2-amino-7-hydroxy-4-[4-(2-morpholin-4-ylethoxy)phenyl]-4H-chromene-3-carbonitrile

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: 2-amino-7-hydroxy-4-[4-(2-morpholin-4-ylethoxy)phenyl]-4H-chromene-3-carbonitrile
• 化学式: C₂₂H₂₃N₃O₄
• 分子量: 393.442
• InChiKey: CKBYHRUUVKOLSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  100.97
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  4-(2-氯乙基)吗啉 在 哌啶 、 四丁基溴化铵 、 potassium carbonate 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 4.17h， 生成 2-amino-7-hydroxy-4-[4-(2-morpholin-4-ylethoxy)phenyl]-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening

  摘要：

  4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor alpha and beta with low nanomolar affinity and <20-fold selectivity for alpha over beta and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERa (compound 35; 350-fold selectivity) or ER beta (compound 42; 170-fold selectivity).

  DOI：

  10.1016/j.bmc.2019.115261

文献信息

• Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening
  作者：Miriam Carr、Andrew J.S. Knox、Daniel K. Nevin、Niamh O'Boyle、Shu Wang、Billy Egan、Thomas McCabe、Brendan Twamley、Daniela M. Zisterer、David G. Lloyd、Mary J. Meegan

  DOI：10.1016/j.bmc.2019.115261

  日期：2020.3

  4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor alpha and beta with low nanomolar affinity and <20-fold selectivity for alpha over beta and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERa (compound 35; 350-fold selectivity) or ER beta (compound 42; 170-fold selectivity).