(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(azido)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]-pyran-7-carboxylic acid methyl ester | 879090-22-9

• 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,4aR,6aR,7R,9S,10aS,10bR)-9-(azido)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]-pyran-7-carboxylic acid methyl ester
• 英文别名: 2-Salvinorinylazide；(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(Azido)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester；methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-azido-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
• CAS: 879090-22-9
• 化学式: C₂₁H₂₅N₃O₆
• 分子量: 415.446
• InChiKey: QAOFTRHADNMVGJ-CEFSSPBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  97.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(azido)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]-pyran-7-carboxylic acid methyl ester 在 氯化铵 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 以84%的产率得到2-aminosalvinorin
  参考文献：
  名称：

  Opioid receptor ligands and methods for their preparation

  摘要：

  该发明提供了公式I的新化合物，这些化合物是阿片受体配体。该发明还提供了包含这些化合物的药物组合物，以及通过向需要治疗的哺乳动物施用这些化合物来治疗与阿片受体功能相关的疾病的方法。该发明还提供了一种改进的方法，用于分离中间体材料，以获得公式I的化合物。

  公开号：

  US20060058264A1
• 作为产物：
  描述：

  Salvinorinyl-2-bromide 在 sodium azide 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以86%的产率得到(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(azido)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]-pyran-7-carboxylic acid methyl ester
  参考文献：
  名称：

  Opioid receptor ligands and methods for their preparation

  摘要：

  该发明提供了公式I的新化合物，这些化合物是阿片受体配体。该发明还提供了包含这些化合物的药物组合物，以及通过向需要治疗的哺乳动物施用这些化合物来治疗与阿片受体功能相关的疾病的方法。该发明还提供了一种改进的方法，用于分离中间体材料，以获得公式I的化合物。

  公开号：

  US20060058264A1

文献信息

• Opioid receptor ligands and methods for their preparation
  申请人：Prisinzano Thomas

  公开号：US20060058264A1

  公开（公告）日：2006-03-16

  The invention provides novel compounds of formula I: that are opioid receptor ligands. The invention also provides pharmaceutical compositions comprising such compounds as well as methods for treating diseases associated with opioid receptor function by administering such compounds to a mammal in need of treatment. The invention also provides an improved method for isolating intermediate materials useful for obtaining compounds of formula I.

  该发明提供了公式I的新化合物，这些化合物是阿片受体配体。该发明还提供了包含这些化合物的药物组合物，以及通过向需要治疗的哺乳动物施用这些化合物来治疗与阿片受体功能相关的疾病的方法。该发明还提供了一种改进的方法，用于分离中间体材料，以获得公式I的化合物。
• Synthesis and in vitro evaluation of salvinorin A analogues: Effect of configuration at C(2) and substitution at C(18)
  作者：Cécile Béguin、Michele R. Richards、Jian-Guo Li、Yulin Wang、Wei Xu、Lee-Yuan Liu-Chen、William A. Carlezon、Bruce M. Cohen

  DOI：10.1016/j.bmcl.2006.05.093

  日期：2006.9

  kappa-opioid receptor ligands have raised interest for their apparent effects on mood. The potent and selective kappa-agonist salvinorin A has short-lasting (15 min) depressive-like effects in rats in behavioral models used to study mood disorders. Two series of salvinorin derivatives modified at C(2) and C(18), respectively, were synthesized and their kappa-opioid receptor affinities, potencies, and efficacies were evaluated using in vitro receptor binding and biochemical functional assays. Modification at C(2) yielded potent kappa-agonists that are predicted to have improved metabolic stability (14a, 15a) or increased water solubility (10b). Our preliminary SAR study at C(18) suggested that this part of the molecule interacts with a tight lipophilic pocket of the K-receptor. (c) 2006 Elsevier Ltd. All rights reserved.
• Stewart, D. Jeremy; Fahmy, Hesham; Roth, Bryan L., Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 4, p. 269 - 275
  作者：Stewart, D. Jeremy、Fahmy, Hesham、Roth, Bryan L.、Yan, Feng、Zjawiony, Jordan K.

  DOI：——

  日期：——
• US7728001B2
  申请人：——

  公开号：US7728001B2

  公开（公告）日：2010-06-01
• 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.