6-(3-[(18)F]fluoropropoxy)-2-(4-aminophenyl)-1,3-benzothiazole | 1240379-81-0

• 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: 6-(3-[(18)F]fluoropropoxy)-2-(4-aminophenyl)-1,3-benzothiazole
• 英文别名: 4-[6-(3-(18F)fluoranylpropoxy)-1,3-benzothiazol-2-yl]aniline
• CAS: 1240379-81-0
• 化学式: C₁₆H₁₅FN₂OS
• 分子量: 301.374
• InChiKey: MGQGZXGRSRDQEE-SJPDSGJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(4-aminophenyl)-6-(3-p-tosyloxypropoxy)-1,3-benzothiazole 在 氢氟酸 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 乙腈 为溶剂， 反应 0.08h， 生成 6-(3-[(18)F]fluoropropoxy)-2-(4-aminophenyl)-1,3-benzothiazole
  参考文献：
  名称：

  Synthesis and evaluation of two fluorine-18 labelled phenylbenzothiazoles as potentialin vivotracers for amyloid plaque imaging

  摘要：

  Ltd. 2009年约翰·威利父子有限公司版权所有。

  DOI：

  10.1002/jlcr.1662

文献信息

• 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。
• Synthesis and evaluation of two fluorine-18 labelled phenylbenzothiazoles as potential<i>in vivo</i>tracers for amyloid plaque imaging
  作者：K. Serdons、D. Vanderghinste、M. Van Eeckhoudt、P. Borghgraef、H. Kung、F. Van Leuven、T. de Groot、G. Bormans、A. Verbruggen

  DOI：10.1002/jlcr.1662

  日期：2009.9.15

  Uncharged derivatives of thioflavin-T have known in vitro and in vivo affinity for amyloid β. We synthesized and evaluated two derivatives with a fluorine-18 labelled fluoropropoxy substituent either at the 6-position or at the 2′-position of the 2-(4′-aminophenyl)-1,3-benzothiazole core with the aim to get suitable radiotracers to perform amyloid plaque imaging. The fluorine-18 labelled compounds were obtained by nucleophilic substitution of the corresponding tosyl precursors with [18F]fluoride with a radiochemical yield of 50%, yielding 6-(3′′-[18F]fluoropropoxy)-2-(4′-aminophenyl)-1,3-benzothiazole ([18F]2) and 2-[2′-(3′′-[18F]fluoropropoxy)-4′-aminophenyl]-1,3-benzothiazole ([18F]3) with a specific activity between 33 and 51 GBq/µmol. The identity of the radiolabelled compounds was confirmed using radio-LC-MS and by comparing retention times on RP-HPLC. Biodistribution studies in healthy mice showed for both compounds a relatively high initial brain uptake, which was significantly higher for [18F]2 than for [18F]3 (4.5% ID/g versus 3.0% ID/g, p<0.05). Wash-out from control brain was faster for [18F]3. In vitro binding affinity tests using human AD brain homogenates revealed that only compound 2 has affinity for fibrillar amyloid β (Ki=14.5 nM). This was confirmed by the incubation of transgenic APP mouse brain sections with the cold compounds, where 3 did not stain any structure whereas 2 stained amyloid plaques present in APP mouse brain. These data suggest that [18F]2 may be a useful tracer for in vivo visualization of fibrillar amyloid β. Copyright © 2009 John Wiley & Sons, Ltd.

  Ltd. 2009年约翰·威利父子有限公司版权所有。