(E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline | 1351287-52-9

• 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: (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline
• CAS: 1351287-52-9
• 化学式: C₂₁H₂₅FN₄O₃S
• 分子量: 432.519
• InChiKey: BYFWYPGZHMAEOF-OCOZRVBESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.16
• 重原子数：
  30.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.54
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  2-氨基-6-羟基苯并噻唑 在 二乙胺基三氟化硫 、 硫酸 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 异丁烯 为溶剂， 反应 11.0h， 生成 (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline
  参考文献：
  名称：

  ¹⁸F-Labeled Phenyldiazenyl Benzothiazole for in Vivo Imaging of Neurofibrillary Tangles in Alzheimer's Disease Brains

  摘要：

  We synthesized and evaluated (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a competitive ligand, FPPDB competed with ThS well and showed high affinity for both tau and A beta(1-42) aggregates (K-i = 13.0 and 20.0 nM, respectively). The results of saturation binding assays also verified that FPPDB bound to both tau and A beta(1-42) aggregates with high affinity (K-d = 44.8 nM and B-max = 45.8 pmol/nmol protein for tau aggregates and K-d = 45.4 nM and B-max = 38.9 pmol/nmol protein for A beta(1-42) aggregates). Furthermore, [F-18]FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [F-18]FPPDB displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of the chemical structure of FPPDB, further increases in selective binding to tau aggregates may lead to the development of more useful probes for the imaging of NFTs in AD brains.

  DOI：

  10.1021/ml200230e

文献信息

• ¹⁸F-Labeled Phenyldiazenyl Benzothiazole for in Vivo Imaging of Neurofibrillary Tangles in Alzheimer's Disease Brains
  作者：Kenji Matsumura、Masahiro Ono、Hiroyuki Kimura、Masashi Ueda、Yuji Nakamoto、Kaori Togashi、Yoko Okamoto、Masafumi Ihara、Ryosuke Takahashi、Hideo Saji

  DOI：10.1021/ml200230e

  日期：2012.1.12

  We synthesized and evaluated (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a competitive ligand, FPPDB competed with ThS well and showed high affinity for both tau and A beta(1-42) aggregates (K-i = 13.0 and 20.0 nM, respectively). The results of saturation binding assays also verified that FPPDB bound to both tau and A beta(1-42) aggregates with high affinity (K-d = 44.8 nM and B-max = 45.8 pmol/nmol protein for tau aggregates and K-d = 45.4 nM and B-max = 38.9 pmol/nmol protein for A beta(1-42) aggregates). Furthermore, [F-18]FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [F-18]FPPDB displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of the chemical structure of FPPDB, further increases in selective binding to tau aggregates may lead to the development of more useful probes for the imaging of NFTs in AD brains.