ethyl 2-amino-7-hydroxy-4-(2-nitrophenyl)-4H-chromene-3-carboxylate | 1325714-87-1

• 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: ethyl 2-amino-7-hydroxy-4-(2-nitrophenyl)-4H-chromene-3-carboxylate
• CAS: 1325714-87-1
• 化学式: C₁₈H₁₆N₂O₆
• 分子量: 356.335
• InChiKey: KAOXCRMXOXAWJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氰乙酸乙酯 、 邻硝基苯甲醛 、 间苯二酚 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以32%的产率得到ethyl 2-amino-7-hydroxy-4-(2-nitrophenyl)-4H-chromene-3-carboxylate
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationships and Brain Uptake of a Novel Series of Benzopyran Inhibitors of Insulin-Regulated Aminopeptidase

  摘要：

  Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) enhance fear avoidance and spatial memory and accelerate spatial learning in a number of memory paradigms. Using a virtual screening approach, a series of benzopyran compounds was identified that inhibited the catalytic activity of IRAP, ultimately resulting in the identification of potent and specific inhibitors. The present study describes the medicinal chemistry campaign that led to the development of the lead candidate, 3, highlighting the key structural features considered as critical for binding. Furthermore, the in vivo pharmacokinetics and brain uptake of compounds (1 and 3) were assessed in rats and were complemented with in vitro human and rat microsomal stability studies. Following intravenous administration to rodents, 3 exhibits brain exposure, albeit it is rapidly converted to 1, a compound which also exhibits potent inhibition of IRAP.

  DOI：

  10.1021/jm401540f

文献信息

• Synthesis, Structure–Activity Relationships and Brain Uptake of a Novel Series of Benzopyran Inhibitors of Insulin-Regulated Aminopeptidase
  作者：Simon J. Mountford、Anthony L. Albiston、William N. Charman、Leelee Ng、Jessica K. Holien、Michael W. Parker、Joseph A. Nicolazzo、Philip E. Thompson、Siew Yeen Chai

  DOI：10.1021/jm401540f

  日期：2014.2.27

  Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) enhance fear avoidance and spatial memory and accelerate spatial learning in a number of memory paradigms. Using a virtual screening approach, a series of benzopyran compounds was identified that inhibited the catalytic activity of IRAP, ultimately resulting in the identification of potent and specific inhibitors. The present study describes the medicinal chemistry campaign that led to the development of the lead candidate, 3, highlighting the key structural features considered as critical for binding. Furthermore, the in vivo pharmacokinetics and brain uptake of compounds (1 and 3) were assessed in rats and were complemented with in vitro human and rat microsomal stability studies. Following intravenous administration to rodents, 3 exhibits brain exposure, albeit it is rapidly converted to 1, a compound which also exhibits potent inhibition of IRAP.