(-)-N-propylnormorphine | 41590-60-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (-)-N-propylnormorphine
• 英文别名: N-n-propylnormorphine；(4R,4aR,7S,7aR,12bS)-3-propyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol
• CAS: 41590-60-7
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: NXJPPUHGGHXXJJ-SSTWWWIQSA-N

物化性质

• 熔点：
  244-245 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  494.0±45.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  52.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-N-propylnormorphine 在 palladium on activated charcoal copper(l) iodide 、 甲烷磺酸 、 氢气 、 碘 、 silver trifluoroacetate 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醚 、 氯仿 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 25.0~95.0 ℃ 、310.27 kPa 条件下， 反应 74.5h， 生成 (R)-(-)-8,11-dimethoxy-N-n-propylnoraporphine
  参考文献：
  名称：

  5-HT 1A受体拮抗作用：（R）-（-）-8，11-二甲氧基诺拉啡的N-烷基衍生物。

  摘要：

  以前的发现提示，芳环上的对二甲氧基取代模式可在某些环系统中保留多巴胺能激动剂效应，其中邻苯二酚衍生物是有效的多巴胺能激动剂，将8,11-二甲氧基取代模式引入了Aph环中。在阿扑吗啡中的10,11-二羟基部分的位置。适当的吗啡衍生物的酸催化重排为阿福啡环系统提供了6a不对称中心立体化学完整性的保留。通过催化氢解其苯基四唑基醚除去位置10处的羟基。用三氟乙酰基亚硫酸氢盐在8位以高收率碘化所得的11-羟基阿扑吗啡的甲基醚。这是合成碘化的海豚碱衍生物的第一个说明。通过与甲醇钠和碘化亚铜反应，将8-碘取代基替换为甲氧基。N-甲基靶标化合物7或Nn-丙基衍生物8均未显示出多巴胺能或血清素能激动作用。但是，有7种药物具有受体结合特性和其他药理特性，表明它可能是5-HT1A受体拮抗剂。

  DOI：

  10.1021/jm00128a044
• 作为产物：
  描述：

  吗啡 在 sodium thiophenolate 作用下， 以 氯仿 、 乙腈 、 丁酮 为溶剂， 反应 78.0h， 生成 (-)-N-propylnormorphine
  参考文献：
  名称：

  A Convenient Method for Replacing theN-Methyl Group of Morphine, Codeine, and Thebaine by Other Alkyl Groups

  摘要：

  DOI：

  10.1055/s-1983-30523

文献信息

• Aporphines. 42. Synthesis of (R)-(-)-11-hydroxyaporphines
  作者：Vishnu J. Ram、John L. Neumeyer

  DOI：10.1021/jo00143a050

  日期：1982.10
• Determination of neutral manufacturing impurities in heroin by capillary gas chromatography with electron capture detection after reduction with lithium aluminum hydride and derivatization with heptafluorobutyric anhydride
  作者：James M. Moore、Andrew C. Allen、Donald A. Cooper

  DOI：10.1021/ac00297a005

  日期：1986.5.1
• Madyastha; Reddy; Sridhar, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1998, vol. 37, # 8, p. 749 - 753
  作者：Madyastha、Reddy、Sridhar

  DOI：——

  日期：——
• Hosztafi; Makleit, Pharmazie, 1994, vol. 49, # 7, p. 530 - 531
  作者：Hosztafi、Makleit

  DOI：——

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

  DOI：10.1021/jm960188q

  日期：1996.1.1

  Derivatives of the selective serotonin 5-HT1A receptor agonist (R)-11-hydroxy-10-methylaporphine (2) having various substituents in the C10-position or at the nitrogen have been synthesized from natural morphine or 6-O-acetylcodeine, respectively. The C10-substituents were introduced using efficient Stille or Suzuki cross-coupling reactions. The compounds were evaluated for their affinities to 5-HT1A and dopamine (DA) D-1 and D-2A receptors in vitro. All compounds tested displayed low (micromolar) affinities to D-1 and D-2A receptors. In addition, changes in steric bulk and/or electronic properties of the C10-substituent as compared to a C10-methyl group, as well as substitution of the N-methyl group for a hydrogen or a larger N-alkyl group, produced a marked decrease in the affinities to 5-HT1A receptors. Selected compounds that displayed moderate to high affinities to 5-HT1A receptors were evaluated for their ability to stimulate 5-HT1A receptors in vivo. The evaluated compounds behaved as agonists at 5-HT1A receptors, except for the N-propyl analogue of 2, (R)-11-hydroxy-10-methyl-N-propylnoraporphine (23), which displayed weak DA receptor agonism at the doses tested. Hence, the substitution pattern of 2 (a C10-methyl, a C11-hydroxy, and an N-methyl group) appears to be optimal for potent interaction of 10,11-disubstituted (R)-aporphines with 5-HT1A receptors. Modeling of ligand-5-HT1A receptor interactions was performed in an attempt to rationalize the observed affinity data. The binding site model suggests the presence of a ''methyl pocket'' in the 5-HT1A receptor binding site. The C11-methoxy-substituted aporphines appear to have a different binding mode compared to 2, implying a different accessibility of these compounds to the ''methyl pocket''.