tert-butyl (1R,5S)-7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (1R,5S)-7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate
• 英文别名: (1R,5S)-tert-butyl 7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate；tert-butyl (1R,5S)-7-(imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate
• 化学式: C₁₆H₂₄N₄O₃
• 分子量: 320.392
• InChiKey: TXHFLWQHXQOBGI-BETUJISGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.04
• 重原子数：
  23.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  67.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,5S)-7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 异丙醇 、 乙腈 为溶剂， 反应 48.0h， 生成 (1R,5S)-3,7-diazabicyclo[3.3.1]nonan-3-yl(biphenyl-4-yl)methanone fumarate
  参考文献：
  名称：

  The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: The influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents

  摘要：

  3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for alpha 4 beta 2* were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for alpha 4 beta 2* possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.059
• 作为产物：
  描述：

  tert-butyl (1R,5S)-7-benzyl-9-oxo-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate 在 hydrazine hydrate 、 5%-palladium/activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二乙二醇 为溶剂， 20.0~140.0 ℃ 、68.95 kPa 条件下， 反应 16.0h， 生成 tert-butyl (1R,5S)-7-(1H-imidazole-1-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-carboxylate
  参考文献：
  名称：

  The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: The influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents

  摘要：

  3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for alpha 4 beta 2* were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for alpha 4 beta 2* possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.059

文献信息

• The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor ligands. Part 2: Carboxamide derivatives with different spacer motifs
  作者：Christoph Eibl、Lenka Munoz、Isabelle Tomassoli、Clare Stokes、Roger L. Papke、Daniela Gündisch

  DOI：10.1016/j.bmc.2013.09.060

  日期：2013.12

  3,7-Diazabicyclo[3.3.1]nonane (bispidine) based nicotinic acetylcholine receptor (nAChR) ligands have been synthesized and evaluated for nAChRs interaction. Diverse spacer motifs were incorporated between the hydrogen bond acceptor (HBA) part and a variety of substituted (hetero)aryl moieties. Bispidine carboxamides bearing spacer motifs often showed high affinity in the low nanomolar range and selectivity for the alpha 4 beta 2* nAChR. Compounds 15, 25, and 47 with K-i values of about 1 nM displayed the highest affinities for alpha 4 beta 2* nAChR. All evaluated compounds are partial agonists or antagonists at alpha 4 beta 2*, with reduced or no effects on alpha 3 beta 4* with the exception of compound 15 (agonist), and reduced or no effect at alpha 7 and muscle subtypes. (C) 2013 Elsevier Ltd. All rights reserved.
• The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: The influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents
  作者：Christoph Eibl、Isabelle Tomassoli、Lenka Munoz、Clare Stokes、Roger L. Papke、Daniela Gündisch

  DOI：10.1016/j.bmc.2013.09.059

  日期：2013.12

  3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for alpha 4 beta 2* were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for alpha 4 beta 2* possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. (C) 2013 Elsevier Ltd. All rights reserved.