2-(4-aminophenyl)-6-(3-p-tosyloxypropoxy)-1,3-benzothiazole | 1197241-40-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-aminophenyl)-6-(3-p-tosyloxypropoxy)-1,3-benzothiazole
• 英文别名: 6-(3-p-tosyloxypropoxy)-2-(4-aminophenyl)-1,3-benzothiazole；3-[[2-(4-Aminophenyl)-1,3-benzothiazol-6-yl]oxy]propyl 4-methylbenzenesulfonate
• CAS: 1197241-40-9
• 化学式: C₂₃H₂₂N₂O₄S₂
• 分子量: 454.571
• InChiKey: MDNJYRFMGAKZSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1,3-丙二醇-二-间-甲苯磺酸盐 、 6-苯并噻唑醇 在 sodium methylate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 12.0h， 以26.3%的产率得到2-(4-aminophenyl)-6-(3-p-tosyloxypropoxy)-1,3-benzothiazole
  参考文献：
  名称：

  Synthesis and evaluation of two uncharged^99mTc-labeled derivatives of thioflavin-T as potential tracer agents for fibrillar brain amyloid

  摘要：

  硫黄素-T 是一种荧光染料，可用于体外检测阿尔茨海默病患者大脑中的纤维状淀粉样蛋白 β。我们合成了两种不带电荷的 99mTc 标记的硫黄素-T 衍生物，并对其进行了生物学评估。用于标记的前体是通过丙氧基间隔物将 S,S′-双-三苯甲基-N-叔丁氧羰基双-氨基-双-硫醇四价配体与 2-(4′-氨基苯基)-1,3-苯并噻唑的 6 位或 2′位偶联而合成的。99m锝的去保护和标记是通过一锅法完成的（收率为 15%），然后用高效液相色谱法（LC）分离出标记化合物。液相色谱法与质谱法相结合，用于确认标记化合物的身份。电泳和对数 P 测定的结果支持了放射性标记化合物可通过被动扩散穿过血脑屏障的假设。然而，在正常小鼠体内，两种化合物在注射后 2 分钟的脑吸收率都很低。它们主要通过肝胆系统排出体外，在胃中也有一些蓄积。静脉注射 60 分钟后，血液中 37% 的 99mTc 活性与原始化合物一致。鉴于大脑摄取量较低，结论是所研究的 99mTc 标记的硫黄素-T 衍生物不适合作为体内观察大脑淀粉样蛋白的示踪剂。版权所有 © 2009 约翰威利父子有限公司。

  DOI：

  10.1002/jlcr.1592

文献信息

• Synthesis and evaluation of two uncharged^99mTc-labeled derivatives of thioflavin-T as potential tracer agents for fibrillar brain amyloid
  作者：K. Serdons、D. Vanderghinste、M. Van Eeckhoudt、J. Cleynhens、T. de Groot、G. Bormans、A. Verbruggen

  DOI：10.1002/jlcr.1592

  日期：2009.5.30

  Thioflavin-T is a fluorescent dye for in vitro detection of fibrillar amyloid β, a protein found in the brain of patients suffering from Alzheimer's disease. We synthesized and biologically evaluated two uncharged 99mTc-labeled derivatives of thioflavin-T. The precursors for labeling were synthesized by coupling an S,S′-bis-triphenylmethyl-N-tert-butoxycarbonyl bis-amino-bis-thiol tetradentate ligand via a propoxy spacer to 2-(4′-aminophenyl)-1,3-benzothiazole at the 6-position or the 2′-position. Deprotection and labeling with 99mTc were done via a one-pot procedure (15% yield) after which the labeled compound was isolated by high performance liquid chromatography (LC). LC in combination with mass spectrometry (MS) was used for identity confirmation of the labeled compounds. Results of electrophoresis and log P determination supported the assumption that the radiolabeled compounds could cross the blood–brain barrier by passive diffusion. However, in normal mice both compounds showed a low brain uptake 2 min post injection. They were mainly excreted through the hepatobiliary system, with some accumulation in the stomach. Sixty minutes after intravenous injection, 37% of the 99mTc-activity in the blood corresponded to the original compound. In view of the low brain uptake, it is concluded that the studied 99mTc-labeled derivatives of thioflavin-T are not suitable as tracer agents for in vivo visualization of amyloid in brain. Copyright © 2009 John Wiley & Sons, Ltd.

  硫黄素-T 是一种荧光染料，可用于体外检测阿尔茨海默病患者大脑中的纤维状淀粉样蛋白 β。我们合成了两种不带电荷的 99mTc 标记的硫黄素-T 衍生物，并对其进行了生物学评估。用于标记的前体是通过丙氧基间隔物将 S,S′-双-三苯甲基-N-叔丁氧羰基双-氨基-双-硫醇四价配体与 2-(4′-氨基苯基)-1,3-苯并噻唑的 6 位或 2′位偶联而合成的。99m锝的去保护和标记是通过一锅法完成的（收率为 15%），然后用高效液相色谱法（LC）分离出标记化合物。液相色谱法与质谱法相结合，用于确认标记化合物的身份。电泳和对数 P 测定的结果支持了放射性标记化合物可通过被动扩散穿过血脑屏障的假设。然而，在正常小鼠体内，两种化合物在注射后 2 分钟的脑吸收率都很低。它们主要通过肝胆系统排出体外，在胃中也有一些蓄积。静脉注射 60 分钟后，血液中 37% 的 99mTc 活性与原始化合物一致。鉴于大脑摄取量较低，结论是所研究的 99mTc 标记的硫黄素-T 衍生物不适合作为体内观察大脑淀粉样蛋白的示踪剂。版权所有 © 2009 约翰威利父子有限公司。
• 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。