6-fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine | 1054629-56-9

• 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: 6-fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine
• 英文别名: 6-fluoro-5-(5-methoxy-benzofuran-2-yl)-pyridin-2-ylamine
• CAS: 1054629-56-9
• 化学式: C₁₄H₁₁FN₂O₂
• 分子量: 258.252
• InChiKey: NXKHCMJNTQJOCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 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：
  61.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine 在 三溴化硼 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (3H)AZD4694
  参考文献：
  名称：

  Synthesis and evaluation of pyridylbenzofuran, pyridylbenzothiazole and pyridylbenzoxazole derivatives as 18F-PET imaging agents for β-amyloid plaques

  摘要：

  The synthesis and SAR of new beta-amyloid binding agents are reported. Evaluation of important properties for achieving good signal-to-background ratio is described. Compounds 27, 33, and 36 displayed desirable lipophilic and pharmacokinetic properties. Compound 27 was further evaluated with autoradiographic studies in vitro on human brain tissue and in vivo in Tg2576 mice. Compound 27 showed an increased signal-to-background ratio compared to flutemetamol 4, indicating its suitability as PET ligand for b-amyloid deposits in AD patients. The preparation of the corresponding F-18-labeled PET radioligand of compound 27 is presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.011
• 作为产物：
  描述：

  5-甲氧基苯并呋喃-2-硼酸 、 5-溴-6-氟吡啶-2-胺 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 作用下， 以 乙醇 为溶剂， 生成 6-fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine
  参考文献：
  名称：

  [EN] NOVEL DEUTERIUM SUBSTITUTED POSITRON EMISSION TOMOGRAPHY (PET) IMAGING AGENTS AND THEIR PHARMACOLOGICAL APPLICATION
  [FR] NOUVEAUX AGENTS D'IMAGERIE PAR TOMOGRAPHIE PAR ÉMISSION DE POSITRONS (PET) SUBSTITUÉS PAR DU DEUTÉRIUM ET LEUR APPLICATION PHARMACOLOGIQUE

  摘要：

  本发明涉及根据式I-A、式II-A、式II-D和式III-A的氘代化合物。这些化合物可用作PET成像剂，用于评估帕金森病、阿尔茨海默病，并确定特定的选择性5-羟色胺再摄取抑制剂（SSRIi）活性，用于治疗抑郁症。本发明还涉及包括药用可接受载体和式I-A、式II-A、式II-D或式III-A的化合物，或其药用可接受盐的药物组合物。

  公开号：

  WO2018222549A1

文献信息

• 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。
• [EN] NOVEL DEUTERIUM SUBSTITUTED POSITRON EMISSION TOMOGRAPHY (PET) IMAGING AGENTS AND THEIR PHARMACOLOGICAL APPLICATION<br/>[FR] NOUVEAUX AGENTS D'IMAGERIE PAR TOMOGRAPHIE PAR ÉMISSION DE POSITRONS (PET) SUBSTITUÉS PAR DU DEUTÉRIUM ET LEUR APPLICATION PHARMACOLOGIQUE
  申请人：FIVE ELEVEN PHARMA INC

  公开号：WO2018222549A1

  公开（公告）日：2018-12-06

  The present invention relates to deuterated compounds according to Formula I-A, Formula II-A, Formula II-D, and Formula III-A. These compounds can be used as PET imaging agents for evaluating Parkinson's Disease, Alzheimer Disease, and for determining specific serotonin reuptake inhibitor (SSRIi) activity for treatment of depression. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I-A, Formulae II-A, Formula II-D, or Formula III-A, or a pharmaceutically acceptable salt thereof.

  本发明涉及根据式I-A、式II-A、式II-D和式III-A的氘代化合物。这些化合物可用作PET成像剂，用于评估帕金森病、阿尔茨海默病，并确定特定的选择性5-羟色胺再摄取抑制剂（SSRIi）活性，用于治疗抑郁症。本发明还涉及包括药用可接受载体和式I-A、式II-A、式II-D或式III-A的化合物，或其药用可接受盐的药物组合物。
• 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。
• Deuterium substituted positron emission tomography (PET) imaging agents and their pharmacological application
  申请人：Five Eleven Pharma Inc.

  公开号：US10912849B2

  公开（公告）日：2021-02-09

  The present invention relates to deuterated compounds according to Formula I-A, Formula II-A, Formula II-D, and Formula III-A. These compounds can be used as PET imaging agents for evaluating Parkinson's Disease, Alzheimer Disease, and for determining specific serotonin reuptake inhibitor (SSRIi) activity for treatment of depression. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I-A, Formulae II-A, Formula II-D, or Formula III-A, or a pharmaceutically acceptable salt thereof.

  本发明涉及符合式 I-A、式 II-A、式 II-D 和式 III-A 的氚代化合物。这些化合物可用作 PET 成像剂，用于评估帕金森病、阿尔茨海默病，以及确定治疗抑郁症的特异性血清素再摄取抑制剂 (SSRIi) 的活性。本发明还涉及药物组合物，其包含药物可接受载体和式 I-A、式 II-A、式 II-D 或式 III-A 的化合物或其药物可接受盐。
• Characterization of AZD4694, a novel fluorinated Aβ plaque neuroimaging PET radioligand
  作者：Anders Juréus、Britt-Marie Swahn、Johan Sandell、Fredrik Jeppsson、Allan E. Johnson、Peter Johnström、Jan A. M. Neelissen、Dan Sunnemark、Lars Farde、Samuel P. S. Svensson

  DOI：10.1111/j.1471-4159.2010.06812.x

  日期：——

  J. Neurochem. (2010) 114, 784–794.AbstractPositron emission tomography (PET) radioligands that bind selectively to β‐amyloid plaques (Aβ) are promising imaging tools aimed at supporting the diagnosis of Alzheimer’s disease and the evaluation of new drugs aiming to modify amyloid plaque load. For extended clinical use, there is a particular need for PET tracers labeled with fluorine‐18, a radionuclide with 110 min half‐life allowing for central synthesis followed by wide distribution. The development of fluorinated radioligands is, however, challenging because of the lipophilic nature of aromatic fluorine, rendering fluorinated ligands more prone to have high non‐specific white matter binding. We have here developed the new benzofuran‐derived radioligand containing fluorine, AZD4694 that shows high affinity for β‐amyloid fibrils in vitro (Kd = 2.3 ± 0.3 nM). In cortical sections from human Alzheimer’s disease brain [3H]AZD4694 selectively labeled β‐amyloid deposits in gray matter, whereas there was a lower level of non‐displaceable binding in plaque devoid white matter. Administration of unlabeled AZD4694 to rat showed that it has a pharmacokinetic profile consistent with good PET radioligands, i.e., it quickly entered and rapidly cleared from normal rat brain tissue. Ex vivo binding data in aged Tg2576 mice after intravenous administration of [3H]AZD4694 showed selective binding to β‐amyloid deposits in a reversible manner. In Tg2576 mice, plaque bound [3H]AZD4694 could still be detected 80 min after i.v. administration. Taken together, the preclinical profile of AZD4694 suggests that fluorine‐18 labeled AZD4694 may have potential for PET‐visualization of cerebral β‐amyloid deposits in the living human brain.