3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-fluorodibenzo[b,d]thiophene 5,5-dioxide | 1456878-22-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-fluorodibenzo[b,d]thiophene 5,5-dioxide
• 英文别名: 4-(6-Fluoro-5,5-dioxido-3-dibenzothienyl)-1,4-diazabicyclo(3.2.2)nonane；3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-fluorodibenzothiophene 5,5-dioxide
• CAS: 1456878-22-0
• 化学式: C₁₉H₁₉FN₂O₂S
• 分子量: 358.436
• InChiKey: JIGWWGDIEUWCOR-UHFFFAOYSA-N

物化性质

• 沸点：
  578.7±45.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  49
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-fluorodibenzo[b,d]thiophene 5,5-dioxide 、 对甲苯磺酸 以 乙醇 、 乙酸乙酯 为溶剂， 反应 2.0h， 以72%的产率得到3-(1,4-Diazabicyclo[3.2.2]nonan-4-yl)-6-fluorodibenzothiophene 5,5-dioxide;4-methylbenzenesulfonic acid
  参考文献：
  名称：

  DERIVATIVES OF DIBENZOTHIOPHENE IMAGING OF alpha-7 NICOTINIC ACETYLCHOLINE RECEPTORS

  摘要：

  目前披露的主题提供了非侵入性的成像方法，量化α7烟碱性胆碱受体，并诊断与α7-nAChRs相关的疾病或病况。还提供了制备二苯并噻吩的放射性标记衍生物和所提供化合物的方法。

  公开号：

  US20160235869A1
• 作为产物：
  描述：

  2-氟苯硫酚 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 双氧水 、 铁粉 、 氯化铵 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 57.0h， 生成 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-fluorodibenzo[b,d]thiophene 5,5-dioxide
  参考文献：
  名称：

  Derivatives of Dibenzothiophene for Positron Emission Tomography Imaging of α7-Nicotinic Acetylcholine Receptors

  摘要：

  A new series of derivatives of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)dibenzo[b,d]thiophene 5,5-dioxide with high binding affinities and selectivity for alpha 7-nicotinic acetylcholine receptors (alpha 7-nAChRs) (K-i = 0.4-20 nM) has been synthesized for positron emission tomography (PET) imaging of alpha 7-nAChRs. Two radiolabeled members of the series [F-18]7a (K-i = 0.4 nM) and [F-18]7c (K-i = 1.3 nM) were synthesized. [F-18]7a and [F-18]7c readily entered the mouse brain and specifically labeled alpha 7-nAChRs. The alpha 7-nAChR selective ligand 1 (SSR180711) blocked the binding of [F-18]7a in the mouse brain in a dose-dependent manner. The mouse blocking studies with non-alpha 7-nAChR central nervous system drugs demonstrated that [F-18]7a is highly alpha 7-nAChR selective. In agreement with its binding affinity the binding potential of [F-18]7a (BPND = 5.3-8.0) in control mice is superior to previous alpha 7-nAChR PET radioligands. Thus, [F-18]7a displays excellent imaging properties in mice and has been chosen for further evaluation as a potential PET radioligand for imaging of alpha 7-nAChR in non-human primates.

  DOI：

  10.1021/jm401184f

文献信息

• A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand
  作者：Rodrigo Teodoro、Matthias Scheunemann、Winnie Deuther-Conrad、Barbara Wenzel、Francesca Fasoli、Cecilia Gotti、Mathias Kranz、Cornelius Donat、Marianne Patt、Ansel Hillmer、Ming-Qiang Zheng、Dan Peters、Jörg Steinbach、Osama Sabri、Yiyun Huang、Peter Brust

  DOI：10.3390/molecules201018387

  日期：——

  Changes in the expression of α₇ nicotinic acetylcholine receptors (α₇ nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET). We report on a series of new ligands for α₇ nAChRs

  人们普遍认为，人脑中α₇烟碱型乙酰胆碱受体（α₇nAChRs）表达的变化与神经和神经肿瘤学过程有关。在体内对这些受体的研究取决于成像剂的可用性，例如可用于正电子发射断层扫描（PET）的放射性标记的配体。我们报告了一系列有关α₇nAChR的新配体，这些配体是由二苯并噻吩二氧化物作为一种新颖的氢键受体官能团与二氮杂双环壬烷作为已建立的阳离子中心而设计的。为了评估这种新的基本结构的构效关系（SAR），我们通过引入三种不同的基于哌嗪的支架进一步系统地修饰了阳离子中心。根据体外结合亲和力和选择性，通过在不同的大鼠和人类nAChR亚型以及与结构相关的人类5-HT₃受体进行的放射性配体置换研究评估，我们选择了化合物7-（1,4-二氮杂双环[3.2.2] nonan-4-yl）-2-氟二苯并-[b，d]噻吩5,5-二氧化物（10a）用于放射性标记和体内进一步评估。优化了[18F] 10a的放射合成，并将其
• Modified ligand-gated ion channels and methods of use
  申请人：Howard Hughes Medical Institute

  公开号：US10981962B2

  公开（公告）日：2021-04-20

  This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.

  本文涉及控制配体门控离子通道（LGIC）活性的材料和方法。例如，提供了包括至少一个具有修饰配体结合结构域（LBD）和/或修饰离子孔结构域（IPD）的 LGIC 亚基的修饰 LGIC。此外，还提供了可与经修饰的 LGIC 结合并激活该 LGIC 的外源 LGIC 配体，以及调节哺乳动物细胞膜上离子转运的方法、调节哺乳动物细胞兴奋性的方法和治疗患有通道病的哺乳动物的方法。
• MODIFIED LIGAND-GATED ION CHANNELS AND METHODS OF USE
  申请人：Howard Hughes Medical Institute

  公开号：US20210206831A1

  公开（公告）日：2021-07-08

  This document relates to materials and methods for modulating ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.