2-hydroxy-10(Z)-nonadecenoic acid | 81861-41-8

• 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-hydroxy-10(Z)-nonadecenoic acid
• 英文别名: (Z)-2-hydroxynonadec-10-enoic acid
• CAS: 81861-41-8
• 化学式: C₁₉H₃₆O₃
• 分子量: 312.493
• InChiKey: ATWDCEPWLPSLIX-KTKRTIGZSA-N

物化性质

• 沸点：
  426.0±25.0 °C(Predicted)
• 密度：
  0.951±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  22
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxy-10(Z)-nonadecenoic acid 在 sodium hydroxide 、 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 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Differential Inhibition of Group IVA and Group VIA Phospholipases A₂ by 2-Oxoamides

  摘要：

  Inhibitors of the Group IVA phospholipase A(2) (GIVA cPLA(2)) and GVIA iPLA(2) are useful tools for defining the roles of these enzymes in cellular signaling and inflammation. We have developed inhibitors of GVIA iPLA(2) building upon the 2-oxoamide backbone that are uncharged, containing ester groups. Although the most potent inhibitors of GVIA iPLA(2) also inhibited GIVA cPLA(2), there were three 2-oxoamide compounds that selectively and weakly inhibited GVIA iPLA(2). We further show that several potent 2-oxoamide inhibitors of GIVA cPLA(2) containing free carboxylic groups (Kokotos et al. J. Med. Chem. 2002, 45, 2891-2893) do not inhibit GVIA iPLA(2) and are, therefore, selective GIVA cPLA(2) inhibitors.

  DOI：

  10.1021/jm050993h
• 作为产物：
  描述：

  (Z)-十八碳-9-烯醛 在 盐酸 、 氢氧化钾 、 sodium hydrogensulfite 作用下， 以 乙醇 、 水 为溶剂， 反应 58.0h， 生成 2-hydroxy-10(Z)-nonadecenoic acid
  参考文献：
  名称：

  Darmstoff analogs. 2. Ring and side chain effects on smooth muscle contraction

  摘要：

  2-cis-delta 8-Heptadecenyl-4-(hydroxymethyl)-1,3-dioxolane monosodium phosphate (1b) has been shown to be present as a major component of Darmstoff in mammalian intestine and to be a potent inducer for contraction of intestinal smooth muscle. The analogous 2-pentadecyl material 1a, also found abundantly in the intestine, is inactive. In this study, synthesis of phosphorylated hydroxymethyl-1,4-dioxanes, -tetrahydrofurans, -cyclopentanes, and -oxathiolanes bearing both oleyl and palmityl side chains is reported. Of these, 2-(hydroxymethyl)-5-cis-delta 8-heptadecenyl-1,4-dioxane monosodium phosphate (2b) exhibits about 12% of the activity of 1b. Its pentadecyl analogue 2a, like 1a, is totally inactive, as are all other compounds prepared. The results indicate that Darmstoff-like compounds exhibit specific chemical requirements for activity and that where activity is encountered, the side-chain specificity noted in 1a and 1b can be preserved.

  DOI：

  10.1021/jm00344a006

文献信息

• [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。
• Inhibition of Oleamide Hydrolase Catalyzed Hydrolysis of the Endogenous Sleep-Inducing Lipid <i>cis</i>-9-Octadecenamide
  作者：Jean E. Patterson、Ian R. Ollmann、Benjamin F. Cravatt、Dale L. Boger、Chi -Huey Wong、Richard A. Lerner

  DOI：10.1021/ja954064z

  日期：1996.1.1

  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.
• 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