inhibitor 7-hydroxy-2-(4'-hydroxy-benzyl)-4H-1-benzopyran-4-one, the 4'-hydroxyl was mutated to methyl and to trifluoromethyl, and an hydroxyl at position 8 was additionally introduced. Once synthesized and tested as inhibitors of ALR2, the compounds displayed variations of K-i that were in qualitative to quantitative agreement with the calculated relative free energies of binding. The results, discussed in terms of balance between free energies of solvation and free energies of binding to ALR2, elucidate the importance of hydrogen bonding with Thr113 and with Trp111 and cofactor, and provide a rationale to the observed differences in binding affinities. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00408-4
• 作为产物：
  描述：

  3-(2-羟基-4-甲氧基苯基)-3-氧丙酸甲酯 在 magnesium hydroxide 、 氢溴酸 作用下， 以 乙醇 为溶剂， 反应 17.0h， 生成 7-methoxy-2-(4'-trifluoromethylbenzyl)-4H-1-benzopyran-4-one-3-carboxylic acid
  参考文献：
  名称：

  Binding of 1-Benzopyran-4-one Derivatives to Aldose Reductase: A Free Energy Perturbation Study

  摘要：

  The relative binding affinities to human aldose reductase (ALR2) of three new 7-hydroxy-2-benzyl-4H-1-benzopyran-4-one inhibitors were predicted by free energy perturbation (FEP) simulations. Molecular substitutions were specifically designed to investigate the role of hydrogen bonding at the active site of ALR2. Starting from the lead inhibitor 7-hydroxy-2-(4'-hydroxy-benzyl)-4H-1-benzopyran-4-one, the 4'-hydroxyl was mutated to methyl and to trifluoromethyl, and an hydroxyl at position 8 was additionally introduced. Once synthesized and tested as inhibitors of ALR2, the compounds displayed variations of K-i that were in qualitative to quantitative agreement with the calculated relative free energies of binding. The results, discussed in terms of balance between free energies of solvation and free energies of binding to ALR2, elucidate the importance of hydrogen bonding with Thr113 and with Trp111 and cofactor, and provide a rationale to the observed differences in binding affinities. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00408-4