dihydro-spiro[1-aza-bicyclo[2.2.2]octane-3,2'-furan]-5'-one | 58998-12-2

• 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: dihydro-spiro[1-aza-bicyclo[2.2.2]octane-3,2'-furan]-5'-one
• 英文别名: Spiro[1-azabicyclo[2.2.2]octane-3,5''-2H-tetrahydrofuran-2-one]；spiro[1-azabicyclo[2.2.2]octane-3,5'-oxolane]-2'-one
• CAS: 58998-12-2
• 化学式: C₁₀H₁₅NO₂
• 分子量: 181.235
• InChiKey: QRWOYKHLCWIQAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  螺[1-氮杂双环[2.2.2]辛烷-3,2'-环氧乙烷] 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 41.0h， 生成 dihydro-spiro[1-aza-bicyclo[2.2.2]octane-3,2'-furan]-5'-one
  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

• Nouveaux synthons phosphores : bianions d'hydroxy-1 propene-2 YL phosphonamides, carbanions en β d'acides carboxyliques potentiels.
  作者：Georges Sturtz、Bernard Corbel、Jean-Paul Paugam

  DOI：10.1016/s0040-4039(00)71319-0

  日期：1976.1
• TREATMENT OF INFLAMMATION USING ALPHA 7 RECEPTOR-BINDING CHOLINERGIC AGONISTS
  申请人：Tracey Kevin J.

  公开号：US20110166148A1

  公开（公告）日：2011-07-07

  A method of treating a patient suffering from pancreatitis comprising treating said patient with a therapeutically effective amount of a cholinergic agonist selective for an α7 nicotinic receptor in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from a macrophage wherein said condition is acute pancreatitis. The compounds of the present invention include a quaternary analog of cocaine; (1-aza-bicyclo[2.2.2]oct-3-yl)-carbamic acid 1-(2-fluorophenyl)-ethyl ester; a compound of formula (I), a compound of formula (II), a compound of formula (III), a compound of formula (IV), and an oligonucleotide or mimetic capable of attenuating the symptoms of acute pancreatitis wherein the oligonucleotide or mimetic consists essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an α7 cholinergic receptor. The variables of formulae (I), (II), (III) and (IV) are described herein.
• TREATMENT OF INFLAMMATION USING ALPHA 7 RECEPTOR-BINDING AGONISTS
  申请人：THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH

  公开号：US20150359785A1

  公开（公告）日：2015-12-17

  Methods of inhibiting release of a proinflammatory cytokine from a macrophage are provided. The methods comprise treating the macrophage with a cholinergic agonist in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from the macrophage, wherein the cholinergic agonist is selective for an α7 nicotinic receptor. Methods for inhibiting an inflammatory cytokine cascade in a patient are also provided. The methods comprise treating the patient with a cholinergic agonist in an amount sufficient to inhibit the inflammatory cytokine cascade, wherein the cholinergic agonist is selective for an α7 nicotinic receptor. Methods for determining whether a compound is a cholinergic agonist reactive with an α7 nicotinic receptor are also provided. The methods comprise determining whether the compound inhibits release of a proinflammatory cytokine from a mammalian cell. Additionally, methods for determining whether a compound is a cholinergic antagonist reactive with an α7 nicotinic receptor are provided. These methods comprise determining whether the compound reduces the ability of a cholinergic agonist to inhibit the release of a proinflammatory cytokine from a mammalian cell. Oligonucleotides or mimetics capable of inhibiting attenuation of lipopolysaccharide-induced TNF release from a mammalian macrophage upon exposure of the macrophage to a cholinergic agonist are also provided. The oligonucleotides or mimetics consist essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an α7 receptor. Additionally, methods of inhibiting attenuation of TNF release from a mammalian macrophage upon exposure of the macrophage to a cholinergic agonist are provided. These methods comprise treating the macrophage with the above-described oligonucleotide or mimetic.
• US7238715B2
  申请人：——

  公开号：US7238715B2

  公开（公告）日：2007-07-03
• US7273872B2
  申请人：——

  公开号：US7273872B2

  公开（公告）日：2007-09-25