(2S,4aS,6aR,7R,9S,10aS,10bR)-9-(4-nitrobenzoyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1c]pyran-7-carboxylic acid methyl ester | 917506-27-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2S,4aS,6aR,7R,9S,10aS,10bR)-9-(4-nitrobenzoyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1c]pyran-7-carboxylic acid methyl ester
• 英文别名: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(furan-3-yl)-6a,10b-dimethyl-9-(4-nitrobenzoyl)oxy-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
• CAS: 917506-27-5
• 化学式: C₂₈H₂₉NO₁₀
• 分子量: 539.539
• InChiKey: AIYZBEMRHIYEJI-XAGHGKQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  155
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  SALVINORINB(品牌:CAYMAN进口) 、 4-硝基苯甲酰氯 在 4-二甲氨基吡啶 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到(2S,4aS,6aR,7R,9S,10aS,10bR)-9-(4-nitrobenzoyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1c]pyran-7-carboxylic acid methyl ester
  参考文献：
  名称：

  Herkinorin Analogues with Differential β-Arrestin-2 Interactions

  摘要：

  Salvinorin A is a psychoactive natural product that has been found to be a potent and selective kappa opioid receptor agonist in vitro and in vivo. The activity of salvinorin A is unusual compared to other opioids such as morphine in that it mediates potent kappa opioid receptor signaling yet leads to less receptor downregulation than observed with other kappa agonists. Our initial chemical modifications of salvinorin A have yielded one analogue, herkinorin (1c), with high affinity at the mu OR. We recently reported that 1c does not promote the recruitment of beta-arrestin-2 to the mu OR or receptor internalization. Here we describe three new derivatives of 1c (3c, 3f, and 3i) with similar properties and one, benzamide 7b, that promotes recruitment of beta-arrestin-2 to the mu OR and receptor internalization. When the important role mu opioid receptor regulation plays in determining physiological responsiveness to opioid narcotics is considered,mu opioids derived from salvinorin A may offer a unique template for the development of functionally selective mu opioid receptor-ligands with the ability to produce analgesia while limiting adverse side effects.

  DOI：

  10.1021/jm701162g

文献信息

• Synthetic Studies of Neoclerodane Diterpenes from <i>Salvia divinorum:</i> Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability
  作者：Rachel Saylor Crowley、Andrew P. Riley、Alexander M. Sherwood、Chad E. Groer、Nirajmohan Shivaperumal、Miguel Biscaia、Kelly Paton、Sebastian Schneider、Davide Provasi、Bronwyn M. Kivell、Marta Filizola、Thomas E. Prisinzano

  DOI：10.1021/acs.jmedchem.6b01235

  日期：2016.12.22

  Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due to associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia and reduced opioid-induced side effects. This compound, kurkinorin (5), is a potent and selective μ-opioid receptor (MOR) agonist (EC50 = 1.2 nM, >8000 μ/κ selectivity). 5 is a biased

  阿片类药物被广泛用于治疗数百万的痛苦患者，但由于相关的副作用，其止痛作用受到限制。在这里，我们报告显示出止痛和减少的阿片类药物引起的副作用的化学探针的发展和评估。这种化合物，kurkinorin（5）是一种有效的选择性μ阿片受体（MOR）激动剂（EC 50 = 1.2 nM，选择性> 8000μ/κ）。图5是MOR诱导的G蛋白信号转导于β-arrestin-2募集的偏向活化剂。对5 '与MOR晶体结构结合的动力学研究表明，从能量学角度出发，优选的结合方式不同于晶体配体。5的体内研究证明了中枢介导的抗伤害感受，显着降低了奖励效果，耐受性和镇静作用。我们建议，这种新型的MOR激动剂可能代表从其副作用中区分参与MOR诱导的镇痛的途径的有价值的工具。
• Herkinorin Analogues with Differential β-Arrestin-2 Interactions
  作者：Kevin Tidgewell、Chad E. Groer、Wayne W. Harding、Anthony Lozama、Matthew Schmidt、Alfred Marquam、Jessica Hiemstra、John S. Partilla、Christina M. Dersch、Richard B. Rothman、Laura M. Bohn、Thomas E. Prisinzano

  DOI：10.1021/jm701162g

  日期：2008.4.1

  Salvinorin A is a psychoactive natural product that has been found to be a potent and selective kappa opioid receptor agonist in vitro and in vivo. The activity of salvinorin A is unusual compared to other opioids such as morphine in that it mediates potent kappa opioid receptor signaling yet leads to less receptor downregulation than observed with other kappa agonists. Our initial chemical modifications of salvinorin A have yielded one analogue, herkinorin (1c), with high affinity at the mu OR. We recently reported that 1c does not promote the recruitment of beta-arrestin-2 to the mu OR or receptor internalization. Here we describe three new derivatives of 1c (3c, 3f, and 3i) with similar properties and one, benzamide 7b, that promotes recruitment of beta-arrestin-2 to the mu OR and receptor internalization. When the important role mu opioid receptor regulation plays in determining physiological responsiveness to opioid narcotics is considered,mu opioids derived from salvinorin A may offer a unique template for the development of functionally selective mu opioid receptor-ligands with the ability to produce analgesia while limiting adverse side effects.