(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid ((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methylamide) | 1115860-30-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid ((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methylamide)
• 英文别名: Arachidonoyl-4-methylaminoantipyrin；4-[(arachidonoyl)(methyl)amino]antipyrin；(5Z,8Z,11Z,14Z)-N-(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-N-methylicosa-5,8,11,14-tetraenamide
• CAS: 1115860-30-4
• 化学式: C₃₂H₄₅N₃O₂
• 分子量: 503.728
• InChiKey: HJUXEQPTXUOUOQ-SNPVRQPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  花生四烯酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 1.25h， 生成 (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid ((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methylamide)
  参考文献：
  名称：

  Novel bioactive metabolites of dipyrone (metamizol)

  摘要：

  Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB1 and CB2) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.028

文献信息

• Effects of metabolites of the analgesic agent dipyrone (metamizol) on rostral ventromedial medulla cell activity in mice
  作者：Sabatino Maione、Lilyana Radanova、Danilo De Gregorio、Livio Luongo、Luciano De Petrocellis、Vincenzo Di Marzo、Peter Imming

  DOI：10.1016/j.ejphar.2014.12.022

  日期：2015.2

  The molecular mechanism of action of dipyrone, a widely used antipyretic and non-opioid analgesic drug, is still not fully understood. Actions upon peripheral inflamed tissues as well as the central nervous system, especially upon the PAG-RVM axis, have been suggested. Dipyrone is a prod rug and its activity is due to its immediate conversion to its active metabolites. We tested the effect of two recently discovered metabolites of dipyrone, the arachidonoyl amides of 4-methylaminoantipyrine and 4-aminoantipyrine, on the neurons of the rostral ventromedial medulla (RVM), which are part of the descending pathway of antinociception. These compounds reduced the activity of ON-cells and increased the activity of OFF-cells. Both CB1 and TRPV1 blockade reversed these effects, suggesting that the endocannabinoid/endovanilloid system takes part in the analgesic effects of dipyrone. (C) 2015 Published by Elsevier B.V.
• Novel bioactive metabolites of dipyrone (metamizol)
  作者：Tobias Rogosch、Christian Sinning、Agnes Podlewski、Bernhard Watzer、Joel Schlosburg、Aron H. Lichtman、Maria G. Cascio、Tiziana Bisogno、Vincenzo Di Marzo、Rolf Nüsing、Peter Imming

  DOI：10.1016/j.bmc.2011.11.028

  日期：2012.1

  Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB1 and CB2) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain. (C) 2011 Elsevier Ltd. All rights reserved.