4-(5-Fluoro-2-methoxy-phenyl)-4-methyl-2-oxo-pentanoic acid (1-oxo-1,3-dihydro-isobenzofuran-5-yl)-amide | 934391-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 4-(5-Fluoro-2-methoxy-phenyl)-4-methyl-2-oxo-pentanoic acid (1-oxo-1,3-dihydro-isobenzofuran-5-yl)-amide
• CAS: 934391-82-9
• 化学式: C₂₁H₂₀FNO₅
• 分子量: 385.392
• InChiKey: AGYKNHICYLGXCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-(5-Fluoro-2-methoxy-phenyl)-4-methyl-2-oxo-pentanoic acid (1-oxo-1,3-dihydro-isobenzofuran-5-yl)-amide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-(2-methylbenzyl)pentanoic acid (1-oxo-1,3-dihydroisobenzofuran-5-yl)amide
  参考文献：
  名称：

  Trifluoromethyl group as a pharmacophore: Effect of replacing a CF3 group on binding and agonist activity of a glucocorticoid receptor ligand

  摘要：

  Compound 1, a potent glucocorticoid receptor ligand, contains a quaternary carbon bearing trifluoromethyl and hydroxyl groups. This paper describes the effect of replacing the trifluoromethyl group on binding and agonist activity of the GR ligand 1. The results illustrate that replacing the CF3 group with a cyclohexylmethyl or benzyl group maintains the GR binding potency. These substitutions alter the functional behavior of the GR ligands from agonists to antagonists. Docking studies suggest that the benzyl analog 19 binds in a similar fashion as the GR antagonist, RU486. The central benzyl group of 19 and the C-11 dimethylaniline moiety of RU486 overlay. Binding of compound 19 is believed to force helix 12 to adopt an open conformation and this leads to the antagonist properties of the non-CF3 ligands carrying a large group at the center of the molecule. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.025
• 作为产物：
  描述：

  4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentanoic acid 在 氯化亚砜 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 4-(5-Fluoro-2-methoxy-phenyl)-4-methyl-2-oxo-pentanoic acid (1-oxo-1,3-dihydro-isobenzofuran-5-yl)-amide
  参考文献：
  名称：

  Trifluoromethyl group as a pharmacophore: Effect of replacing a CF3 group on binding and agonist activity of a glucocorticoid receptor ligand

  摘要：

  Compound 1, a potent glucocorticoid receptor ligand, contains a quaternary carbon bearing trifluoromethyl and hydroxyl groups. This paper describes the effect of replacing the trifluoromethyl group on binding and agonist activity of the GR ligand 1. The results illustrate that replacing the CF3 group with a cyclohexylmethyl or benzyl group maintains the GR binding potency. These substitutions alter the functional behavior of the GR ligands from agonists to antagonists. Docking studies suggest that the benzyl analog 19 binds in a similar fashion as the GR antagonist, RU486. The central benzyl group of 19 and the C-11 dimethylaniline moiety of RU486 overlay. Binding of compound 19 is believed to force helix 12 to adopt an open conformation and this leads to the antagonist properties of the non-CF3 ligands carrying a large group at the center of the molecule. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.025