N-oleoylserotonin | 1002100-44-8

• 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: N-oleoylserotonin
• 英文别名: (9Z)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]octadec-9-enamide；(Z)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]octadec-9-enamide
• CAS: 1002100-44-8
• 化学式: C₂₈H₄₄N₂O₂
• 分子量: 440.67
• InChiKey: LCQKHZYXPCLVBI-KTKRTIGZSA-N

物化性质

• 溶解度：
  DMSO 中≤15mg/ml；二甲基甲酰胺中≤15mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  32
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境中使用。

制备方法与用途

油酸基5-羟色胺是一种TRPV1拮抗剂，其对人TRPV1的半抑制浓度（IC50）值为2.57微摩尔。

反应信息

• 作为产物：
  描述：

  油酸 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 N-oleoylserotonin
  参考文献：
  名称：

  Synthesis and Evaluation of Fatty Acid Amides on the <i>N</i>-Oleoylethanolamide-Like Activation of Peroxisome Proliferator Activated Receptor α

  摘要：

  合成了一系列脂肪酸酰胺，并评估了它们在正常大鼠肝细胞系clone 9中对过氧化物酶体增殖物激活剂受体α（PPAR-α）的激动活性。通过实时反转录聚合酶链反应（RT-PCR）测定了PPAR-α下游基因肉碱棕榈酰转移酶-1和线粒体3-羟基-3-甲基戊二酰辅酶A合酶的mRNA，作为PPAR-α激动活性的指标。我们合成了九种油酸酰胺。它们的PPAR-α激动活性按递减顺序为N-油酸组胺（OLHA）、N-油酸甘氨酸、油酰胺、N-油酸酪胺、N-油酸血清素和Olvanil。最高活性出现在OLHA。我们还合成并评估了九种N-酰基组胺（N-acyl-HAs）。其中，OLHA、C16:0-HA和C18:1Δ9-trans-HA显示出相似的活性。由于饱和脂肪酸不同链长的活性在C16:0-HA处达到峰值。PPAR-α拮抗剂GW6471抑制了OLHA和N-油酸乙醇酰胺（OEA对PPAR-α下游基因的诱导。这些数据表明N-酰基组胺可以被视为新的PPAR-α激动剂。

  DOI：

  10.1248/cpb.c14-00881

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.
• Identification of an arylalkylamine<i>N</i>-acyltransferase from<i>Drosophila melanogaster</i>that catalyzes the formation of long-chain<i>N</i>-acylserotonins
  作者：Daniel R. Dempsey、Kristen A. Jeffries、Ryan L. Anderson、Anne-Marie Carpenter、Santiago Rodriquez Opsina、David J. Merkler

  DOI：10.1016/j.febslet.2013.12.027

  日期：2014.2.14

  Arylalkylamine N‐acyltransferase‐like 2 2 (AANATL2) from Drosophila melanogaster was expressed and shown to catalyze the formation of long‐chain N‐acylserotonins and N‐acydopamines. Subsequent identification of endogenous amounts of N‐acylserotonins and colocalization of these fatty acid amides and AANATL2 transcripts gives supporting evidence that AANATL2 has a role in the biosynthetic formation of these important cell signalling lipids.
• Synthesis and Evaluation of Fatty Acid Amides on the &lt;i&gt;N&lt;/i&gt;-Oleoylethanolamide-Like Activation of Peroxisome Proliferator Activated Receptor α
  作者：Koichi Takao、Kaori Noguchi、Yosuke Hashimoto、Akira Shirahata、Yoshiaki Sugita

  DOI：10.1248/cpb.c14-00881

  日期：——

  A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ9-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists.

  合成了一系列脂肪酸酰胺，并评估了它们在正常大鼠肝细胞系clone 9中对过氧化物酶体增殖物激活剂受体α（PPAR-α）的激动活性。通过实时反转录聚合酶链反应（RT-PCR）测定了PPAR-α下游基因肉碱棕榈酰转移酶-1和线粒体3-羟基-3-甲基戊二酰辅酶A合酶的mRNA，作为PPAR-α激动活性的指标。我们合成了九种油酸酰胺。它们的PPAR-α激动活性按递减顺序为N-油酸组胺（OLHA）、N-油酸甘氨酸、油酰胺、N-油酸酪胺、N-油酸血清素和Olvanil。最高活性出现在OLHA。我们还合成并评估了九种N-酰基组胺（N-acyl-HAs）。其中，OLHA、C16:0-HA和C18:1Δ9-trans-HA显示出相似的活性。由于饱和脂肪酸不同链长的活性在C16:0-HA处达到峰值。PPAR-α拮抗剂GW6471抑制了OLHA和N-油酸乙醇酰胺（OEA对PPAR-α下游基因的诱导。这些数据表明N-酰基组胺可以被视为新的PPAR-α激动剂。