3-羟基-1-氮杂双环[2.2.2]辛烷-3-甲醇 | 61573-79-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: 3-羟基-1-氮杂双环[2.2.2]辛烷-3-甲醇
• 英文名称: 3-hydroxy-3-(hydroxymethyl)-1-azabicyclo<2.2.2>octane
• 英文别名: 3-hydroxymethyl-3-quinuclidinol；3-(Hydroxymethyl)-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 61573-79-3
• 化学式: C₈H₁₅NO₂
• 分子量: 157.213
• InChiKey: QHOANVQGVBKRAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-羟基-1-氮杂双环[2.2.2]辛烷-3-甲醇 、 2,2-二甲氧基丙烷 在 硫酸 作用下， 以 丙酮 为溶剂， 以36%的产率得到2,2-dimethyl spiro (1,3-dioxolane-4,3') quinuclidine
  参考文献：
  名称：

  Analogs of the muscarinic agent 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane]: synthesis and pharmacology

  摘要：

  A number of tetrahydrofuran analogues of 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] (1) have been prepared with the aim to obtain information about the relative importance of each of the oxygens in 1 for efficacy and for selectivity. In addition, the dimethyl and desmethyl analogues of 1 were prepared. The new compounds were compared to cis- and trans-1 with regard to their ability to displace (-)-[H-3]-3-quinuclidinyl benzilate ((-)-[H-3] QNB) from muscarinic receptors in cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs. Functioinal studies were made on isolated guinea pig bladder and ileum. The new compounds exhibited both lower affinity and efficacy than cis-1. A conformational study was performed, and the effects of steric and electronic factors on the biological activity of the compounds are discussed.

  DOI：

  10.1021/jm00087a007
• 作为产物：
  描述：

  螺[1-氮杂双环[2.2.2]辛烷-3,2'-环氧乙烷] 在 高氯酸 作用下， 反应 18.0h， 以48%的产率得到3-羟基-1-氮杂双环[2.2.2]辛烷-3-甲醇
  参考文献：
  名称：

  (−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘-oxazolidin-2‘-one], a Conformationally Restricted Analogue of Acetylcholine, Is a Highly Selective Full Agonist at the α7 Nicotinic Acetylcholine Receptor

  摘要：

  Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha7 nicotinic receptor, which is highly selective for the rat alpha7 nicotinic receptor over the alpha4 beta2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha7 nicotinic receptor affinity.

  DOI：

  10.1021/jm000249r

文献信息

• Spiro (1,3-dioxolane-4,3') quinuclidine compounds
  申请人：The Purdue Frederick Company

  公开号：US04104397A1

  公开（公告）日：1978-08-01

  Novel spiro (1,3-dioxolane-4,3') quinuclidine compounds of the formula ##STR1## wherein R.sub.1 and R.sub.2, which may be identical or different, each designates a member of the group hydrogen, alkyl or aryl; a process for the production of these and pharmaceutical compositions of matter containing such compound as active ingredient.

  新型螺环(1,3-二氧六环-4,3')喹诺啡类化合物，其化学式为##STR1##其中R.sub.1和R.sub.2，可能相同也可能不同，分别代表羟基、烷基或芳基；一种制备这些化合物的方法以及含有该化合物作为活性成分的药物组合物。
• US4104397A
  申请人：——

  公开号：US4104397A

  公开（公告）日：1978-08-01
• (−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘-oxazolidin-2‘-one], a Conformationally Restricted Analogue of Acetylcholine, Is a Highly Selective Full Agonist at the α7 Nicotinic Acetylcholine Receptor
  作者：George Mullen、James Napier、Michael Balestra、Thomas DeCory、Gregory Hale、John Macor、Robert Mack、James Loch、Ed Wu、Alexander Kover、Patrick Verhoest、Anthony Sampognaro、Eifion Phillips、Yanyi Zhu、Robert Murray、Ronald Griffith、James Blosser、David Gurley、Anthony Machulskis、John Zongrone、Alan Rosen、Jack Gordon

  DOI：10.1021/jm000249r

  日期：2000.11.1

  Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha7 nicotinic receptor, which is highly selective for the rat alpha7 nicotinic receptor over the alpha4 beta2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha7 nicotinic receptor affinity.
• Analogs of the muscarinic agent 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane]: synthesis and pharmacology
  作者：Gunnar Nordvall、Staffan Sundquist、Gunilla Glas、Adolf Gogoll、Lisbeth Nilvebrant、Uli Hacksell

  DOI：10.1021/jm00087a007

  日期：1992.5

  A number of tetrahydrofuran analogues of 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] (1) have been prepared with the aim to obtain information about the relative importance of each of the oxygens in 1 for efficacy and for selectivity. In addition, the dimethyl and desmethyl analogues of 1 were prepared. The new compounds were compared to cis- and trans-1 with regard to their ability to displace (-)-[H-3]-3-quinuclidinyl benzilate ((-)-[H-3] QNB) from muscarinic receptors in cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs. Functioinal studies were made on isolated guinea pig bladder and ileum. The new compounds exhibited both lower affinity and efficacy than cis-1. A conformational study was performed, and the effects of steric and electronic factors on the biological activity of the compounds are discussed.