2-(6-methylamino-3-pyridinyl)-1-benzofuran-5-ol | 1054629-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 2-(6-methylamino-3-pyridinyl)-1-benzofuran-5-ol
• 英文别名: 2-(6-(methylamino)pyridin-3-yl)benzofuran-5-ol；2-(6-Methylamino-pyridin-3-yl)-benzofuran-5-ol；2-[6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol
• CAS: 1054629-36-5
• 化学式: C₁₄H₁₂N₂O₂
• 分子量: 240.261
• InChiKey: YOQRASPYXLBVOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  58.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(6-methylamino-3-pyridinyl)-1-benzofuran-5-ol 在 咪唑 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 tert-butyl 5-(5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-1-benzofuran-2-yl)-2-pyridinyl-N-methylcarbamate
  参考文献：
  名称：

  Novel ¹⁸F-Labeled Benzofuran Derivatives with Improved Properties for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques in Alzheimer’s Brains

  摘要：

  In vivo imaging of beta-amyloid plaques in the brain may lead to the early diagnosis of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. In the present study, we report on the development two potential PET probes, [F-18]FPYBF-2 ([F-18]10) and [F-18]FPHBF-2 ([F-18]21), for imaging of beta-amyloid plagues in AD brain. In experiments in vitro, 10 and 21 displayed high affinity for A beta(1-42) aggregates (K-i = 2.41 and 3.85 nM, respectively). In biodistribution experiments using normal mice, they displayed high uptake in the brain (7.38 and 8.18% ID/g at 2 mm postinjection,, respectively), and the radioactivity washed out from the, brain rapidly (3.15 and 3.87% ID/g at 60 min postinjection, respectively), which is highly desirable for beta-amyloid imaging agents. In vivo, they clearly labeled beta-amyloid plaques in Tg2576 mice. Furthermore, the specific labeling of beta-amyloid plaques by 10 and 21 was observed in autoradiographs of sections of autopsied AD brain. These new fluorinated benzofuran derivatives are promising PET probes for imaging cerebral beta-amyloid plaques.

  DOI：

  10.1021/jm200057u
• 作为产物：
  描述：

  5-甲氧基苯并呋喃-2-硼酸 在 四(三苯基膦)钯 、 sodium methylate 、 三溴化硼 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 2-(6-methylamino-3-pyridinyl)-1-benzofuran-5-ol
  参考文献：
  名称：

  net 99m标记的吡啶基苯并呋喃衍生物作为阿尔茨海默氏症大脑中β淀粉样蛋白斑块的单光子发射计算机断层成像成像探针

  摘要：

  测试了三种新颖的99m Tc标记的吡啶基苯并呋喃衍生物，作为使用单光子发射计算机断层扫描（SPECT）对β-淀粉样蛋白斑进行成像的潜在探针。的99米Tc和对应铼复合物用双（氨基乙硫醇）（BAT）作为螯合配体合成。所有Re复合物均显示出对Aβ（1-42）聚集体的亲和力（K i = 13.6-149.6 nM）。在正常小鼠中进行的生物分布实验表明，99m Tc标记的衍生物在大脑中显示出足够的摄取（注射后2分钟为1.41–1.80％ID / g）。值得注意的是，[ 99mTc] BAT-Bp-2表现出良好的初始摄取（2分钟时为1.80％ID / g）和合理的脑液冲洗（60分钟时为0.79％ID / g）。用[ 99m Tc] BAT-Bp-2进行的放射自显影显示，在Tg2576转基因小鼠的脑组织切片中，β-淀粉样斑块有大量标记，而在年龄匹配的对照中则没有。[ 99m Tc] BAT-Bp-2可能

  DOI：

  10.1021/jm201513c

文献信息

• [EN] NITROXIDE CONTAINING AMYLOID BINDING AGENTS FOR IMAGING AND THERAPEUTIC USES<br/>[FR] AGENTS DE LIAISON À L'AMYLOÏDE CONTENANT DU NITROXYDE UTILISÉS EN IMAGERIE ET À DES FINS THÉRAPEUTIQUES
  申请人：UNIV CALIFORNIA

  公开号：WO2017031239A1

  公开（公告）日：2017-02-23

  The present invention provides methods of using nitroxide spin-labeled amyloid beta-binding compounds to image amyloid. The present invention also provides nitroxide spin-labeled amyloid beta-binding compounds

  本发明提供了使用亚硝基自旋标记的淀粉样β结合化合物来成像淀粉样物质的方法。本发明还提供了亚硝基自旋标记的淀粉样β结合化合物。
• Novel 2-Heteroaryl Substituted Benzothiophenes and Benzofuranes 709
  申请人：Arzel Erwan

  公开号：US20080221149A1

  公开（公告）日：2008-09-11

  The present invention relates to novel 2-heteroaryl substituted benzothiophene and benzofuran derivatives, precursors thereof, and therapeutic uses of such compounds, having the structural formula (Ia) below: and to their pharmaceutically acceptable salt, compositions and methods of use. Furthermore, the invention relates to novel 2-heteroaryl substituted benzothiophene and benzofuran derivatives that are suitable for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. More specifically, the present invention relates to a method of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease as well as measureing clinical efficacy of Alzheimer's disease therapeutic agents.

  本发明涉及新型2-杂环芳基取代苯并噻吩和苯并呋喃衍生物，其前体以及这些化合物的治疗用途，具有如下结构式(Ia)： 以及它们的药用盐、组合物和使用方法。此外，本发明涉及适用于在活体患者中成像淀粉样沉积物的新型2-杂环芳基取代苯并噻吩和苯并呋喃衍生物，它们的组合物、使用方法以及制备这类化合物的过程。更具体地，本发明涉及一种在体内成像脑部淀粉样沉积物的方法，以允许在死前诊断阿尔茨海默病，并测量阿尔茨海默病治疗药物的临床疗效。
• (R)- and (S)-18F-labeled 2-arylbenzofurans with improved pharmacokinetics as β-amyloid imaging probes
  作者：Jia Song、Xiaoyang Zhang、Yunling Zhao、Hui Yang、Jinming Zhang、Xiaojun Zhang、Jiapei Dai、Mengchao Cui

  DOI：10.1016/j.ejmech.2017.03.073

  日期：2017.7

  mouse and AD human brain tissue after labeled by 18F. The purified enantiomers displayed apparent discrepancy in biodistribution experiments in normal mice, for (S)-enantiomers provided rather faster clearance than (R)-enantiomers. All in all, (S)-[18F]17 (Ki = 14.6 nM) with excellent pharmacokinetics (brain2 min = 8.60% ID/g, brain2 min/brain60 min = 14.1) deserves further evaluation.

  合成了一类新型的2-芳基苯并呋喃衍生物的光学异构体，并将其评估为潜在的β-淀粉样蛋白斑成像剂。亲脂性和信噪比都大大改善了手性羟基添加到1-氟-3-（氧代烷基）丙烷-2-醇侧链。这些衍生物显示出对Aβ1-42聚集体的中等至高结合亲和力。选择了四个具有强结合亲和力（Ki <30 nM）的示踪剂用于进一步研究。在体外放射自显影研究中，四种探针在18F标记后显示出与Tg小鼠和AD人脑组织中Aβ斑块的有效结合。纯化的对映异构体在正常小鼠的生物分布实验中显示出明显的差异，因为（S）-对映异构体提供的清除速度比（R）-对映异构体快。总计，（S）-[18F] 17（Ki = 14。
• 2-heteroaryl substituted benzothiophenes and benzofuranes 709
  申请人：Astrazeneca AB

  公开号：US07772256B2

  公开（公告）日：2010-08-10

  The present invention relates to novel 2-heteroaryl substituted benzothiophene and benzofuran derivatives, precursors thereof, and therapeutic uses of such compounds, having the structural formula (Ia) below: and to their pharmaceutically acceptable salt, compositions and methods of use. Furthermore, the invention relates to novel 2-heteroaryl substituted benzothiophene and benzofuran derivatives that are suitable for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. More specifically, the present invention relates to a method of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease as well as measuring clinical efficacy of Alzheimer's disease therapeutic agents.

  本发明涉及新型的2-杂环芳基取代苯并噻吩和苯并呋喃衍生物、其前体以及这些化合物的治疗用途，其结构式（Ia）如下： 并且本发明涉及适用于成像活体患者中淀粉样沉积物的新型2-杂环芳基取代苯并噻吩和苯并呋喃衍生物、其组成、使用方法以及制备这些化合物的过程。更具体地，本发明涉及一种在体内成像脑中淀粉样沉积物的方法，以允许抗死前诊断阿尔茨海默病以及测量阿尔茨海默病治疗剂的临床疗效。此外，本发明还涉及这些化合物的药学可接受的盐、组成物和使用方法。
• Nitroxide containing amyloid binding agents for imaging and therapeutic uses
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10478513B2

  公开（公告）日：2019-11-19

  The present invention provides methods of using nitroxide spin-labeled amyloid beta-binding compounds to image amyloid. The present invention also provides nitroxide spin-labeled amyloid beta-binding compounds.

  本发明提供了使用亚硝基自旋标记的淀粉样蛋白 beta 结合化合物对淀粉样蛋白成像的方法。本发明还提供了亚硝基自旋标记的淀粉样 beta 结合化合物。