2-[4-(甲基氨基)苯基]-1,3-苯并噻唑-6-醇 | 566170-04-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 2-[4-(甲基氨基)苯基]-1,3-苯并噻唑-6-醇
• 英文名称: N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxybenzathiazole
• 英文别名: PiB；Pittsburgh compound B；¹¹C-PIB；(N-methyl-(11c))2-(4'-methylaminophenyl)-6-hydroxybenzothiazole；2-[4-((111C)methylamino)phenyl]-1,3-benzothiazol-6-ol
• CAS: 566170-04-5
• 化学式: C₁₄H₁₂N₂OS
• 分子量: 255.317
• InChiKey: ZQAQXZBSGZUUNL-BJUDXGSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  73.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  生成 2-[4-(甲基氨基)苯基]-1,3-苯并噻唑-6-醇
  参考文献：
  名称：

  Heteroaryl substituted benzothiazoles

  摘要：

  本发明涉及新型杂环芳基取代苯并噻唑衍生物、其前体物以及这些化合物的治疗用途，具有以下结构式（I）：[化学式应在此处插入。请参阅纸质副本]以及它们的药学上可接受的盐、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杂环芳基取代苯并噻唑衍生物、它们的组合物、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淀粉样沉积物的方法，以允许阿尔茨海默病的末期诊断以及测量阿尔茨海默病治疗药物的临床疗效。

  公开号：

  US08163928B2

文献信息

• Highlighting the versatility of the Tracerlab synthesis modules. Part 2: fully automated production of [11C]-labeled radiopharmaceuticals using a Tracerlab FXC-Pro
  作者：Xia Shao、Raphaël Hoareau、Adam C. Runkle、Louis J. M. Tluczek、Brian G. Hockley、Bradford D. Henderson、Peter J. H. Scott

  DOI：10.1002/jlcr.1937

  日期：2011.12

  Herein, we continue our series of articles showcasing the versatility of the Tracerlab FX synthesis modules by presenting straightforward, fully automated methods for preparing a range of carbon‐11 labeled radiopharmaceuticals using a Tracerlab FXC‐Pro. Strategies for production of [11C]acetate, [11C]carfentanil, [11C]choline, [11C]3‐amino‐4‐[2‐[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile ([11C]DASB)

  放射化学领域正在朝着自动合成模块的专用化方向发展，以生产临床放射药物剂量。这样的举动不仅具有许多优势，而且还给放射化学工作者带来了重新配置合成模块的挑战，以生产需要非常规放射化学同时又要保持全自动的放射性药物。在此，我们将继续介绍一系列文章，展示通过使用Tracerlab FX C-Pro制备一系列碳11标记的放射性药物的直接，全自动方法，来展示Tracerlab FX合成模块的多功能性。产生[ 11 C]乙酸盐，[ 11 C]芬太尼，[ 11 C]胆碱，[ 11C] 3-氨基-4- [2-[（（（（二（甲基）氨基）甲基]苯基]硫烷基苄腈（[ 11 C] DASB），（+）-[ 11 C]二氢萜烯嗪（[ 11 C] DTBZ） ，[ 11 C]氟马西尼（[ 11 C] FMZ），间羟基麻黄碱（[ 11 C] HED），[ 11 C]蛋氨酸，[ 11 C] PBR28，[ 11 C]匹兹堡化合物B（[
• (3-FLUORO-2-HYDROXY)PROPYL-FUNCTIONALIZED ARYL DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT FOR THE DIAGNOSIS OR TREATMENT OF NEURODEGENERATIVE BRAIN DISEASES
  申请人：Chi Dae-Yoon

  公开号：US20120214994A1

  公开（公告）日：2012-08-23

  The present invention relates to (3-fluoro-2-hydroxy)propyl-functionalized aryl derivatives or to the pharmaceutically acceptable salt thereof, to a method for preparing same, and to a pharmaceutical composition containing same as active ingredients for the diagnosis or treatment of neurodegenerative brain diseases. The aryl derivatives of the present invention are (3-fluoro-2-hydroxy)propyl-functionalized to increase the polarity thereof, and therefore the drugs containing the aryl derivatives can easily permeate into the cerebrovascular membrane, thus increasing the effectiveness of the drugs. As the aryl derivatives of the present invention strongly bind to β-amyloid, the aryl derivatives, when labeled with radioisotope, can be used as a diagnostic agent for non-invasively diagnosing early Alzheimer's disease. Further, the aryl derivatives of the present invention bind to low molecular β-amyloid peptide conjugates to inhibit the generation of malignant high molecular β-amyloid plaque, and thus can be effectively used as a therapeutic agent for neurodegenerative brain diseases such as Alzheimer's disease.

  本发明涉及（3-氟-2-羟基）丙基官能化芳基衍生物或其药用可接受的盐，以及制备该衍生物的方法，以及含有该衍生物作为活性成分的药物组合物，用于诊断或治疗神经退行性脑疾病。本发明的芳基衍生物经（3-氟-2-羟基）丙基官能化以增加其极性，因此含有该芳基衍生物的药物可以轻松渗透到脑血管膜中，从而增加药物的有效性。由于本发明的芳基衍生物与β-淀粉样蛋白结合强，因此当该芳基衍生物标记放射性同位素时，可用作无创诊断早期阿尔茨海默病的诊断剂。此外，本发明的芳基衍生物与低分子量β-淀粉样肽结合以抑制恶性高分子量β-淀粉样斑块的生成，因此可以有效用作治疗阿尔茨海默病等神经退行性脑疾病的治疗剂。
• FLUORINATED BENZOTHIAZOLE DERIVATIVES, PREPARATION METHOD THEREOF AND IMAGING AGENT FOR DIAGNOSING ALTZHEIMER'S DISEASE USING THE SAME
  申请人：Kim Sang Eun

  公开号：US20110250136A1

  公开（公告）日：2011-10-13

  The present invention relates to fluorinated benzothiazole derivatives, a preparation method thereof, and an imaging agent for diagnosing Alzheimer's disease using the same, and more particularly to fluorinated benzothiazole derivatives represented by Chemical Formula 1, derivatives of Chemical Formula 2 as a starting material for preparation thereof, a preparation method thereof, and an imaging agent for diagnosing Alzheimer's disease using fluorinated benzothiazole derivatives with a strong binding force to beta-amyloid plaque, which is a kind of biomarker for Alzheimer's disease. According to the present invention, fluorine-labeled benzothiazole derivatives, which have been difficult to synthesize by conventional methods, may be obtained by simple processes and the thus-obtained benzothiazole derivatives may be useful in diagnosing the presence and severity of Alzheimer's disease.

  本发明涉及氟代苯并噻唑衍生物，其制备方法以及利用该衍生物诊断阿尔茨海默病的成像剂，更具体地涉及化学式1所代表的氟代苯并噻唑衍生物，化学式2的衍生物作为其制备的起始材料，其制备方法，以及利用具有强结合力与β-淀粉样斑块（阿尔茨海默病的一种生物标志物）的氟代苯并噻唑衍生物诊断阿尔茨海默病的成像剂。根据本发明，通过简单的方法可获得传统方法难以合成的氟标记的苯并噻唑衍生物，所获得的苯并噻唑衍生物可用于诊断阿尔茨海默病的存在和严重程度。
• Highly efficient solid phase supported radiosynthesis of [¹¹ C]PiB using tC18 cartridge as a “3-in-1” production entity
  作者：Mehdi Boudjemeline、Robert Hopewell、Pierre-Luc Rochon、Dean Jolly、Iness Hammami、Sylvia Villeneuve、Alexey Kostikov

  DOI：10.1002/jlcr.3569

  日期：2017.12

  Pittsburgh compound B ([11C]PiB) is the gold standard positron emission tomography (PET) tracer for the in vivo imaging of amyloid plaques. Currently, it is synthesized by either solution chemistry or using a “dry loop” approach followed by HPLC purification within 30 minutes starting from [11C]CO2. Here, we report a novel, highly efficient solid phase supported carbon-11 radiolabeling procedure using commercially available disposable tC18 cartridge as a “3-in-1” entity: reactor, purifier, and solvent replacement system. [11C]PiB is synthesized by passing gaseous [11C]CH3OTf through a tC18 cartridge preloaded with a solution of precursor. Successive elution with aqueous ethanol solutions allows for nearly quantitative separation of the reaction mixture to provide chemically and radiochemically pure PET tracer. [11C]PiB suitable for human injection is produced within 10 minutes starting from [11C]CH3OTf (20 min from [11C]CO2) in 22% isolated yield not corrected for decay and molar activity of 190 GBq/μmol using 0.2 mg of precursor. This technique reduces the amount of precursor and other supplies, avoids use of preparative HPLC and toxic solvents, and decreases the time between consecutive production batches. Solid phase supported technique can facilitate [11C]PiB production compliant with Good Manufacturing Practice (GMP) and improve synthesis reliability.

  匹兹堡化合物 B（[11C]PiB）是淀粉样蛋白斑块体内成像的黄金标准正电子发射断层扫描（PET）示踪剂。目前，它是通过溶液化学或 "干循环 "方法合成的，然后在 30 分钟内从[11C]CO2 开始进行 HPLC 纯化。在此，我们报告了一种新型、高效的固相支持碳-11 放射性标记程序，该程序使用市售一次性 tC18 盒作为 "三合一 "实体：反应器、纯化器和溶剂置换系统。气态[11C]CH3OTf 通过预先装入前体溶液的 tC18 盒合成[11C]PiB。通过乙醇水溶液的连续洗脱，可以几乎定量地分离反应混合物，从而获得化学和放射化学纯 PET 示踪剂。从[11C]CH3OTf（20 分钟内从[11C]CO2）开始，在 10 分钟内就能生产出适合人体注射的[11C]PiB，分离产率为 22%（未修正衰变），摩尔活性为 190 GBq/μmol（使用 0.2 毫克前体）。该技术减少了前体和其他耗材的用量，避免了制备型高效液相色谱和有毒溶剂的使用，并缩短了连续生产批次之间的间隔时间。固相支持技术可促进符合药品生产质量管理规范（GMP）的[11C]PiB 生产，并提高合成的可靠性。
• A rapid one-step radiosynthesis of theβ-amyloid imaging radiotracerN-methyl-[11C]2-(4′-methylaminophenyl)-6-hydroxybenzothiazole([11C]-6-OH-BTA-1)
  作者：Alan A. Wilson、Armando Garcia、Alexandra Chestakova、Hank Kung、Sylvain Houle

  DOI：10.1002/jlcr.854

  日期：2004.9

  The promising β-amyloid PET imaging agent, [11C]-6-OH-BTA-1, has been radiolabelled in one step using [11C]-methyl triflate. No protection of the 6-hydroxy group is required, greatly simplifying the synthetic method. The reaction may be carried out in solution or by the captive solvent ‘loop’ method. Copyright © 2004 John Wiley & Sons, Ltd.

  [11C]-6-OH-BTA-1是一种很有前途的β淀粉样蛋白PET成像剂，采用[11C]-三酸甲酯一步法进行放射性标记。无需保护 6-羟基，大大简化了合成方法。反应可在溶液中进行，也可采用封闭溶剂 "循环 "法进行。Copyright © 2004 John Wiley & Sons, Ltd. 版权所有。