6,7-dihydro-6-(2-methoxypropyl)-7-oxo-5H-2-pyridine-6-acetonitrile | 463304-04-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,7-dihydro-6-(2-methoxypropyl)-7-oxo-5H-2-pyridine-6-acetonitrile
• 英文别名: 2-[6-(3-methoxypropyl)-7-oxo-5H-cyclopenta[c]pyridin-6-yl]acetonitrile
• CAS: 463304-04-3
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: AUYGGWBTYRDXQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-dihydro-6-(2-methoxypropyl)-7-oxo-5H-2-pyridine-6-acetonitrile 在 Raney-Co 氢气 作用下， 以 甲醇 为溶剂， 50.0 ℃ 、620.54 kPa 条件下， 反应 18.0h， 生成 (+/-)-[4aα,9bβ]-2H-1,4a-ethano-3,4,5,9b-tetrahydro1H-cyclopenta[2,1-b:3,4-c']dipyridine
  参考文献：
  名称：

  Conformationally Constrained Nicotines:  Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor

  摘要：

  A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [H-3]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K-i = 4.79 nM) but also significant enantioselectivity over its antipode (K-i = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.

  DOI：

  10.1021/jm020916b
• 作为产物：
  描述：

  3-bromopyridinium ethylformate chloride 在 正丁基锂 、 lithium chloride 、 锌 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 74.5h， 生成 6,7-dihydro-6-(2-methoxypropyl)-7-oxo-5H-2-pyridine-6-acetonitrile
  参考文献：
  名称：

  Conformationally Constrained Nicotines:  Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor

  摘要：

  A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [H-3]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K-i = 4.79 nM) but also significant enantioselectivity over its antipode (K-i = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.

  DOI：

  10.1021/jm020916b

文献信息

• Conformationally Constrained Nicotines:  Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor
  作者：Thomas Ullrich、Sylvia Krich、Dieter Binder、Kurt Mereiter、David J. Anderson、Michael D. Meyer、Michael Pyerin

  DOI：10.1021/jm020916b

  日期：2002.8.1

  A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [H-3]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K-i = 4.79 nM) but also significant enantioselectivity over its antipode (K-i = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.