6-[2-(ethylamino)propanoyl]-2H-1,4-benzoxazin-3(4H)-one | 1454580-30-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-[2-(ethylamino)propanoyl]-2H-1,4-benzoxazin-3(4H)-one
• 英文别名: 6-[2-(ethylamino)propanoyl]-4H-1,4-benzoxazin-3-one
• CAS: 1454580-30-3
• 化学式: C₁₃H₁₆N₂O₃
• 分子量: 248.282
• InChiKey: VKQSOZYGULLSPJ-UHFFFAOYSA-N

物化性质

• 沸点：
  472.1±45.0 °C(predicted)
• 密度：
  1.181±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  67.43
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6-[2-(ethylamino)propanoyl]-2H-1,4-benzoxazin-3(4H)-one 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 生成 6-[1-ethyl-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：

  2H-1,4-苯并噁嗪-3(4H)-酮 在 aluminum (III) chloride 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 24.0h， 生成 6-[2-(ethylamino)propanoyl]-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

文献信息

• Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists
  作者：Tomoaki Hasui、Taiichi Ohra、Norio Ohyabu、Kouhei Asano、Hideki Matsui、Atsushi Mizukami、Noriyuki Habuka、Satoshi Sogabe、Satoshi Endo、Christopher S. Siedem、Tony P. Tang、Cassandra Gauthier、Lisa A. De Meese、Steven A. Boyd、Shoji Fukumoto

  DOI：10.1016/j.bmc.2013.07.043

  日期：2013.10

  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.