sodium;(E)-(5-bromopyridin-3-yl)-[1-(diethylaminomethyl)-2-oxopiperidin-3-ylidene]methanolate | 1446750-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: sodium;(E)-(5-bromopyridin-3-yl)-[1-(diethylaminomethyl)-2-oxopiperidin-3-ylidene]methanolate
• CAS: 1446750-50-0
• 化学式: C₁₆H₂₁BrN₃O₂*Na
• 分子量: 390.255
• InChiKey: PZCNQIZKSMOFJA-WPDLWGESSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.16
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴烟酸乙酯 、 N-(N,N-diethylaminomethyl)-2-piperidone 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 7.0h， 生成 sodium 3-(5-bromonicotinoyl)-1-((diethylamino)methyl)-1,4,5,6-tetrahydropyridin-2-olate 、 sodium (Z)-(5-bromopyridin-3-yl)(1-((diethylamino)methyl)-2-oxopiperidin-3-ylidene)methanolate 、 sodium;(E)-(5-bromopyridin-3-yl)-[1-(diethylaminomethyl)-2-oxopiperidin-3-ylidene]methanolate
  参考文献：
  名称：

  Synthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor

  摘要：

  We introduce the term 'silent agonists' to describe ligands that can place the alpha 7 nicotinic acetylcholine receptor (nAChR) into a desensitized state with little or no apparent activation of the ion channel, forming a complex that can subsequently generate currents when treated with an allosteric modulator. KC-1 (5'-phenylanabaseine) was synthesized and identified as a new silent agonist for the alpha 7 nAChR; it binds to the receptor but does not activate alpha 7 nAChR channel opening when applied alone, and its agonism is revealed by co-application with the type II positive allosteric modulator PNU-120596 in the Xenopus oocyte system. The concise synthesis was accomplished in three steps with the C-C bonds formed via Pd-catalyzed mono-arylation and organolithium coupling with N-Boc piperidinone. Comparative structural analyses indicate that a positive charge, an H-bond acceptor, and an aryl ring in a proper arrangement are needed to constitute one class of silent agonist for the alpha 7 nAChR. Because silent agonists may act on signaling pathways not involving ion channel opening, this class of alpha 7 nAChR ligands may constitute a new alternative for the development of alpha 7 nAChR therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.039

文献信息

• Synthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor
  作者：Kinga Chojnacka、Roger L. Papke、Nicole A. Horenstein

  DOI：10.1016/j.bmcl.2013.05.039

  日期：2013.7

  We introduce the term 'silent agonists' to describe ligands that can place the alpha 7 nicotinic acetylcholine receptor (nAChR) into a desensitized state with little or no apparent activation of the ion channel, forming a complex that can subsequently generate currents when treated with an allosteric modulator. KC-1 (5'-phenylanabaseine) was synthesized and identified as a new silent agonist for the alpha 7 nAChR; it binds to the receptor but does not activate alpha 7 nAChR channel opening when applied alone, and its agonism is revealed by co-application with the type II positive allosteric modulator PNU-120596 in the Xenopus oocyte system. The concise synthesis was accomplished in three steps with the C-C bonds formed via Pd-catalyzed mono-arylation and organolithium coupling with N-Boc piperidinone. Comparative structural analyses indicate that a positive charge, an H-bond acceptor, and an aryl ring in a proper arrangement are needed to constitute one class of silent agonist for the alpha 7 nAChR. Because silent agonists may act on signaling pathways not involving ion channel opening, this class of alpha 7 nAChR ligands may constitute a new alternative for the development of alpha 7 nAChR therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.