(R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin]-2'-one | 360043-74-9

• 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: (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin]-2'-one
• 英文别名: (5R)-3-(5-bromothiophen-2-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one
• CAS: 360043-74-9
• 化学式: C₁₃H₁₅BrN₂O₂S
• 分子量: 343.244
• InChiKey: IOQWLUAQJKWRCD-CYBMUJFWSA-N

物化性质

• 熔点：
  180-182 °C(Solv: ethanol (64-17-5))
• 沸点：
  442.5±45.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin]-2'-one 、 三正丁基2-吡啶基锌 在 四(三苯基膦)钯 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以to give the title compound as a pale solid (73 mg), m/z 342 (MH+)的产率得到(R)-3'-[5-(2-pyridinyl)thiophen-2-yl]spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin]-2'-one
  参考文献：
  名称：

  Spiro '1-azabicyclo' 2.2.2! octan-3,5'-oxazolidin - 2'-one! derivatives with affinity to the alpha7 nicotinic acetylcholine receptor

  摘要：

  公式I的化合物及其药用可接受盐，其中Q、Ar1、A和Ar2的定义如规范中所述，包含它们的药物组合物和制剂，使用它们单独或与其他治疗活性化合物或物质联合治疗疾病和症状的方法，用于制备它们的过程和中间体，将它们用于治疗的药物用途，将它们用于制造药物的用途以及将它们用于诊断和分析目的的用途。

  公开号：

  US20060154945A1
• 作为产物：
  描述：

  (R)-3'-(thiophen-2-yl)spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin]-2'-one 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 3.0h， 生成 (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin]-2'-one
  参考文献：
  名称：

  [EN] SPIRO '1-AZABICYCLO '2.2.2!OCTAN-3,5'-OXAZOLIDIN -2'-ONE! DERIVATIVES WITH AFFINITY TO THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR
  [FR] DERIVES DE SPIRO '1-AZABICYCLO '2.2.2!OCTAN-3,5'-OXAZOLIDIN -2'-ONE! POSSEDANT UNE AFFINITE AVEC LE RECEPTEUR D'ACETYLCHOLINE NICOTINIQUE ALPHA7

  摘要：

  式(I)的化合物及其药用盐，其中Arl、A和Ar2如规范中所定义，含有它们的药用组合物和配方，使用它们单独或与其他治疗活性化合物或物质结合治疗疾病和状况的方法，用于制备它们的过程和中间体，用作治疗药物的用途，用于制造药物的用途以及用于诊断和分析目的的用途。

  公开号：

  WO2005005435A1

文献信息

• [EN] SPIRO '1-AZABICYCLO '2.2.2!OCTAN-3,5'-OXAZOLIDIN -2'-ONE! DERIVATIVES WITH AFFINITY TO THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR<br/>[FR] DERIVES DE SPIRO '1-AZABICYCLO '2.2.2!OCTAN-3,5'-OXAZOLIDIN -2'-ONE! POSSEDANT UNE AFFINITE AVEC LE RECEPTEUR D'ACETYLCHOLINE NICOTINIQUE ALPHA7
  申请人：ASTRAZENECA AB

  公开号：WO2005005435A1

  公开（公告）日：2005-01-20

  Compounds of formula (I) and pharmaceutically-acceptable salts thereof, wherein Arl, A and Ar2 are as defined in the specification, pharmaceutical compositions and formulations containing them, methods of using them to treat diseases and conditions either alone or in combination with other therapeutically-active compounds or substances, processes and intermediates used to prepare them, uses of them as medicaments for therapy, uses of them in the manufacture of medicaments and uses of them for diagnostic and analytic purposes.

  式(I)的化合物及其药用盐，其中Arl、A和Ar2如规范中所定义，含有它们的药用组合物和配方，使用它们单独或与其他治疗活性化合物或物质结合治疗疾病和状况的方法，用于制备它们的过程和中间体，用作治疗药物的用途，用于制造药物的用途以及用于诊断和分析目的的用途。
• Oxazolidinone nicotinic acetylcholine receptor agonists
  申请人：AstraZeneca AB

  公开号：US07514567B2

  公开（公告）日：2009-04-07

  Compounds of formula I: and pharmaceutically-acceptable salts thereof, wherein Q, Ar1, A and Ar2 are as defined in the specification, pharmaceutical compositions and formulations containing them, methods of using them to treat diseases and conditions either alone or in combination with other therapeutically-active compounds or substances, processes and intermediates used to prepare them, uses of them as medicaments for therapy, uses of them in the manufacture of medicaments and uses of them for diagnostic and analytic purposes.

  公式I的化合物及其药用可接受盐，其中Q、Ar1、A和Ar2如规范所定义，含有它们的药用组合物和配方，使用它们治疗疾病和病况的方法，可以单独使用或与其他治疗活性化合物或物质结合使用，用于制备它们的过程和中间体，将它们用作治疗药物的用途，将它们用于制造药物的用途以及将它们用于诊断和分析目的的用途。
• SPIRO [1-AZABICYCLO [2.2.2]OCTANE-3,5'-OXAZOLIDIN-2'-ONE] DERIVATIVES WITH AFFINITY TO THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR
  申请人：AstraZeneca AB

  公开号：EP1654264A1

  公开（公告）日：2006-05-10
• US7514567B2
  申请人：——

  公开号：US7514567B2

  公开（公告）日：2009-04-07
• 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.