1-methyl-2,6-di-naphthalen-1-yl-4-oxo-piperidine-3,5-dicarboxylic acid dimethyl ester | 40328-63-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-methyl-2,6-di-naphthalen-1-yl-4-oxo-piperidine-3,5-dicarboxylic acid dimethyl ester
• 英文别名: Dimethyl 1-methyl-2,6-dinaphthalen-1-yl-4-oxopiperidine-3,5-dicarboxylate
• CAS: 40328-63-0
• 化学式: C₃₀H₂₇NO₅
• 分子量: 481.548
• InChiKey: ONOWKJQLBAFCSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 1-methyl-2,6-di-naphthalen-1-yl-4-oxo-piperidine-3,5-dicarboxylic acid dimethyl ester 、 甲胺 以 甲醇 、 水 为溶剂， 生成 (1R,2R,4S,5S)-3,7-Dimethyl-2,4-di-naphthalen-1-yl-9-oxo-3,7-diaza-bicyclo[3.3.1]nonane-1,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Synthesis and Opioid Receptor Affinity of a Series of 2,4-Diaryl-Substituted 3,7-Diazabicylononanones

  摘要：

  3,7-Diazabicyclo[3.3.1]nonan-9-ones having aryl rings in positions 2 and 4 with systematically varied substituents were synthesized using a double Mannich procedure. Radioligand binding assays were performed to measure the affinity of the compounds to the mu-, delta-, and kappa-opioid receptors. The affinity of all 2,4-diphenyl-substituted 3,7-diazabicyclo[3.3.1]nonan-9-ones to the mu- and delta-receptors was found to be low. In contrast, with exception of the nitro- and cyanophenyl-substituted compounds, most of the diazabicycles showed considerable affinity for the kappa-receptor. In particular, the m-fluoro-, p-methoxy-, and m-hydroxy-substituted compounds have an affinity in the submicromolar range. Due to solubility problems in aqueous media, salts of HZ2 were synthesized. The methiodide shows high kappa-affinity and may, thus, be a promising candidate for development of a peripheral kappa-agonist, e.g. for use in the case of rheumatoid arthritis.

  DOI：

  10.1021/jm0009484
• 作为产物：
  描述：

  1,3-丙酮二羧酸二甲酯 、 1-萘甲醛 、 甲胺 以 甲醇 为溶剂， 反应 12.0h， 生成 1-methyl-2,6-di-naphthalen-1-yl-4-oxo-piperidine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  κ-激动性3,7-二氮杂双环[3.3.1] nonan-9-ones的构象和构型行为—合成，核磁共振研究和半经验PM3计算

  摘要：

  发现2，4-二芳基取代的3，7-二氮杂双环[3.3.1]壬南-9-1，1，5-二酯对κ-阿片样物质受体具有高亲和力。为了开发高效的止痛药，本研究的目的是新型2,4-双（4-硝基苯基），2,4-双（3-硝基苯基），2,4-双（4）的合成和结构表征-喹啉基），2,4-双（2-喹啉基），2,4-双（1-萘基）和2,4-双（2-萘基）取代的3,7-二氮杂双环[3.3.1] nonan-9 NMR光谱法和分子建模的方法，得到一个1，5-二酯。可以证明，几种衍生物经历反式-顺式连接到刚性骨架上的芳环的-异构化，而另一些则显示出旋转异构化。进行了半经验的量子化学PM3计算，以分析异构体的热力学稳定性以及反式-顺式-或顺式-反式转化的机理。

  DOI：

  10.1039/a806641h

文献信息

• Conformational and configurational behaviour of κ-agonistic 3,7-diazabicyclo[3.3.1]nonan-9-ones—synthesis, nuclear magnetic resonance studies and semiempirical PM3 calculations
  作者：Tom Siener、Ulrike Holzgrabe、Susanne Drosihn、Wolfgang Brandt

  DOI：10.1039/a806641h

  日期：——

  7-diazabicyclo[3.3.1]nonan-9-one 1,5-diesters were found to have a high affinity for κ-opioid receptors. To develop highly potent analgesics, the purpose of this study was the synthesis and the structural characterisation of the novel 2,4-bis(4-nitrophenyl), 2,4-bis(3-nitrophenyl), 2,4-bis(4-quinolyl), 2,4-bis(2-quinolyl), 2,4-bis(1-naphthyl) and 2,4-bis(2-naphthyl) substituted 3,7-diazabicyclo[3.3.1]nonan-9-one

  发现2，4-二芳基取代的3，7-二氮杂双环[3.3.1]壬南-9-1，1，5-二酯对κ-阿片样物质受体具有高亲和力。为了开发高效的止痛药，本研究的目的是新型2,4-双（4-硝基苯基），2,4-双（3-硝基苯基），2,4-双（4）的合成和结构表征-喹啉基），2,4-双（2-喹啉基），2,4-双（1-萘基）和2,4-双（2-萘基）取代的3,7-二氮杂双环[3.3.1] nonan-9 NMR光谱法和分子建模的方法，得到一个1，5-二酯。可以证明，几种衍生物经历反式-顺式连接到刚性骨架上的芳环的-异构化，而另一些则显示出旋转异构化。进行了半经验的量子化学PM3计算，以分析异构体的热力学稳定性以及反式-顺式-或顺式-反式转化的机理。
• Synthesis and Opioid Receptor Affinity of a Series of 2,4-Diaryl-Substituted 3,7-Diazabicylononanones
  作者：Tom Siener、Antonella Cambareri、Ulrich Kuhl、Werner Englberger、Michael Haurand、Babette Kögel、Ulrike Holzgrabe

  DOI：10.1021/jm0009484

  日期：2000.10.1

  3,7-Diazabicyclo[3.3.1]nonan-9-ones having aryl rings in positions 2 and 4 with systematically varied substituents were synthesized using a double Mannich procedure. Radioligand binding assays were performed to measure the affinity of the compounds to the mu-, delta-, and kappa-opioid receptors. The affinity of all 2,4-diphenyl-substituted 3,7-diazabicyclo[3.3.1]nonan-9-ones to the mu- and delta-receptors was found to be low. In contrast, with exception of the nitro- and cyanophenyl-substituted compounds, most of the diazabicycles showed considerable affinity for the kappa-receptor. In particular, the m-fluoro-, p-methoxy-, and m-hydroxy-substituted compounds have an affinity in the submicromolar range. Due to solubility problems in aqueous media, salts of HZ2 were synthesized. The methiodide shows high kappa-affinity and may, thus, be a promising candidate for development of a peripheral kappa-agonist, e.g. for use in the case of rheumatoid arthritis.