3-(2-aminoethyl)quinuclidin-3-ol | 313643-37-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-(2-aminoethyl)quinuclidin-3-ol
• 英文别名: 3-(2-Aminoethyl)-1-azabicyclo[2.2.2]octan-3-ol；3-(2-aminoethyl)-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 313643-37-7
• 化学式: C₉H₁₈N₂O
• 分子量: 170.255
• InChiKey: RABZIAVTYJQJMS-UHFFFAOYSA-N

物化性质

• 沸点：
  281.1±15.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  49.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-aminoethyl)quinuclidin-3-ol 、 N-(6-methoxybenzo[d]thiazol-2-yl)-1H-imidazole-1-carbothioamide 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  设计和合成一系列新的4-杂芳基氨基-1'-氮杂螺[恶唑-5,3'-双环[2.2.2]辛烷作为α7烟碱受体激动剂。1.药理基团的发展与早期构效关系

  摘要：

  描述了一系列含喹核苷的螺杂恶唑烷（“螺酰胺化物”）的设计和合成及其作为α7烟碱型乙酰胆碱受体部分激动剂的用途。该系列的选定成员对α7的选择性优于高度同源的5-HT 3A受体。所述的修饰Ñ导致（1 -spiroimidate杂环取代基小号，2 - [R，4小号- ）ñ -异喹啉-3-基）-4' ħ -4-氮杂螺[二环[2.2.2]辛烷-2,5-'恶唑] -2'-胺（BMS-902483），一种有效的α7部分激动剂，可改善临床前啮齿动物模型的认知度。

  DOI：

  10.1021/acs.jmedchem.6b01506
• 作为产物：
  描述：

  3-奎宁环酮 在 lithium aluminium tetrahydride 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 19.0h， 生成 3-(2-aminoethyl)quinuclidin-3-ol
  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

• [EN] QUINUCLIDINE, 1-AZABICYCLO[2.2.1]HEPTANE, 1-AZABICYCLO [3.2.1]OCTANE, and 1-AZABICYCLO[3.2.2]NONANE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉS DE QUINUCLIDINE, 1-AZABICYCLO[2.2.1]HEPTANE, 1-AZABICYCLO [3.2.1]OCTANE, ET 1-AZABICYCLO[3.2.2]NONANE UTILES COMME LIGANDS DU RÉCEPTEUR ALPHA-7 NICOTINIQUE DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013177024A1

  公开（公告）日：2013-11-28

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  本公开提供I式化合物，包括其盐，以及使用该化合物的组合物和方法。这些化合物是尼古丁酸α7受体的配体，可用于治疗中枢神经系统的各种疾病，尤其是情感和神经退行性疾病。
• QUINUCLIDINE, 1-AZABICYCLO[2.2.1]HEPTANE, 1-AZABICYCLO [3.2.1]OCTANE, and 1-AZABICYCLO[3.2.2]NONANE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150322089A1

  公开（公告）日：2015-11-12

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  本披露提供了公式I的化合物及其盐，以及使用该化合物的组合物和方法。这些化合物是尼古丁α7受体的配体，可用于治疗中枢神经系统的各种疾病，特别是情感和神经退行性疾病。
• US9458179B2
  申请人：——

  公开号：US9458179B2

  公开（公告）日：2016-10-04
• (−)-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.
• Design and Synthesis of a New Series of 4-Heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes as α7 Nicotinic Receptor Agonists. 1. Development of Pharmacophore and Early Structure–Activity Relationship
  作者：James Cook、F. Christopher Zusi、Ivar M. McDonald、Dalton King、Matthew D. Hill、Christiana Iwuagwu、Robert A. Mate、Haiquan Fang、Rulin Zhao、Bei Wang、Jingfang Cutrone、Baoqing Ma、Qi Gao、Ronald J. Knox、Michele Matchett、Lizbeth Gallagher、Meredith Ferrante、Debra Post-Munson、Thaddeus Molski、Amy Easton、Regina Miller、Kelli Jones、Siva Digavalli、Francine Healy、Kimberley Lentz、Yulia Benitex、Wendy Clarke、Joanne Natale、Judith A. Siuciak、Nicholas Lodge、Robert Zaczek、Rex Denton、Daniel Morgan、Linda J. Bristow、John E. Macor、Richard E. Olson

  DOI：10.1021/acs.jmedchem.6b01506

  日期：2016.12.22

  The design and synthesis of a series of quinuclidine-containing spirooxazolidines (“spiroimidates”) and their utility as α7 nicotinic acetylcholine receptor partial agonists are described. Selected members of the series demonstrated excellent selectivity for α7 over the highly homologous 5-HT3A receptor. Modification of the N-spiroimidate heterocycle substituent led to (1S,2R,4S)-N-isoquinolin-3-y

  描述了一系列含喹核苷的螺杂恶唑烷（“螺酰胺化物”）的设计和合成及其作为α7烟碱型乙酰胆碱受体部分激动剂的用途。该系列的选定成员对α7的选择性优于高度同源的5-HT 3A受体。所述的修饰Ñ导致（1 -spiroimidate杂环取代基小号，2 - [R，4小号- ）ñ -异喹啉-3-基）-4' ħ -4-氮杂螺[二环[2.2.2]辛烷-2,5-'恶唑] -2'-胺（BMS-902483），一种有效的α7部分激动剂，可改善临床前啮齿动物模型的认知度。