(R)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine | 616884-63-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine
• 英文别名: OMDM-1；OMDM-2；(Z)-N-[(2R)-1-hydroxy-3-(4-hydroxyphenyl)propan-2-yl]octadec-9-enamide
• CAS: 616884-63-0
• 化学式: C₂₇H₄₅NO₃
• 分子量: 431.659
• InChiKey: ICDMLAQPOAVWNH-HAAQQRBASA-N

物化性质

• 熔点：
  88-89 °C
• 沸点：
  625.8±55.0 °C(Predicted)
• 密度：
  0.999±0.06 g/cm3(Predicted)
• 溶解度：
  在乙醇中溶解度为 10 mM，在 DMSO 中溶解度为 10 mM

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  31
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境

制备方法与用途

OMDM-2 是一种有效且选择性的、代谢稳定的anandamide细胞摄取(ACU)抑制剂，其Ki值为3.0 μM。

反应信息

• 作为产物：
  描述：

  油酸 、 BETA-氨基-4-羟基苯丙醇盐酸盐 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 、 TEA 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以83%的产率得到(R)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine
  参考文献：
  名称：

  The anandamide membrane transporter. Structure–activity relationships of anandamide and oleoylethanolamine analogs with phenyl rings in the polar head group region

  摘要：

  A new series of anandamide and N-oleoylethanolamine analogs, most of which with aromatic moieties in the head group region, has been synthesized and evaluated as inhibitors of anandamide uptake. Some of them efficaciously inhibit the uptake process with K-i values in the low micromolar range (2.4-21.2 muM). Strict structural requisites are needed to observe a significant inhibition and in no case inhibition of fatty acid amidohydrolase overlaps with inhibition of anandamide uptake. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.026

文献信息

• Novel selective and metabolically stable inhibitors of anandamide cellular uptake
  作者：Giorgio Ortar、Alessia Ligresti、Luciano De Petrocellis、Enrico Morera、Vincenzo Di Marzo

  DOI：10.1016/s0006-2952(03)00109-6

  日期：2003.5

  Novel aromatic analogues of N-oleoylethanolamine and N-arachidonoylethanolamine (anandamide, AEA) were synthesized and, based on the capability of similar compounds to interact with proteins of the endocannabinoid and endovanilloid signaling systems, were tested on: (i) cannabinoid CB1 and CB2 receptors; (ii) vanilloid VR1 receptors; (iii) anandamide cellular uptake (ACU); and (iv) the fatty acid amide hydrolase (FAAH). The (R)- and, particularly, the (S)-1'-(4-hydroxybenzyl) derivatives of N-oleoylethanolamine and AEA (OMDM-1, OMDM-2, OMDM-3, and OMDM-4) inhibited to a varied extent ACU in RBL-2H3 cells (K-i ranging between 2.4 and 17.7 muM), the oleoyl analogues (OMDM-1 and OMDM-2, K-i 2.4 and 3.0 muM, respectively) being 6- to 7-fold more potent than the arachidonoyl analogues (OMDM-3 and OMDM-4). These four compounds exhibited: (i) poor affinity for either CB1 (K(i)greater than or equal tomuM) or CB2 (K-i>10 muM) receptors in rat brain and spleen membranes, respectively; (ii) almost no activity at vanilloid receptors in the intracellular calcium assay carried out with intact cells over-expressing the human VR1 (EC(50)greater than or equal to10 muM); and (iii) no activity as inhibitors of FAAH in N18TG2 cell membranes (K-i>50 muM). The oleoyl- and arachidonoyl-N'-(4-hydroxy-3-methoxybenzyl)hydrazines (OMDM-5 and OMDM-6), inhibited ACU (K-i 4.8 and 7.0 muM, respectively), and were more potent as VR1 agonists (EC50 75 and 50 nM, respectively), weakly active as CB1 receptor ligands (K-i 4.9 and 3.2 muM, respectively), and inactive as CB2 ligands (K-i>5 muM) as well as on FAAH (K(i)greater than or equal to40 muM). In conclusion, we report two novel potent and selective inhibitors of ACU (OMDM-1 and OMDM-2) and one "hybrid" agonist of CB1 and VR1 receptors (OMDM-6). Unlike other compounds of the same type, OMDM-1, OMDM-2, and OMDM-6 were very stable to enzymatic hydrolysis by rat brain homogenates. (C) 2003 Elsevier Science Inc. All rights reserved.
• [EN] THERAPEUTIC RELEASE AGENTS<br/>[FR] AGENTS DE LIBÉRATION THÉRAPEUTIQUES
  申请人：ORGANON NV

  公开号：WO2008100977A2

  公开（公告）日：2008-08-21

  [EN] Pharmacological inhibition of fatty acid amide hydrolase (FAAH) activity leads to increased levels of fatty acid amides. Esters of alkylcarbamic acids are disclosed that are inhibitors of FAAH activity. Compounds disclosed herein inhibit FAAH activity. Described herein are processes for the preparation of esters of alkylcarbamic acid compounds, compositions that include them, and methods of use thereof.
  [FR] L'inhibition pharmacologique de l'activité de l'amide hydrolase d'acides gras (FAAH) entraîne une augmentation des taux d'amides d'acides gras. L'invention concerne des esters d'acides alkylcarbamiques qui constituent des inhibiteurs de l'activité de la FAAH. Les composés décrits inhibent l'activité de la FAAH. L'invention concerne aussi des procédés de préparation d'esters de composés d'acides alkylcarbamiques, des compositions renfermant ceux-ci et des procédés d'utilisation de celles-ci.
• The anandamide membrane transporter. Structure–activity relationships of anandamide and oleoylethanolamine analogs with phenyl rings in the polar head group region
  作者：Vincenzo Di Marzo、Alessia Ligresti、Enrico Morera、Marianna Nalli、Giorgio Ortar

  DOI：10.1016/j.bmc.2004.07.026

  日期：2004.10

  A new series of anandamide and N-oleoylethanolamine analogs, most of which with aromatic moieties in the head group region, has been synthesized and evaluated as inhibitors of anandamide uptake. Some of them efficaciously inhibit the uptake process with K-i values in the low micromolar range (2.4-21.2 muM). Strict structural requisites are needed to observe a significant inhibition and in no case inhibition of fatty acid amidohydrolase overlaps with inhibition of anandamide uptake. (C) 2004 Elsevier Ltd. All rights reserved.