flutemetamol | 637003-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: flutemetamol
• 英文别名: 2-[3-fluoro-4-(methylamino)phenyl]-1,3-benzothiazol-6-ol
• CAS: 637003-10-2
• 化学式: C₁₄H₁₁FN₂OS
• 分子量: 274.319
• InChiKey: VVECGOCJFKTUAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 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：
  73.4
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：本记录中的信息是指将flutemetamol F 18用作诊断剂。目前没有关于在哺乳期间使用flutemetamol F 18的信息。制造商建议在给予185 MBq（5 mCi）的诊断剂量后，暂停哺乳24小时。这个时间长度大约是氟化物F 18的10个半衰期，且体内残留的放射性活度将少于0.01%。母亲可以在放射性药物给药前哺乳。如果母亲在检查前已经挤出并保存了乳汁，她可以在哺乳中断期间喂给婴儿。 担心乳汁中放射性水平的母亲可以要求在医院核医学科设施进行检测。当放射性水平达到安全水平时，她可以恢复哺乳。已经发布了一种测量乳汁放射性并确定母亲可以安全恢复哺乳的时间的方法。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Information in this record refers to the use of flutemetamol F 18 as a diagnostic agent. No information is available on the use of flutemetamol F 18 during breastfeeding. The manufacturer recommends withholding breastfeeding for 24 hours after a diagnostic dose of 185 MBq (5 mCi). This length of time is about 10 half-lives of fluoride F 18 and less than 0.01% of the radioactivity administered will remain in the body. The mother can nurse just before administration of the radiopharmaceutical. If the mother has expressed and saved milk prior to the examination, she can feed it to the infant during the period of nursing interruption. Mothers concerned about the level of radioactivity in their milk could ask to have it tested at a nuclear medicine facility at their hospital. When the radioactivity is at a safe level she may resume breastfeeding. A method for measuring milk radioactivity and determining the time when a mother can safely resume breastfeeding has been published. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为产物：
  描述：

  4-溴-2-氟-N-甲基苯胺 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 12.5h， 生成 flutemetamol
  参考文献：
  名称：

  消除杂环正电子发射断层扫描放射性配体的铜介导的 18F-氟化

  摘要：

  用氟 18 (18F) 标记的分子用于正电子发射断层扫描，以可视化、表征和测量体内的生物过程。尽管最近在将 18F 掺入芳烃方面取得了进展，但开发通用且有效的方法来标记药物发现计划所需的放射性配体仍然是一项重大任务。这个完整的描述描述了杂环正电子发射断层扫描 (PET) 放射性配体的放射合成方法，使用铜介导的 18F 氟化芳基硼试剂与 18F 氟化物作为模型反应。该方法基于一项研究，该研究检查了药物开发中常用的杂环的存在如何影响代表性芳基硼试剂的 18F-氟化效率，以及超过 50 种（杂）芳基硼酸酯的标记。这组数据允许将这种去风险策略应用于七种结构复杂的药物相关含杂环分子的成功放射合成。

  DOI：

  10.1021/jacs.7b03131

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。
• [EN] BETA-AMYLOID IMAGING AGENTS, METHODS OF MANUFACTURE, AND METHODS OF USE THEREOF<br/>[FR] AGENTS D'IMAGERIE DES BÊTA-AMYLOÏDES, SES PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：US HEALTH

  公开号：WO2013040183A1

  公开（公告）日：2013-03-21

  Derivatives of benzothiazolylbenzeneamines useful as imaging agents for nuclear imaging such as positron emission tomography of beta-amyloids are described. Methods of detecting amyloid using the compounds are described. Also disclosed is a radiolabeling method for selected compounds.

  描述了苯并噻唑基苯胺衍生物，可用作核成像的成像剂，例如正电子发射断层扫描β-淀粉样蛋白。描述了使用这些化合物检测淀粉样蛋白的方法。还公开了选定化合物的放射标记方法。
• In Vivo or in Vitro Method For Detecting Amyloid Deposits Having at Least One Amyloidogenic Protein
  申请人：Klunk William E.

  公开号：US20080305040A1

  公开（公告）日：2008-12-11

  An amyloid deposit can be detected by administering to a subject or applying to a sample a compound of Formula (I) or Formula (II) or structures 1-45, as described, and then imaging to detect binding of the compound to an amyloid deposit, where the amyloido genie protein of the deposit can be AL, AH, ATTR, Aβ2M, AA, AApoAI, AApoAII, AGeI, ALys, AFib, ACys, ABri, ADan, APrP, ACaI, AlAPP, AANF, APro, AIns, AMed, AKer, A(tbn), and/or ALac.

  通过向受试者施用或将化合物I式或II式或结构1-45应用于样本，并进行成像以检测化合物与淀粉样沉积物的结合，可以检测到淀粉样沉积物。其中，沉积物的淀粉基因蛋白可以是AL、AH、ATTR、Aβ2M、AA、AApoAI、AApoAII、AGeI、ALys、AFib、ACys、ABri、ADan、APrP、ACaI、AlAPP、AANF、APro、AIns、AMed、AKer、A(tbn)和/或ALac。
• Imaging Agents for Detecting Neurological Disorders
  申请人：Szardenings Anna Katrin

  公开号：US20110182812A1

  公开（公告）日：2011-07-28

  Imaging agents of formulas (I)-(V) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formulas (I)-(V) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formulas (I)-(V) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.

  本文介绍了公式（I）-（V）的成像剂和用于检测神经系统疾病的方法，其中包括向需要治疗的患者注射能够结合tau蛋白和β-淀粉样肽的公式（I）-（V）化合物。本发明还涉及成像Aβ和tau聚集物的方法，包括引入含有放射性标记的公式（I）-（V）化合物的制剂，并检测与淀粉样沉积物和/或tau蛋白相关联的标记化合物。这些方法和组合物可用于预临床诊断和监测AD和其他神经系统疾病的进展。
• Amyloid Imaging as a Surrogate Marker for Efficacy of Anti-Amyloid Therapies
  申请人：Klunk William E.

  公开号：US20080219931A1

  公开（公告）日：2008-09-11

  The present method for determining the efficacy of therapy in the treatment of amyloidosis involves administering to a patient in need thereof a compound of formula (I) or Formula (II) or structures 1-45 and imaging the patient. After said imaging, at least one anti-amyloid agent is administered to said patient. Then, an effective amount of a compound of formula (I) or Formula (II) or structures 1-45 is administered to the patient and the patient is imaged again. Finally, baseline levels of amyloid deposition in the patient before treatment with the anti-amyloid agent are compared with levels of amyloid deposition in the patient following treatment with the anti-amyloid agent.

  目前用于确定淀粉样变性治疗疗效的方法包括向需要治疗的患者给予式（I）或式（II）或结构1-45的化合物，并对患者进行成像。在成像后，向该患者至少给予一种抗淀粉样蛋白药物。然后，向患者有效剂量的式（I）或式（II）或结构1-45的化合物，并再次对患者进行成像。最后，比较抗淀粉样蛋白药物治疗前患者的淀粉样沉积基线水平和治疗后患者的淀粉样沉积水平。