(-)-(R)-11-hydroxy-10-methylaporphine | 111635-19-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (-)-(R)-11-hydroxy-10-methylaporphine
• 英文别名: (R)-(-)-10-methyl-11-hydroxyaporphine；(R)-11-hydroxy-10-methylaporphine；11-Hydroxy-10-methylaporphine；(6aR)-6,10-dimethyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol
• CAS: 111635-19-9
• 化学式: C₁₈H₁₉NO
• 分子量: 265.355
• InChiKey: YGOZTDLAUVOPMF-OAHLLOKOSA-N

物化性质

• 熔点：
  270-271 °C
• 沸点：
  440.2±33.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  硫酸吗啡 在 bis-triphenylphosphine-palladium(II) chloride 甲烷磺酸 、 三乙胺 、 三苯基膦 、 lithium chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (-)-(R)-11-hydroxy-10-methylaporphine
  参考文献：
  名称：

  R-(−)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands

  摘要：

  Several N-substituted-11-hydroxy-10-hydroxymethyl- and 11-hydroxy-10-methylaporphines were synthesized and their binding affinities at dopamine D, and D, receptors and serotonin 5-HT1A and 5-HT2A receptors in rat forebrain tissue were evaluated. Tested compounds displayed moderate to high affinity to 5-HT1A receptors but low affinity to D, and D-2 receptors. The most potent novel 5-HT1A agent was R-(-)-N-methyl-10-hydroxymethyl-11-hydroxyaporphine. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.057

文献信息

• Facile syntheses of aporphine derivatives
  作者：Martin H. Hedberg、Anette M. Johansson、Uli Hacksell

  DOI：10.1039/c39920000845

  日期：——

  New and efficient synthetic routes, utilizing palladium-catalysed reactions, provide (R)-11-hydroxy-10-methylaporphine 2 and (R)-11-hydroxyaporphine 3 from natural morphine 4.

  利用钯催化的反应的新的有效合成路线，从天然吗啡4提供（R）-11-羟基-10-甲基aporphine 2和（R）-11-羟基aporphine 3。
• Glycoside and orthoester glycoside derivatives of apomorphine, analogs, and uses thereof
  申请人：Holick Michael

  公开号：US20060004190A1

  公开（公告）日：2006-01-05

  Disclosed are glycoside and orthoester glycoside derivatives of apomorphine and analogs thereof to treat conditions and diseasessuch as erectile dysfunction.

  所公开的是阿朴吗啡的糖苷和原酯糖苷衍生物及其类似物，用于治疗勃起功能障碍等病症。
• R(-)-11-hydroxyaporphine derivatives and uses thereof
  申请人：Neumeyer L. John

  公开号：US20060040900A1

  公开（公告）日：2006-02-23

  The invention features derivatives of R(—)-11-hydroxyaporphines and methods of treating Parkinson's disease, sexual dysfunction, and depressive disorders therewith.

  本发明的特点是 R(-)-11-羟基阿扑啡的衍生物以及用其治疗帕金森病、性功能障碍和抑郁障碍的方法。
• (R)-11-Hydroxy- and (R)-11-Hydroxy-10-methylaporphine: Synthesis, Pharmacology, and Modeling of D2A and 5-HT1A Receptor Interactions
  作者：Martin H. Hedberg、Anette M. Johansson、Gunnar Nordvall、Ari Yliniemela、Hong Bing Li、Arnold R. Martin、Stephan Hjorth、Lena Unelius、Staffan Sundell、Uli Hacksell

  DOI：10.1021/jm00004a011

  日期：1995.2

  (R)-11-Hydroxyaporphine (2) and (R)-11-hydroxy-10-methylaporphine (3) were synthesized from natural morphine by using new, short, and efficient synthetic sequences. The dopaminergic and serotonergic effects of 2 and 3 were evaluated by use of in vitro and in vivo test systems. The results indicate that 3 is a potent, selective, and efficacious 6-HT1A receptor agonist. In contrast, 2 is a partial 5-HT1A receptor agonist of low potency which has affinity also for central D-1 and D-2A receptors. The differences in pharmacological profiles were rationalized by modeling of ligand-receptor interactions using homology-based receptor models of the 6-HT1A and D-2A receptor binding site. The selective and pronounced serotonergic effects of 3 appear to be due to the CIO-methyl group, which is accommodated by a lipophilic pocket in the 5-HT1A receptor. In contrast, the C10-methyl group of 3 is not accommodated by the binding site model of the D-2A receptor.
• (R)-(-)-10-Methyl-11-hydroxyaporphine: a highly selective serotonergic agonist
  作者：Joseph G. Cannon、Prem Mohan、Jacek Bojarski、John Paul Long、Ranbir K. Bhatnagar、Paul A. Leonard、Jan R. Flynn、Tapan K. Chatterjee

  DOI：10.1021/jm00397a007

  日期：1988.2

  Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.