2-Oxo-9Z-octadecenamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-Oxo-9Z-octadecenamide
• 英文别名: (Z)-2-oxooctadec-9-enamide
• 化学式: C₁₈H₃₃NO₂
• 分子量: 295.466
• InChiKey: IRAGOFPCHGZDIG-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  21
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-羟基油酸 在 ammonium hydroxide 、 重铬酸吡啶 、 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-Oxo-9Z-octadecenamide
  参考文献：
  名称：

  Inhibition of Oleamide Hydrolase Catalyzed Hydrolysis of the Endogenous Sleep-Inducing Lipid cis-9-Octadecenamide

  摘要：

  Oleamide (1, cis-9-octadecenamide) is a naturally occurring brain constituent that. has been shown to accumulate and disappear under conditions of sleep deprivation and sleep recovery, respectively. Synthetic 1 has been found to induce sleep in a structurally specific manner at nanomolar quantities. Hydrolysis of 1 by an enzyme (oleamide hydrolase) present in the cell membrane rapidly degrades oleamide to oleic acid (cis-9-octadecenoic acid). Such observations suggest 1 may constitute a prototypical member of a class of fatty acid primary amide biological signaling molecules in which the diversity and selectivity of function are derived from the length of the alkane chain as well as the position, stereochemistry, and degree of unsaturation. A series of inhibitors of oleamide hydrolase were designed and prepared which were expected to derive their properties through interactions with the putative active site cysteine residue within oleamide hydrolase. This approach yielded a series of rapid, selective, and highly potent inhibitors (K-i = 13 mu M to 1 nM) which in addition to their potential therapeutic value may serve as useful tools to define the biological role of oleamide.

  DOI：

  10.1021/ja954064z

文献信息

• Inhibitors of oleamide hydrolase
  申请人：The Scripps Research Institute

  公开号：US05856537A1

  公开（公告）日：1999-01-05

  Inhibitors of oleamide hydrolase, responsible for the hydrolysis of an endogenous sleep-inducing lipid (1, cis-9-octadecenamide) were designed and synthesized. The most potent inhibitors possess an electrophilic carbonyl group capable of reversibly forming a (thio) hemiacetal or (thio) hemiketal to mimic the transition state of a serine or cysteine protease catalyzed reaction. In particular, the tight binding .alpha.-keto ethyl ester 8 (1.4 nM) and the trifluoromethyl ketone inhibitor 12 (1.2 nM) were found to have exceptional inhibitory activity. In addition to the inhibitory activity, some of the inhibitors displayed agonist activity which resulted in the induction of sleep in laboratory animals.

  抑制剂的油酰胺水解酶，负责水解内源性诱导睡眠的脂质（1，顺式-9-十八碳烯酰胺）已被设计和合成。最有效的抑制剂具有一个亲电性羰基团，能够可逆地形成（硫）半缩醛或（硫）半缩酮，以模拟丝氨酸或半胱氨酸蛋白酶催化反应的过渡态。特别是，紧密结合的α-酮乙酯酯8（1.4 nM）和三氟甲基酮抑制剂12（1.2 nM）被发现具有异常的抑制活性。除了抑制活性外，一些抑制剂显示出激动剂活性，导致实验动物的睡眠诱导。
• [EN] INHIBITORS OF OLEAMIDE HYDROLASE<br/>[FR] INHIBITEURS DE L'OLEAMIDE HYDROLASE
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：WO1997049667A1

  公开（公告）日：1997-12-31

  (EN) Inhibitors of oleamide hydrolase, responsible for the hydrolysis of an endogenous sleep-inducing lipid (1, $i(cis)-9-octadecenamide) were designed and synthesized. The most potent inhibitors possess an electrophilic carbonyl group capable of reversibly forming a (thio) hemiacetal or (thio) hemiketal to mimic the transition state of a serine or cysteine protease catalyzed reaction. In particular, the tight binding $g(a)-keto ethyl ester 8 (1.4 nM) and the trifluoromethyl ketone inhibitor 12 (1.2 nM) were found to have exceptional inhibitory activity. In addition to the inhibitory activity, some of the inhibitors displayed agonist activity which resulted in the induction of sleep in laboratory animals.(FR) L'invention porte sur la conception et la synthèse d'inhibiteurs de l'oléamide hydrolase responsables de l'hydrolyse d'un lipide endogène provoquant le sommeil (1, $i(cis)-9-octadécènamide). Les inhibiteurs les plus puissants possèdent un groupe carbonyle électrophile capable de constituer de façon réversible un (thio) hémi-acétal ou (thio) hémi-cétal simulant l'état de transition d'une réaction catalysée par la sérine ou cystéine protéase. Il a été découvert en particulier que le $g(a)-céto-éthyl ester 8 (1,4 nM) à liaison renforcée et l'inhibiteur trifluorométhyl cétone 12 (1,2 nM) avaient une activité inhibitrice exceptionnelle. Outre leur activité inhibitrice, certains des inhibiteurs ont montré une activité agoniste ayant pour résultat d'induire le sommeil chez des animaux de laboratoire.

  (中) 设计并合成了一种抑制剂，其作用是抑制内源性诱导睡眠的脂质（1，$i(cis)-9-十八碳烯酰胺）的水解酶（oleamide hydrolase）。最有效的抑制剂具有亲电性羰基基团，能够可逆地形成（硫）半乙缩醛或（硫）半缩酮，以模拟丝氨酸或半胱氨酸蛋白酶催化反应的过渡态。特别是紧密结合的$g(a)-酮乙酯8（1.4 nM）和三氟甲基酮抑制剂12（1.2 nM）具有出色的抑制活性。除了抑制活性外，一些抑制剂还表现出激动剂活性，导致实验动物的睡眠诱导。
• INHIBITORS OF OLEAMIDE HYDROLASE
  申请人：The Scripps Research Institute

  公开号：EP0910561A1

  公开（公告）日：1999-04-28
• EP0910561A4
  申请人：——

  公开号：EP0910561A4

  公开（公告）日：2000-06-07
• US5856537A
  申请人：——

  公开号：US5856537A

  公开（公告）日：1999-01-05