5-(1,2-dithiolan-3-yl)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]pentanamide | 1002100-46-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-(1,2-dithiolan-3-yl)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]pentanamide
• 英文别名: 5-(dithiolan-3-yl)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]pentanamide
• CAS: 1002100-46-0
• 化学式: C₁₈H₂₄N₂O₂S₂
• 分子量: 364.533
• InChiKey: ANAYYVXDULHHDL-UHFFFAOYSA-N

物化性质

• 沸点：
  669.0±45.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-羟基色胺盐酸盐 、 Thioctic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.25h， 以86%的产率得到5-(1,2-dithiolan-3-yl)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]pentanamide
  参考文献：
  名称：

  New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

  摘要：

  N-Arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of alpha- and gamma-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbarnate 3f (OMDM 106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50 = 0.5 mu M). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formal in-induced hyperalgesia in mice.

  DOI：

  10.1021/jm070678q

文献信息

• New <i>N</i>-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain
  作者：Giorgio Ortar、Maria Grazia Cascio、Luciano De Petrocellis、Enrico Morera、Francesca Rossi、Aniello Schiano-Moriello、Marianna Nalli、Vito de Novellis、David F. Woodward、Sabatino Maione、Vincenzo Di Marzo

  DOI：10.1021/jm070678q

  日期：2007.12.27

  N-Arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of alpha- and gamma-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbarnate 3f (OMDM 106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50 = 0.5 mu M). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formal in-induced hyperalgesia in mice.