(Z)-2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole | 1352300-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: (Z)-2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole
• 英文别名: 4-[(Z)-2-(1,3-benzoxazol-2-yl)ethenyl]-N-(2-fluoroethyl)-N-methylaniline
• CAS: 1352300-06-1
• 化学式: C₁₈H₁₇FN₂O
• 分子量: 296.344
• InChiKey: STINMKQPTUMWHK-FLIBITNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  29.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯甲基-1,3-苯并恶唑 在 potassium tert-butylate 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 甲苯 、 苯 为溶剂， 反应 0.5h， 生成 (Z)-2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole
  参考文献：
  名称：

  Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes

  摘要：

  The formation of proteinaceous aggregates is a pathognomonic hallmark of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. To date, the final diagnostic for these diseases can only be achieved by immunostaining of post-mortem brain tissues with the commonly used congo red and Thioflavin T/S amyloid-dyes. The interest in developing amyloid-avid radioprobes to be used for protein aggregates imaging by positron emission tomography has grown substantialy, due to the promise in assisting diagnosis of these disorders. To this purpose, the present work describes the synthesis and characterization of four novel fluorinated styryl benzazole derivatives 1-4 by means of the Wittig reaction, as well as their in vitro evaluation as amyloid-probing agents. All compounds were obtained as mixtures of geometric E and Z isomers, with the preferable formation of the E isomer. Photoisomerization reactions allowed for the maximization of the minor Z isomers. The authentic 1-4E/Z isomers were isolated after purification by column chromatography under dark conditions. Profiting from the fluorescence properties of the different geometric isomers of 1-4, their binding affinities towards amyloid fibrils of insulin, alpha-synuclein and beta-amyloid peptide were also measured. These compounds share similarities with Thioflavin T, interacting specifically with fibrillary species with a red-shift in the excitation wavelengths along with an increase in the fluorescence emission intensity. Apparent binding constants were determined and ranged between 1.22 and 23.96 mu M-1. The present data suggest that the novel fluorinated styryl benzazole derivatives may prove useful for the design of F-18-labeled amyloid radioprobes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.065

文献信息

• Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes
  作者：Goreti Ribeiro Morais、Hugo Vicente Miranda、Isabel C. Santos、Isabel Santos、Tiago F. Outeiro、Antonio Paulo

  DOI：10.1016/j.bmc.2011.09.065

  日期：2011.12

  The formation of proteinaceous aggregates is a pathognomonic hallmark of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. To date, the final diagnostic for these diseases can only be achieved by immunostaining of post-mortem brain tissues with the commonly used congo red and Thioflavin T/S amyloid-dyes. The interest in developing amyloid-avid radioprobes to be used for protein aggregates imaging by positron emission tomography has grown substantialy, due to the promise in assisting diagnosis of these disorders. To this purpose, the present work describes the synthesis and characterization of four novel fluorinated styryl benzazole derivatives 1-4 by means of the Wittig reaction, as well as their in vitro evaluation as amyloid-probing agents. All compounds were obtained as mixtures of geometric E and Z isomers, with the preferable formation of the E isomer. Photoisomerization reactions allowed for the maximization of the minor Z isomers. The authentic 1-4E/Z isomers were isolated after purification by column chromatography under dark conditions. Profiting from the fluorescence properties of the different geometric isomers of 1-4, their binding affinities towards amyloid fibrils of insulin, alpha-synuclein and beta-amyloid peptide were also measured. These compounds share similarities with Thioflavin T, interacting specifically with fibrillary species with a red-shift in the excitation wavelengths along with an increase in the fluorescence emission intensity. Apparent binding constants were determined and ranged between 1.22 and 23.96 mu M-1. The present data suggest that the novel fluorinated styryl benzazole derivatives may prove useful for the design of F-18-labeled amyloid radioprobes. (C) 2011 Elsevier Ltd. All rights reserved.