4-(azepan-1-ylcarbonyl)-2-(4-ethoxyphenyl)-6,7-dimethoxyisoquinolin-1(2H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-(azepan-1-ylcarbonyl)-2-(4-ethoxyphenyl)-6,7-dimethoxyisoquinolin-1(2H)-one
• 英文别名: 4-(Azepane-1-carbonyl)-2-(4-ethoxyphenyl)-6,7-dimethoxyisoquinolin-1-one
• 化学式: C₂₆H₃₀N₂O₅
• 分子量: 450.535
• InChiKey: HAIWXHVWIBAESO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6,7-甲氧基-异色满-1,3-二酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 4-(azepan-1-ylcarbonyl)-2-(4-ethoxyphenyl)-6,7-dimethoxyisoquinolin-1(2H)-one
  参考文献：
  名称：

  Identification of potent lysophosphatidic acid receptor 5 (LPA5) antagonists as potential analgesic agents

  摘要：

  Lysophosphatidic acid (LPA) plays an important role in a variety of cellular functions. In particular, LPA5 receptor is highly expressed in spinal cord and dorsal root ganglion, which are associated with pain. This fact prompted us to hypothesize that LPA5 antagonists show analgesic effects. To search for potent LPA5 antagonists with blood brain barrier (BBB) permeability, we conducted high throughput screening (HTS). In HTS campaign, we found a 2H-isoquinoline-1-one scaffold showing antagonistic activity against LPA5 and synthesized a series of 2H-isoquinoline-1-one derivatives and evaluated their LPA5 activities. Among these compounds, compound 7e showed potent LPA5 activity with an IC50 value of 0.12 mu M, and acceptable BBB permeability. Furthermore, it showed effective analgesic effect in a chronic constriction injury rat model. Therefore, 7e may have a potential as novel pain therapeutic approach. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.038