3-acetonylidene-1-azabicyclo[2.2.2]octane | 189243-26-3

• 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-acetonylidene-1-azabicyclo[2.2.2]octane
• 英文别名: 1-(1-Azabicyclo[2.2.2]octan-3-ylidene)propan-2-one
• CAS: 189243-26-3
• 化学式: C₁₀H₁₅NO
• 分子量: 165.235
• InChiKey: XVFBZAKFUWQJMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-acetonylidene-1-azabicyclo[2.2.2]octane 在 盐酸羟胺 、 溶剂黄146 作用下， 反应 1.0h， 生成 3-(5-isoxazolyl)methylene-1-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  Improving the Nicotinic Pharmacophore with a Series of (Isoxazole)methylene-1-azacyclic Compounds:  Synthesis, Structure−Activity Relationship, and Molecular Modeling

  摘要：

  A series of (isoxazole)methylene-1-azacyclic compounds was prepared. The compounds were tested for affinity to central nicotinic acetylcholine receptors (nAChRs) and central muscarinic receptors. The compounds covered a broad range of affinities for the nAChRs (IC50 = 0.32 to >1000 nM), with selectivities for the nAChRs over the muscarinic receptors in the range of 3-183. The high-affinity compound (Z)-26 (3-(4-methyl-5-isoxazolyl)methylene-1-azabicyclo-[2.2.2]octane, IC50 = 3.2 nM) having only one energy minimum was used as the reference structure in a computational study. This ligand has enabled definition of an important distance parameter, and the existence of this parameter was supported by showing that other potent nicotinic ligands (for example, nicotine and epibatidine) fit the model.

  DOI：

  10.1021/jm9910627
• 作为产物：
  描述：

  3-奎宁环酮 、 丙酮基膦酸二甲酯 在 氢氧化钾 作用下， 以 水 为溶剂， 反应 90.0h， 生成 3-acetonylidene-1-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  Improving the Nicotinic Pharmacophore with a Series of (Isoxazole)methylene-1-azacyclic Compounds:  Synthesis, Structure−Activity Relationship, and Molecular Modeling

  摘要：

  A series of (isoxazole)methylene-1-azacyclic compounds was prepared. The compounds were tested for affinity to central nicotinic acetylcholine receptors (nAChRs) and central muscarinic receptors. The compounds covered a broad range of affinities for the nAChRs (IC50 = 0.32 to >1000 nM), with selectivities for the nAChRs over the muscarinic receptors in the range of 3-183. The high-affinity compound (Z)-26 (3-(4-methyl-5-isoxazolyl)methylene-1-azabicyclo-[2.2.2]octane, IC50 = 3.2 nM) having only one energy minimum was used as the reference structure in a computational study. This ligand has enabled definition of an important distance parameter, and the existence of this parameter was supported by showing that other potent nicotinic ligands (for example, nicotine and epibatidine) fit the model.

  DOI：

  10.1021/jm9910627

文献信息

• NOVEL SUBSTITUTED AZACYCLIC OR AZABICYCLIC COMPOUNDS
  申请人：NOVO NORDISK A/S

  公开号：EP0871627A1

  公开（公告）日：1998-10-21
• [EN] NOVEL SUBSTITUTED AZACYCLIC OR AZABICYCLIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES AZACYCLIQUES OU AZABICYCLIQUES A SUBSTITUTION
  申请人：NOVO NORDISK A/S

  公开号：WO1997011073A1

  公开（公告）日：1997-03-27

  (EN) The present invention relates to therapeutically active heterocyclic compounds, to methods for their preparation and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating diseases in the central nervous system related to malfunctioning of the nicotinic cholinergic system.(FR) Cette invention a trait à des composés hétérocycliques à activité thérapeutique, à des procédés permettant leur préparation ainsi qu'à des compositions pharmaceutiques les contenant. Ces nouveaux composés se révèlent utiles dans le traitement de maladies du système nerveux central liées à un dysfonctionnement du système cholinergique nicotinique.
• Improving the Nicotinic Pharmacophore with a Series of (Isoxazole)methylene-1-azacyclic Compounds:  Synthesis, Structure−Activity Relationship, and Molecular Modeling
  作者：Janne E. Tønder、John Bondo Hansen、Mikael Begtrup、Ingrid Pettersson、Karin Rimvall、Birgitte Christensen、Ulrich Ehrbar、Preben H. Olesen

  DOI：10.1021/jm9910627

  日期：1999.12.2

  A series of (isoxazole)methylene-1-azacyclic compounds was prepared. The compounds were tested for affinity to central nicotinic acetylcholine receptors (nAChRs) and central muscarinic receptors. The compounds covered a broad range of affinities for the nAChRs (IC50 = 0.32 to >1000 nM), with selectivities for the nAChRs over the muscarinic receptors in the range of 3-183. The high-affinity compound (Z)-26 (3-(4-methyl-5-isoxazolyl)methylene-1-azabicyclo-[2.2.2]octane, IC50 = 3.2 nM) having only one energy minimum was used as the reference structure in a computational study. This ligand has enabled definition of an important distance parameter, and the existence of this parameter was supported by showing that other potent nicotinic ligands (for example, nicotine and epibatidine) fit the model.