(1R)-2-(2-pyrazinyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid ethyl ester | 389573-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (1R)-2-(2-pyrazinyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid ethyl ester
• CAS: 389573-43-7
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: RQNOVHXMACOVOX-ZWNOBZJWSA-N

物化性质

• 沸点：
  405.3±45.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.32
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R)-2-(2-pyrazinyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid ethyl ester 在 碘代三甲硅烷 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以87%的产率得到(1R)-2-(2-pyrazinyl)-8-azabicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Synthesis and evaluation of diazine containing bioisosteres of (−)-ferruginine as ligands for nicotinic acetylcholine receptors

  摘要：

  In this structure-affinity relationship (SAFIR) study, the bioisosteric potential of diazines in the field of ferruginine- type nAChR ligands was investigated. Novel enantiopure analogues of (-)-Ferruginine (3) such as 6 8 were synthesized utilizing enantiomerically pure N-protected (+)-2-tropanone 9 from the 'chiral pool' as versatile chiral building block and a palladium-catalyzed Stille cross-coupling of the tributylstannyl diazines 12, 14 and 16 with the vinyl triflate I I of ( +)-2-tropanone 9. The structures of the novel diazine analogues 6 8 of (-)-ferruginine (3) were assigned on the basis of spectral data, that of ligand 7 being additionally verified by X-ray crystallography. The bioisosteric replacement of the acetyl moiety as structural part of the lead compound 3 with the pyridazine, pyrimidine and pyrazine nucleus resulted in ligands with high to moderate affinity for the central alpha4 beta2 and remarkably low affinity for the alpha7* nAChR subtypes. Among the compounds synthesized and tested, 7 was the most active one with K-i = 3.7 nM (alpha4 beta2). Compared with the lead 3, this value represents a 30-fold improvement in the affinity for the alpha4 beta2 subtype combined with a substantially improved selectivity ratio between the alpha4 beta2 and alpha7* subtypes. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00188-2
• 作为产物：
  描述：

  (1R,5S)-8-ethoxycarbonyl-8-azabicyclo[3.2.1]octan-2-one 在 lithium chloride copper(l) iodide 、 二(氰基苯)二氯化钯 、 三苯胂 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 14.67h， 生成 (1R)-2-(2-pyrazinyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and evaluation of diazine containing bioisosteres of (−)-ferruginine as ligands for nicotinic acetylcholine receptors

  摘要：

  In this structure-affinity relationship (SAFIR) study, the bioisosteric potential of diazines in the field of ferruginine- type nAChR ligands was investigated. Novel enantiopure analogues of (-)-Ferruginine (3) such as 6 8 were synthesized utilizing enantiomerically pure N-protected (+)-2-tropanone 9 from the 'chiral pool' as versatile chiral building block and a palladium-catalyzed Stille cross-coupling of the tributylstannyl diazines 12, 14 and 16 with the vinyl triflate I I of ( +)-2-tropanone 9. The structures of the novel diazine analogues 6 8 of (-)-ferruginine (3) were assigned on the basis of spectral data, that of ligand 7 being additionally verified by X-ray crystallography. The bioisosteric replacement of the acetyl moiety as structural part of the lead compound 3 with the pyridazine, pyrimidine and pyrazine nucleus resulted in ligands with high to moderate affinity for the central alpha4 beta2 and remarkably low affinity for the alpha7* nAChR subtypes. Among the compounds synthesized and tested, 7 was the most active one with K-i = 3.7 nM (alpha4 beta2). Compared with the lead 3, this value represents a 30-fold improvement in the affinity for the alpha4 beta2 subtype combined with a substantially improved selectivity ratio between the alpha4 beta2 and alpha7* subtypes. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00188-2