(5R)-3-(5-methylthiophen-2-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: (5R)-3-(5-methylthiophen-2-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one
• 化学式: C₁₄H₁₈N₂O₂S
• 分子量: 278.375
• InChiKey: ONEVIAVLSXKRGP-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴-5-甲基噻吩 、 (S)-螺[1-氮杂双环[2.2.2]辛烷-3,5'-恶唑啉]-2'-酮 在 copper(l) iodide 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (5R)-3-(5-methylthiophen-2-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one
  参考文献：
  名称：

  Discovery of the α7 Nicotinic Acetylcholine Receptor Agonists. (R)-3‘-(5-Chlorothiophen-2-yl)spiro-1-azabicyclo[2.2.2]octane-3,5‘-[1‘,3‘]oxazolidin-2‘-one as a Novel, Potent, Selective, and Orally Bioavailable Ligand

  摘要：

  Recent advances in molecular biology suggest that neuronal nicotinic acetylcholine receptors play important roles in the central nervous system (CNS). Of these receptors, the 0 group has recently attracted interest for its CNS-related actions and is looked to as a potential new class of pharmacological targets for cognition, schizophrenia, sensory gating, and anxiety. In the course of a research program aimed at the discovery of alpha 7 receptor agonists with high affinity, subtype selectivity, and good pharmacokinetic profile, we discovered (R)-3'(5-chlorothiophen-2-yl)spiro-l-azabicyclo[2.2.2]octane-3,5'-[1',3'loxazolidin-2'-one (25). Compound 25 has potent binding affinity (K-i = 9 nmol/L) and good selectivity toward the other nicotinic subtypes (alpha A beta 2 and a1 beta 2 gamma delta) and has been found in pharmacokinetic evaluation to have good oral bioavailability and brain permeability.

  DOI：

  10.1021/jm049188d

文献信息

• Discovery of the α7 Nicotinic Acetylcholine Receptor Agonists. (<i>R</i>)-3‘-(5-Chlorothiophen-2-yl)spiro-1-azabicyclo[2.2.2]octane-3,5‘-[1‘,3‘]oxazolidin-2‘-one as a Novel, Potent, Selective, and Orally Bioavailable Ligand
  作者：Ryo Tatsumi、Masakazu Fujio、Hiroyuki Satoh、Jiro Katayama、Shin-ichi Takanashi、Kenji Hashimoto、Hiroshi Tanaka

  DOI：10.1021/jm049188d

  日期：2005.4.1

  Recent advances in molecular biology suggest that neuronal nicotinic acetylcholine receptors play important roles in the central nervous system (CNS). Of these receptors, the 0 group has recently attracted interest for its CNS-related actions and is looked to as a potential new class of pharmacological targets for cognition, schizophrenia, sensory gating, and anxiety. In the course of a research program aimed at the discovery of alpha 7 receptor agonists with high affinity, subtype selectivity, and good pharmacokinetic profile, we discovered (R)-3'(5-chlorothiophen-2-yl)spiro-l-azabicyclo[2.2.2]octane-3,5'-[1',3'loxazolidin-2'-one (25). Compound 25 has potent binding affinity (K-i = 9 nmol/L) and good selectivity toward the other nicotinic subtypes (alpha A beta 2 and a1 beta 2 gamma delta) and has been found in pharmacokinetic evaluation to have good oral bioavailability and brain permeability.