N-(3-pyridyl)methyl-7-azabicyclo[2.2.1]heptane

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(3-pyridyl)methyl-7-azabicyclo[2.2.1]heptane
• 英文别名: 7-[(Pyridin-3-yl)methyl]-7-azabicyclo[2.2.1]heptane；7-(pyridin-3-ylmethyl)-7-azabicyclo[2.2.1]heptane
• 化学式: C₁₂H₁₆N₂
• 分子量: 188.272
• InChiKey: SCDKHPSUXHBJDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  7-氮杂双环[2,2,1]庚烷盐酸盐 在 10percent Pd/C 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 N-(3-pyridyl)methyl-7-azabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis and Biological Evaluation at Nicotinic Acetylcholine Receptors of N-Arylalkyl- and N-Aryl-7-Azabicyclo[2.2.1]heptanes

  摘要：

  A new series of N-arylalkyl-substituted 7-azabicyclo[2.2.1]heptanes and N-aryl-substituted 7-azabicyclo[2.2.1]heptanes were synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors. The in vitro binding affinities (K-i) of the 7-azabicyclo[2.2.1]heptane derivatives were measured by inhibition of [H-3]cytisine binding to rat brain tissue. The most potent ligand of the series was found to be N-(3-pyridylmethyl)-7-azabicyclo[2.2.1]heptane (5b, K-i = 98 nM). The chloro analogue (5a, K-i = 245 nM) 5a and epibatidine (1) produced dose-dependent analgesia in both hotplate and tail-flick tests when administered subcutaneously. However, when compounds 1 and 5a,b were administered intrathecally, all produced analgesia in the tail-flick test but only 5a produced analgesia in the hotplate test.

  DOI：

  10.1021/jm0103561

文献信息

• 7-Azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2 (σ2) receptor ligands
  作者：Samuel D. Banister、Louis M. Rendina、Michael Kassiou

  DOI：10.1016/j.bmcl.2012.04.077

  日期：2012.6

  A series of N-substituted 7-azabicyclo[2.2.1]heptanes (12–17 and 22–25) and similarly substituted pyrrolidines (32–36 and 41–44) were synthesized as sterically-reduced, achiral analogs of adamantane- and trishomocubane-derived σ ligands. In vitro competition binding assays against σ receptors revealed that arylalkyl N-substituents conferred selectivity for the σ2 subtype, while alicyclic or polycarbocyclic

  合成了一系列的N-取代的7-氮杂双环[2.2.1]庚烷（12 – 17和22 – 25）和类似取代的吡咯烷（32 – 36和41 – 44），它们是经空间还原的金刚烷-和-的非手性类似物。从三栖古猿衍生的σ配体。体外竞争对σ受体结合测定法揭示的σ该芳基烷基的N-取代基赋予选择性2亚型，而脂环或多碳取代基赋予高亲和力对两种亚型。所述σ 2个的结合和选择性亚型Ñ-芳基烷基-7-氮杂降冰片烷通常比类似取代的吡咯烷大，这表明氮原子周围的空间体积和构象限制对亚型的识别很重要。
• Synthesis and Biological Evaluation at Nicotinic Acetylcholine Receptors of <i>N</i>-Arylalkyl- and <i>N</i>-Aryl-7-Azabicyclo[2.2.1]heptanes
  作者：Jie Cheng、Chunming Zhang、Edwin D. Stevens、Sari Izenwasser、Dean Wade、Shaoyi Chen、Dennis Paul、Mark L. Trudell

  DOI：10.1021/jm0103561

  日期：2002.7.1

  A new series of N-arylalkyl-substituted 7-azabicyclo[2.2.1]heptanes and N-aryl-substituted 7-azabicyclo[2.2.1]heptanes were synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors. The in vitro binding affinities (K-i) of the 7-azabicyclo[2.2.1]heptane derivatives were measured by inhibition of [H-3]cytisine binding to rat brain tissue. The most potent ligand of the series was found to be N-(3-pyridylmethyl)-7-azabicyclo[2.2.1]heptane (5b, K-i = 98 nM). The chloro analogue (5a, K-i = 245 nM) 5a and epibatidine (1) produced dose-dependent analgesia in both hotplate and tail-flick tests when administered subcutaneously. However, when compounds 1 and 5a,b were administered intrathecally, all produced analgesia in the tail-flick test but only 5a produced analgesia in the hotplate test.