arachidonyl-(2'-fluoroethyl)amide

• 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: arachidonyl-(2'-fluoroethyl)amide
• 英文别名: O-585；(5Z,8Z,11Z,14Z)-N-(2-fluoroethyl)icosa-5,8,11,14-tetraenamide
• 化学式: C₂₂H₃₆FNO
• 分子量: 349.532
• InChiKey: DOGHEWWVBBVYEY-DOFZRALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  25
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  arachidonyl-(2'-fluoroethyl)amide 在 maltose-binding protein-recombinant fatty acid amide hydrolase 作用下， 以 aq. phosphate buffer 、 重水 为溶剂， 生成 2-氟乙胺
  参考文献：
  名称：

  基于片段的n-FABS NMR筛选应用于膜酶FAAH的开发

  摘要：

  片段的氟：我们证明了基于19 F NMR片段的生化筛选（n -FABS）在膜蛋白脂肪酸酰胺水解酶（FAAH）上的首次应用。通过这种方法鉴定出的片段命中具有对FAAH的微摩尔抑制值，显示了该方法在其他膜蛋白应用中的潜力。S：底物，P：产品。

  DOI：

  10.1002/cbic.201300347
• 作为产物：
  描述：

  花生四烯酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 arachidonyl-(2'-fluoroethyl)amide
  参考文献：
  名称：

  基于片段的n-FABS NMR筛选应用于膜酶FAAH的开发

  摘要：

  片段的氟：我们证明了基于19 F NMR片段的生化筛选（n -FABS）在膜蛋白脂肪酸酰胺水解酶（FAAH）上的首次应用。通过这种方法鉴定出的片段命中具有对FAAH的微摩尔抑制值，显示了该方法在其他膜蛋白应用中的潜力。S：底物，P：产品。

  DOI：

  10.1002/cbic.201300347

文献信息

• Novel Analogues of Arachidonylethanolamide (Anandamide):  Affinities for the CB1 and CB2 Cannabinoid Receptors and Metabolic Stability
  作者：Sonyuan Lin、Atmaram D. Khanolkar、Pusheng Fan、Andreas Goutopoulos、Ce Qin、Demetris Papahadjis、Alexandros Makriyannis

  DOI：10.1021/jm970257g

  日期：1998.12.1

  Several analogues of the endogenous cannabinoid receptor ligand arachidonylethanolamide (anandamide) were synthesized and evaluated in order to study (a) the structural requirements for high-affinity binding to the CB1 and CB2 cannabinoid receptors and (b) their hydrolytic stability toward anandamide amidase. The series reported here was aimed at exploring structure-activity relationships (SAR) primarily with regard to stereoelectronic requirements of ethanolamido headgroup for interaction with the cannabinoid receptor active site. Receptor affinities, reported as K-i values, were obtained by a standard receptor binding assay using [H-3]CP-55,940 as the radioligand, while stability toward the amidase was evaluated by comparing the K-i of each analogue in the presence and absence of phenylmethanesulfonyl fluoride (PMSF), a serine protease blocker and inhibitor of anandamide amidase. Introduction of a methyl group in the 1'- and 2'-positions or substitution of the ethanolamido headgroup with a butylamido group gave analogues with vastly improved biochemical stability. This is accomplished in some cases with increased receptor affinity. Conversely, oxazolyl and methyloxazolyl headgroups led to low-affinity analogues. Substitution of the hydroxyl group with electronegative substituents such as fluoro, chloro, allyl, and propargyl groups significantly increased receptor affinity but did not influence the biochemical stability. The 2'-chloro analogue of anandamide was found to have the highest affinity for CB1. Additionally, reversing the positions of the carbonyl and NH in the amido group produces retro-anandamides possessing considerably higher metabolic stability. Replacement of the arachidonyl tail with oleyl or linoleyl results in analogues with low affinities for both receptors. All of the analogues in this study showed high selectivity for the CB1 receptor over the peripheral CB2 receptor. The most potent analogues were tested for their ability to stimulate the binding of [S-35]GTP gamma S to G-proteins and were shown to be potent cannabimimetic agonists. The results are discussed in terms of pharmacophoric features affecting receptor affinity and enzymatic stability.
• Verwendung von Agonisten des zentralen Cannabinoid-Rezeptors CB1
  申请人：Bayer HealthCare AG

  公开号：EP0860168B1

  公开（公告）日：2007-08-08