8-fluoro-6-[4-(4-fluorophenyl)-1-(4-methoxybenzyl)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2H-1,4-benzoxazin-3(4H)-one | 1454580-53-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 8-fluoro-6-[4-(4-fluorophenyl)-1-(4-methoxybenzyl)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2H-1,4-benzoxazin-3(4H)-one
• CAS: 1454580-53-0
• 化学式: C₂₇H₂₂F₂N₂O₄
• 分子量: 476.479
• InChiKey: HTQCEKQJPXKAPK-UHFFFAOYSA-N

物化性质

• 沸点：
  698.1±55.0 °C(predicted)
• 密度：
  1.342±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.65
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  67.87
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  8-fluoro-6-[4-(4-fluorophenyl)-1-(4-methoxybenzyl)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2H-1,4-benzoxazin-3(4H)-one 在 苯甲醚 、 三氟乙酸 作用下， 反应 12.0h， 以78%的产率得到8-fluoro-6-[4-(4-fluorophenyl)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists

  摘要：

  Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel, potent and selective mineralocorticoid receptor (MR) antagonists by the structure-based drug design approach utilizing the crystal structure of MR/compound complex. Introduction of lipophilic substituents directed toward the unfilled spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring, led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2-one 11i showed an excellent in vitro activity (MR binding IC50 = 43 nM) and high selectivity over closely related steroid receptors such as the androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for AR and PR, 100-fold for GR). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.043
• 作为产物：
  描述：

  ethyl N-[(4-fluorophenyl)acetyl]-N-(4-methoxybenzyl)alaninate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium hydride 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 8-fluoro-6-[4-(4-fluorophenyl)-1-(4-methoxybenzyl)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists

  摘要：

  Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel, potent and selective mineralocorticoid receptor (MR) antagonists by the structure-based drug design approach utilizing the crystal structure of MR/compound complex. Introduction of lipophilic substituents directed toward the unfilled spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring, led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2-one 11i showed an excellent in vitro activity (MR binding IC50 = 43 nM) and high selectivity over closely related steroid receptors such as the androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for AR and PR, 100-fold for GR). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.043