5,7-dichloro-2-((methylamino)-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-((methylamino)-methyl)quinolin-8-ol
• 英文别名: 5,7-Dichloro-2-(methylaminomethyl)quinolin-8-ol
• 化学式: C₁₁H₁₀Cl₂N₂O
• 分子量: 257.119
• InChiKey: OPSGMYWTPXPZOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,7-dichloro-2-((methylamino)-methyl)quinolin-8-ol 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 5,7-dichloro-2-((((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)(methyl)amino)methyl)quinolin-8-ol
  参考文献：
  名称：

  [EN] 8-HYDROXYQUINOLINE DERIVATIVES AS DIAGNOSTIC AND THERAPEUTIC AGENTS
  [FR] DÉRIVÉS DE 8-HYDROXYQUINOLÉINE EN TANT QU'AGENTS DIAGNOSTIQUES ET THÉRAPEUTIQUES

  摘要：

  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。

  公开号：

  WO2017027064A1
• 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 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 38.0h， 生成 5,7-dichloro-2-((methylamino)-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。
• Metal Protein-Attenuating Compound for PET Neuroimaging: Synthesis and Preclinical Evaluation of [¹¹C]PBT2
  作者：Hema S. Krishnan、Vadim Bernard-Gauthier、Michael S. Placzek、Kenneth Dahl、Vidya Narayanaswami、Elijahu Livni、Zhen Chen、Jing Yang、Thomas L. Collier、Chongzhao Ran、Jacob M. Hooker、Steven H. Liang、Neil Vasdev

  DOI：10.1021/acs.molpharmaceut.7b00936

  日期：2018.2.5

  second generation metal protein-attenuating compound that has recently advanced in Phase II clinical trials for the treatment of AD and HD based on promising preclinical efficacy data. Herein, we report the first radiosynthesis and preclinical positron emission tomography (PET) neuroimaging evaluation of [11C]PBT2 in rodents and nonhuman primates. Carbon-11 labeled PBT2 was synthesized in 4.8 ± 0.5% (nondecay

  异位稳态或金属离子（例如铜，锌和铁）的异常蓄积与多种神经退行性疾病的发病机理有关，包括阿尔茨海默氏病（AD）和亨廷顿氏病（HD）。5,7-二氯-2-（（二甲氨基）甲基）喹啉-8-醇PBT2是第二代金属蛋白减毒化合物，基于有前途的治疗方法，最近已在II期临床试验中用于AD和HD的治疗临床前疗效数据。在此，我们报道了啮齿动物和非人类灵长类动物中[ 11 C] PBT2的首次放射合成和临床前正电子发射断层扫描（PET）神经成像评估。碳11标记的PBT2在合成结束时以[ 11 C] CH 3为基础，以4.8±0.5％（未经衰减校正）的放射化学产率（RCY）合成I（n = 6），具有高于99％的放射化学纯度和80-90 GBq /μmol的摩尔活性（A m），来自相应的甲基前体。在非人类的灵长类动物大脑中，在所有皮层和皮层下灰质区域（丘脑>尾状>皮层）白质）注射后2.5-4.5分钟内，[ 11 C]
• 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。
• Halogenated quinoline derivatives as antimicrobial agents
  申请人：University of Florida Research Foundation, Incorporated

  公开号：US11008290B2

  公开（公告）日：2021-05-18

  The present invention provides halogenated quinoline derivatives, such as compounds of Formula (I) or (I′), and pharmaceutically acceptable salts thereof, and methods of preparing the halogenated quinoline derivatives. The halogenated quinoline derivatives are expected to be antimicrobial agents and may act through an iron(II)-dependent mode of action. The present invention also provides pharmaceutical compositions, kits, uses, and methods that involve the halogenated quinoline derivatives and may be useful in preventing or treating a microbial infection (e.g., a bacterial infection) in a subject, inhibiting the growth and/or reproduction of a microorganism (e.g., a bacterium), killing a microorganism (e.g., a bacterium), inhibiting the formation and/or growth of a biofilm, reducing or removing a biofilm, and/or disinfecting a surface.

  本发明提供了卤代喹啉衍生物，如式(I)或(I′)化合物及其药学上可接受的盐，以及制备卤代喹啉衍生物的方法。卤代喹啉衍生物有望成为抗菌剂，并可能通过铁（II）依赖性作用模式发挥作用。本发明还提供了涉及卤代喹啉衍生物的药物组合物、试剂盒、用途和方法，可用于预防或治疗受试者的微生物感染（如细菌感染），抑制微生物（如细菌）的生长和/或繁殖，杀死微生物（如细菌），抑制生物膜的形成和/或生长，减少或去除生物膜，和/或消毒表面。
• Method of treating immunoglobulin light chain amyloidosis
  申请人：ALTERITY THERAPEUTICS LIMITED

  公开号：US11357770B2

  公开（公告）日：2022-06-14

  The present invention relates to the use of substituted quinoline compounds for treating immunoglobulin light chain (LC) amyloidosis (AL), especially cardiotoxicity associated with immunoglobulin LC AL. In particular, the substituted quinoline compounds useful in the treatment of cardiac LC amyloidosis are 5,7-dihalo-8-hydroxyquinoline derivatives, especially 5,7-dichloro-8-hydroxyquinoline derivatives.

  本发明涉及使用取代的喹啉化合物治疗免疫球蛋白轻链（LC）淀粉样变性（AL），特别是与免疫球蛋白LC AL相关的心脏毒性。特别是，用于治疗心脏LC淀粉样变性的取代喹啉化合物是5,7-二卤-8-羟基喹啉衍生物，尤其是5,7-二氯-8-羟基喹啉衍生物。