S-alpha-methylanandamide

• 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: S-alpha-methylanandamide
• 英文别名: (S)-(-)-arachidonyl-1'-hydroxy-2'propylamide；S1-methanandamide；(-)-Methanandamide；S-1 Methanandamide；(5Z,8Z,11Z,14Z)-N-[(2S)-1-hydroxypropan-2-yl]icosa-5,8,11,14-tetraenamide
• 化学式: C₂₃H₃₉NO₂
• 分子量: 361.568
• InChiKey: SQKRUBZPTNJQEM-AQNSPSBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  花生四烯酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 草酰氯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 1.25h， 生成 S-alpha-methylanandamide
  参考文献：
  名称：

  (R)-Methanandamide: A Chiral Novel Anandamide Possessing Higher Potency and Metabolic Stability

  摘要：

  Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas deferens. The lead analog was also tested for its potency in. vivo. Of the analogs tested, (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide [(R)-methanandamide] exhibited the highest affinity for the cannabinoid receptor with a K-i of 20 +/- 1.6 nM, 4-fold lower than that of anandamide (K-i = 78 +/- 2 nM). Moreover, determination of the cannabinoid binding affinity in the presence and absence of the protease inhibitor phenylmethanesulfonyl fluoride (PMSF) revealed that (R)-methanandamide possesses a remarkable stability to aminopeptidase hydrolysis. Pharmacological studies on mouse isolated vasa deferentia demonstrated that all four analogs produce concentration-related inhibition of the twitch response and the order of potency is the same as the rank order of the affinities of these agonists for cannabinoid binding sites. Furthermore, experiments with mice have demonstrated that (R)-methanandamide also possesses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception.

  DOI：

  10.1021/jm00038a020

文献信息

• (R)-Methanandamide: A Chiral Novel Anandamide Possessing Higher Potency and Metabolic Stability
  作者：Vasiliki Abadji、Sonyuan Lin、Gihan Taha、Graeme Griffin、Lesley A. Stevenson、Roger G. Pertwee、Alexandros Makriyannis

  DOI：10.1021/jm00038a020

  日期：1994.6

  Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas deferens. The lead analog was also tested for its potency in. vivo. Of the analogs tested, (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide [(R)-methanandamide] exhibited the highest affinity for the cannabinoid receptor with a K-i of 20 +/- 1.6 nM, 4-fold lower than that of anandamide (K-i = 78 +/- 2 nM). Moreover, determination of the cannabinoid binding affinity in the presence and absence of the protease inhibitor phenylmethanesulfonyl fluoride (PMSF) revealed that (R)-methanandamide possesses a remarkable stability to aminopeptidase hydrolysis. Pharmacological studies on mouse isolated vasa deferentia demonstrated that all four analogs produce concentration-related inhibition of the twitch response and the order of potency is the same as the rank order of the affinities of these agonists for cannabinoid binding sites. Furthermore, experiments with mice have demonstrated that (R)-methanandamide also possesses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception.