4-氨基甲酰吡啶-3-羧酸酯 | 178419-46-0

• 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
• 中文名称: 4-氨基甲酰吡啶-3-羧酸酯
• 英文名称: (R)-spiro-1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin-2'-one
• 英文别名: (R)-(+)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidine-2'-one]；(+)-AAR 17779；Spiro[1-azabicyclo[2.2.2]octane-3,5-oxazolidin]-2-one, (3R)-(9CI)；(5R)-spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one
• CAS: 178419-46-0
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: TYAGAVRSOFABFO-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氨基甲酰吡啶-3-羧酸酯 、 2-溴苯并噻吩 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 (5S)-3-(1-benzothiophen-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
• 作为产物：
  描述：

  ((R)-3-Hydroxy-1-aza-bicyclo[2.2.2]oct-3-yl)-acetic acid hydrazide 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 3.0h， 生成 4-氨基甲酰吡啶-3-羧酸酯
  参考文献：
  名称：

  A Chiral Synthesis of (−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘- oxazolidin-2‘-one]:  A Conformationally Restricted Analogue of Acetylcholine That Is a Potent and Selective α7 Nicotinic Receptor Agonist

  摘要：

  A direct, short chiral synthesis of the selective 0 nicotinic receptor agonist (-)-spiro[l-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (AR-R17779) is presented. The key step utilized attack of the dianion of the (R)-HYTRA ester [(R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate] on quinuclidin-3-one, followed by a selective precipitation of the diasteriomeric tertiary alcohol that led to (S)-(-)-AR-R17779 in two additional steps.

  DOI：

  10.1021/jo049404q

文献信息

• A Chiral Synthesis of (−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘- oxazolidin-2‘-one]:  A Conformationally Restricted Analogue of Acetylcholine That Is a Potent and Selective α7 Nicotinic Receptor Agonist
  作者：John E. Macor、George Mullen、Patrick Verhoest、Anthony Sampognaro、Bruce Shepardson、Robert A. Mack

  DOI：10.1021/jo049404q

  日期：2004.9.1

  A direct, short chiral synthesis of the selective 0 nicotinic receptor agonist (-)-spiro[l-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (AR-R17779) is presented. The key step utilized attack of the dianion of the (R)-HYTRA ester [(R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate] on quinuclidin-3-one, followed by a selective precipitation of the diasteriomeric tertiary alcohol that led to (S)-(-)-AR-R17779 in two additional steps.
• 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.