tetrahydro-2H-pyran-2-ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate

• 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: tetrahydro-2H-pyran-2-ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
• 英文别名: oxan-2-ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
• 化学式: C₂₆H₄₂O₃
• 分子量: 402.618
• InChiKey: ZQIZHDKTSINYDM-DOFZRALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  29
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  四氢吡喃-2-甲醇 、 花生四烯酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以29%的产率得到tetrahydro-2H-pyran-2-ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
  参考文献：
  名称：

  Structure−Activity Relationship of a Series of Inhibitors of Monoacylglycerol HydrolysisComparison with Effects upon Fatty Acid Amide Hydrolase

  摘要：

  A series of 32 heterocyclic analogues based on the structure of 2-arachidonoylglycerol (2-AG) were synthesized and tested for their ability to inhibit monoacylglycerol lipase and fatty acid an-tide hydrolase activities. The designed compounds feature a hydrophobic moiety and different heterocyclic subunits that mimic the glycerol fragment. This series has allowed us to carry out the first systematic structure activity relationship study on inhibition of 2-AG hydrolysis. The most promising compounds were oxiran-2-ylmethyl (5Z,8Z,l 11Z,14Z)-icosa-5,8,11,14-tetraenoate (1) and tetrahydro-2H-pyran-2-ylmethyl (5Z,8Z,11Z,14z)-icosa5,8,11,14-tetraenoate (5). They inhibited cytosolic 2-oleoylglycerol (2-OG) hydrolysis completely (IC50 values of 4.5 and 5.6 mu M, respectively). They also blocked, albeit less potently, 2-OG hydrolysis in membrane fractions (IC50 values of 19 and 26,mu M, respectively) and anandamide hydrolysis (IC50 values of 12 and 51 mu M, respectively). These compounds will be useful in delineating the importance of the cytosolic hydrolytic activity in the regulation of 2-AG levels and, hence, its potential as a target for drug development.

  DOI：

  10.1021/jm070642y

文献信息

• Structure−Activity Relationship of a Series of Inhibitors of Monoacylglycerol HydrolysisComparison with Effects upon Fatty Acid Amide Hydrolase
  作者：José Antonio Cisneros、Séverine Vandevoorde、Silvia Ortega-Gutiérrez、Clément Paris、Christopher J. Fowler、María L. López-Rodríguez

  DOI：10.1021/jm070642y

  日期：2007.10.1

  A series of 32 heterocyclic analogues based on the structure of 2-arachidonoylglycerol (2-AG) were synthesized and tested for their ability to inhibit monoacylglycerol lipase and fatty acid an-tide hydrolase activities. The designed compounds feature a hydrophobic moiety and different heterocyclic subunits that mimic the glycerol fragment. This series has allowed us to carry out the first systematic structure activity relationship study on inhibition of 2-AG hydrolysis. The most promising compounds were oxiran-2-ylmethyl (5Z,8Z,l 11Z,14Z)-icosa-5,8,11,14-tetraenoate (1) and tetrahydro-2H-pyran-2-ylmethyl (5Z,8Z,11Z,14z)-icosa5,8,11,14-tetraenoate (5). They inhibited cytosolic 2-oleoylglycerol (2-OG) hydrolysis completely (IC50 values of 4.5 and 5.6 mu M, respectively). They also blocked, albeit less potently, 2-OG hydrolysis in membrane fractions (IC50 values of 19 and 26,mu M, respectively) and anandamide hydrolysis (IC50 values of 12 and 51 mu M, respectively). These compounds will be useful in delineating the importance of the cytosolic hydrolytic activity in the regulation of 2-AG levels and, hence, its potential as a target for drug development.