3-(3-bromophenyl)-5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-bromophenyl)-5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole
• 英文别名: 5-(1-Azabicyclo[2.2.2]octan-3-ylmethyl)-3-(3-bromophenyl)-1,2,4-oxadiazole；5-(1-azabicyclo[2.2.2]octan-3-ylmethyl)-3-(3-bromophenyl)-1,2,4-oxadiazole
• 化学式: C₁₆H₁₈BrN₃O
• 分子量: 348.242
• InChiKey: UFWLIVJXSVSVNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-bromophenyl)-5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole 、 富马酸 以 甲醇 为溶剂， 反应 2.0h， 以55%的产率得到3-(3-bromophenyl)-5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole fumarate
  参考文献：
  名称：

  Novel 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazoles to investigate the activation of the α7 nicotinic acetylcholine receptor subtype: Synthesis and electrophysiological evaluation

  摘要：

  alpha 7 nicotinic acetylcholine receptors (nAChRs) are relevant therapeutic targets for a variety of disorders alpha including neurodegeneration, cognitive impairment, and inflammation. Although traditionally identified as an ionotropic receptor, the alpha 7 subtype showed metabotropic-like functions, mainly linked to the modulation of immune responses. In the present work, we investigated the structure-activity relationships in a set of novel alpha 7 ligands incorporating the 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole scaffold, i.e. derivatives 21a-34a and 21b-34b, aiming to identify the structural requirements able to preferentially trigger one of the two activation modes of this receptor subtype. The new compounds were characterized as partial and silent alpha 7 nAChR agonists in electrophysiological assays, which allowed to assess the contribution of the different groups towards the final pharmacological profile. Overall, modifications of the selected structural backbone mainly afforded partial agonists, among them tertiary bases 27a-33a, whereas additional hydrogen -bond acceptor groups in permanently charged ligands, such as 29b and 31b, favored a silent desensitizing profile at the alpha 7 nAChR. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.10.015
• 作为产物：
  描述：

  methyl 2-(quinuclidin-3-yl)acetate 在 caesium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 13.83h， 生成 3-(3-bromophenyl)-5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Novel 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazoles to investigate the activation of the α7 nicotinic acetylcholine receptor subtype: Synthesis and electrophysiological evaluation

  摘要：

  alpha 7 nicotinic acetylcholine receptors (nAChRs) are relevant therapeutic targets for a variety of disorders alpha including neurodegeneration, cognitive impairment, and inflammation. Although traditionally identified as an ionotropic receptor, the alpha 7 subtype showed metabotropic-like functions, mainly linked to the modulation of immune responses. In the present work, we investigated the structure-activity relationships in a set of novel alpha 7 ligands incorporating the 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole scaffold, i.e. derivatives 21a-34a and 21b-34b, aiming to identify the structural requirements able to preferentially trigger one of the two activation modes of this receptor subtype. The new compounds were characterized as partial and silent alpha 7 nAChR agonists in electrophysiological assays, which allowed to assess the contribution of the different groups towards the final pharmacological profile. Overall, modifications of the selected structural backbone mainly afforded partial agonists, among them tertiary bases 27a-33a, whereas additional hydrogen -bond acceptor groups in permanently charged ligands, such as 29b and 31b, favored a silent desensitizing profile at the alpha 7 nAChR. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.10.015

文献信息

• Novel 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazoles to investigate the activation of the α7 nicotinic acetylcholine receptor subtype: Synthesis and electrophysiological evaluation
  作者：Marta Quadri、Almin Silnović、Carlo Matera、Nicole A. Horenstein、Clare Stokes、Marco De Amici、Roger L. Papke、Clelia Dallanoce

  DOI：10.1016/j.ejmech.2018.10.015

  日期：2018.12

  alpha 7 nicotinic acetylcholine receptors (nAChRs) are relevant therapeutic targets for a variety of disorders alpha including neurodegeneration, cognitive impairment, and inflammation. Although traditionally identified as an ionotropic receptor, the alpha 7 subtype showed metabotropic-like functions, mainly linked to the modulation of immune responses. In the present work, we investigated the structure-activity relationships in a set of novel alpha 7 ligands incorporating the 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole scaffold, i.e. derivatives 21a-34a and 21b-34b, aiming to identify the structural requirements able to preferentially trigger one of the two activation modes of this receptor subtype. The new compounds were characterized as partial and silent alpha 7 nAChR agonists in electrophysiological assays, which allowed to assess the contribution of the different groups towards the final pharmacological profile. Overall, modifications of the selected structural backbone mainly afforded partial agonists, among them tertiary bases 27a-33a, whereas additional hydrogen -bond acceptor groups in permanently charged ligands, such as 29b and 31b, favored a silent desensitizing profile at the alpha 7 nAChR. (C) 2018 Elsevier Masson SAS. All rights reserved.