3-({[(1R)-1-(4-fluorophenyl)ethyl](1H-pyrrolo[2,3-c]pyridin-5-ylcarbonyl)amino}methyl)benzoic acid | 1398583-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 3-({[(1R)-1-(4-fluorophenyl)ethyl](1H-pyrrolo[2,3-c]pyridin-5-ylcarbonyl)amino}methyl)benzoic acid
• 英文别名: 3-[[[(1R)-1-(4-fluorophenyl)ethyl]-(1H-pyrrolo[2,3-c]pyridine-5-carbonyl)amino]methyl]benzoic acid
• CAS: 1398583-03-3
• 化学式: C₂₄H₂₀FN₃O₃
• 分子量: 417.44
• InChiKey: ITUHWRUDZXIIHN-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  86.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 3-({[(1R)-1-(4-fluorophenyl)ethyl](1H-pyrrolo[2,3-c]pyridin-5-ylcarbonyl)amino}methyl)benzoic acid
  参考文献：
  名称：

  Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain

  摘要：

  The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 degrees C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.

  DOI：

  10.1021/ml500479v

文献信息

• Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain
  作者：Mark D. Andrews、Kerry af Forselles、Kevin Beaumont、Sébastien R. G. Galan、Paul A. Glossop、Mathilde Grenie、Alan Jessiman、Amy S. Kenyon、Graham Lunn、Graham Maw、Robert M. Owen、David C. Pryde、Dannielle Roberts、Thien Duc Tran

  DOI：10.1021/ml500479v

  日期：2015.4.9

  The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 degrees C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.