5,7-dichloro-2-((((1-(3-fluoropropyl)-1H-1,2,3-triazol-4-yl)methyl)(methyl)amino)methyl)quinolin-8-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5,7-dichloro-2-((((1-(3-fluoropropyl)-1H-1,2,3-triazol-4-yl)methyl)(methyl)amino)methyl)quinolin-8-ol
• 英文别名: 5,7-Dichloro-2-[[[1-(3-fluoropropyl)triazol-4-yl]methyl-methylamino]methyl]quinolin-8-ol；5,7-dichloro-2-[[[1-(3-fluoropropyl)triazol-4-yl]methyl-methylamino]methyl]quinolin-8-ol
• 化学式: C₁₇H₁₈Cl₂FN₅O
• 分子量: 398.267
• InChiKey: NUXXSFJGPHANIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  67.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5,7-二氯-8-羟基喹哪啶 在 4-二甲氨基吡啶 、 selenium(IV) oxide 、 sodium tetrahydroborate 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 5,7-dichloro-2-((((1-(3-fluoropropyl)-1H-1,2,3-triazol-4-yl)methyl)(methyl)amino)methyl)quinolin-8-ol
  参考文献：
  名称：

  Novel Fluorinated 8-Hydroxyquinoline Based Metal Ionophores for Exploring the Metal Hypothesis of Alzheimer’s Disease

  摘要：

  Zinc, copper, and iron ions are involved in amyloid-beta (A beta) deposition and stabilization in Alzheimer's disease (AD). Consequently, metal binding agents that prevent metal-A beta interaction and lead to the dissolution of A beta deposits have become well sought therapeutic and diagnostic targets. However, direct intervention between diseases and metal abnormalities has been challenging and is partially attributed to the lack of a suitable agent to determine and modify metal concentration and distribution in vivo. In the search of metal ionophores, we have identified several promising chemical entities by strategic fluorination of 8-hydroxyquinoline drugs, clioquinol, and PBT2. Compounds 15-17 and 28-30 showed exceptional metal ionophore ability (6-40-fold increase of copper uptake and >2-fold increase of zinc uptake) and inhibition of zinc induced A beta oligomerization (EC(50)s < similar to 5 mu M). These compounds are suitable for further development as drug candidates and/or positron emission tomography (PET) biomarkers if radiolabeled with F-18.

  DOI：

  10.1021/acsmedchemlett.5b00281

文献信息

• [EN] 8-HYDROXYQUINOLINE DERIVATIVES AS DIAGNOSTIC AND THERAPEUTIC AGENTS<br/>[FR] DÉRIVÉS DE 8-HYDROXYQUINOLÉINE EN TANT QU'AGENTS DIAGNOSTIQUES ET THÉRAPEUTIQUES
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2017027064A1

  公开（公告）日：2017-02-16

  The present application provides compounds useful in methods of treating neurological disorders such as Alzheimer's disease, and cancer such as prostate cancer. Also provided herein are radiolabeled compounds useful for imaging techniques, and techniques for diagnosis and monitoring of treatment of neurological disorders and cancer. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography or single- photon emission computed tomography. Methods for preparing radiolabeled compounds and methods for preparing unlabeled compounds are also provided.

  本申请提供了在治疗神经系统疾病如阿尔茨海默病以及癌症如前列腺癌方面有用的化合物。本文还提供了用于成像技术的放射标记化合物，以及用于诊断和监测神经系统疾病和癌症治疗的技术。本文提供的示例放射标记化合物可用作正电子发射断层扫描或单光子发射计算机断层扫描的放射追踪剂。还提供了制备放射标记化合物和非标记化合物的方法。
• 8-hydroxyquinoline derivatives as diagnostic and therapeutic agents
  申请人：The General Hospital Corporation

  公开号：US10781178B2

  公开（公告）日：2020-09-22

  The present application provides compounds useful in methods of treating neurological disorders such as Alzheimer's disease, and cancer such as prostate cancer. Also provided herein are radiolabeled compounds useful for imaging techniques, and techniques for diagnosis and monitoring of treatment of neurological disorders and cancer. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography or single-photon emission computed tomography. Methods for preparing radiolabeled compounds and methods for preparing unlabeled compounds are also provided.

  本申请提供了用于治疗神经系统疾病（如阿尔茨海默病）和癌症（如前列腺癌）的化合物。本申请还提供了用于成像技术的放射性标记化合物，以及用于诊断和监测神经系统疾病和癌症治疗的技术。本文提供的一种示例性放射性标记化合物可用作正电子发射计算机断层扫描或单光子发射计算机断层扫描的放射性示踪剂。还提供了制备放射性标记化合物的方法和制备未标记化合物的方法。
• 8-HYDROXYQUINOLINE DERIVATIVES AS DIAGNOSTIC AND THERAPEUTIC AGENTS
  申请人：The General Hospital Corporation

  公开号：US20180327362A1

  公开（公告）日：2018-11-15

  The present application provides compounds useful in methods of treating neurological disorders such as Alzheimer's disease, and cancer such as prostate cancer. Also provided herein are radiolabeled compounds useful for imaging techniques, and techniques for diagnosis and monitoring of treatment of neurological disorders and cancer. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography or single-photon emission computed tomography. Methods for preparing radiolabeled compounds and methods for preparing unlabeled compounds are also provided.
• Novel Fluorinated 8-Hydroxyquinoline Based Metal Ionophores for Exploring the Metal Hypothesis of Alzheimer’s Disease
  作者：Steven H. Liang、Adam G. Southon、Benjamin H. Fraser、Anwen M. Krause-Heuer、Bo Zhang、Timothy M. Shoup、Rebecca Lewis、Irene Volitakis、Yifeng Han、Ivan Greguric、Ashley I. Bush、Neil Vasdev

  DOI：10.1021/acsmedchemlett.5b00281

  日期：2015.9.10

  Zinc, copper, and iron ions are involved in amyloid-beta (A beta) deposition and stabilization in Alzheimer's disease (AD). Consequently, metal binding agents that prevent metal-A beta interaction and lead to the dissolution of A beta deposits have become well sought therapeutic and diagnostic targets. However, direct intervention between diseases and metal abnormalities has been challenging and is partially attributed to the lack of a suitable agent to determine and modify metal concentration and distribution in vivo. In the search of metal ionophores, we have identified several promising chemical entities by strategic fluorination of 8-hydroxyquinoline drugs, clioquinol, and PBT2. Compounds 15-17 and 28-30 showed exceptional metal ionophore ability (6-40-fold increase of copper uptake and >2-fold increase of zinc uptake) and inhibition of zinc induced A beta oligomerization (EC(50)s < similar to 5 mu M). These compounds are suitable for further development as drug candidates and/or positron emission tomography (PET) biomarkers if radiolabeled with F-18.