(R)-6-Methyl-11-vinyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline | 765249-57-8

• 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)-6-Methyl-11-vinyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• 英文别名: (6aR)-11-ethenyl-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• CAS: 765249-57-8
• 化学式: C₁₉H₁₉N
• 分子量: 261.367
• InChiKey: YMOFDQWTDIMQMZ-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-6-Methyl-11-vinyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 (R)-11-Ethyl-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
  参考文献：
  名称：

  11-Substituted (R)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions

  摘要：

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].

  DOI：

  10.1021/jm960189i
• 作为产物：
  描述：

  (-)-11-Hydroxyaporphine 在 bis-triphenylphosphine-palladium(II) chloride 、 2,6-二叔丁基-4-甲基苯酚 、 potassium carbonate 、 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 75.0h， 生成 (R)-6-Methyl-11-vinyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
  参考文献：
  名称：

  11-Substituted (R)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions

  摘要：

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].

  DOI：

  10.1021/jm960189i

文献信息

• 11-Substituted (<i>R</i>)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions
  作者：Martin H. Hedberg、Tero Linnanen、Johanna M. Jansen、Gunnar Nordvall、Stephan Hjorth、Lena Unelius、Anette M. Johansson

  DOI：10.1021/jm960189i

  日期：1996.1.1

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].