(E)-3-(4-fluoro-3,5-dimethylphenyl)-N-(2-(2-methyl-1H-indol-3-yl)ethyl)acrylamide | 1609030-71-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4-fluoro-3,5-dimethylphenyl)-N-(2-(2-methyl-1H-indol-3-yl)ethyl)acrylamide
• 英文别名: (E)-3-(4-fluoro-3,5-dimethylphenyl)-N-[2-(2-methyl-1H-indol-3-yl)ethyl]prop-2-enamide
• CAS: 1609030-71-8
• 化学式: C₂₂H₂₃FN₂O
• 分子量: 350.436
• InChiKey: GMXRAXYWXGWMIO-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1H-2-甲基-3-氨乙基吲哚 、 4-Fluoro-3,5-dimethylcinnamic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 (E)-3-(4-fluoro-3,5-dimethylphenyl)-N-(2-(2-methyl-1H-indol-3-yl)ethyl)acrylamide
  参考文献：
  名称：

  Lead Optimization Studies of Cinnamic Amide EP2 Antagonists

  摘要：

  Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (similar to 10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role.

  DOI：

  10.1021/jm5000672

文献信息

• Lead Optimization Studies of Cinnamic Amide EP2 Antagonists
  作者：Thota Ganesh、Jianxiong Jiang、Myung-Soon Yang、Ray Dingledine

  DOI：10.1021/jm5000672

  日期：2014.5.22

  Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (similar to 10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role.