[18F]-2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-(2-fluoroethoxy)benzoxazol | 1036395-25-1

• 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: [18F]-2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-(2-fluoroethoxy)benzoxazol
• 英文别名: (18)F-2-[2-(2-dimethylaminothiazole-5-yl)ethenyl]-6-(2-fluoroethoxy)benzoxazole
• CAS: 1036395-25-1
• 化学式: C₁₆H₁₆FN₃O₂S
• 分子量: 332.388
• InChiKey: GSZMUPHKOPBPPS-SJPDSGJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.39
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2-[2-(2-Dimethylaminothiazol-5-yl)ethenyl]-6-[2-(tosyloxy)ethoxy]benzoxazole 在 potassium [¹⁸F]fluoride 、 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 二甲基亚砜 为溶剂， 反应 0.17h， 生成 [18F]-2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-(2-fluoroethoxy)benzoxazol
  参考文献：
  名称：

  In Silico, in Vitro, and in Vivo Evaluation of New Candidates for α-Synuclein PET Imaging

  摘要：

  Accumulation of a-synuclein (alpha-syn) is a neuropathological hallmark of synucleinopathies. To date, no selective alpha-syn positron emission tomography (PET) radiotracer has been identified. Our objective was to develop the first original, selective, and specific alpha-syn PET radiotracer. Chemical design inspired from three structural families that demonstrated interesting alpha-syn binding characteristics was used as a starting point. Bioinformatics modeling of alpha-syn fibrils was then employed to select the best molecular candidates before their syntheses. An in vitro binding assay was performed to evaluate the affinity of the compounds. Radiotracer specificity and selectivity were assessed by in vitro autoradiography and in vivo PET studies in animal (rodents) models. Finally, gold standard in vitro autoradiography with patients' postmortem tissues was performed to confirm/infirm the alpha-syn binding characteristics. Two compounds exhibited a good brain availability and bound to alpha-syn and A beta fibrils in a rat model. In contrast, no signal was observed in a mouse model of synucleinopathy. Experiments in human tissues confirmed these negative results.

  DOI：

  10.1021/acs.molpharmaceut.8b00229

文献信息

• EP2103611
  申请人：——

  公开号：——

  公开（公告）日：——