2-Fluoro-4-(6-methoxy-1,3-benzothiazol-2-yl)aniline | 1026454-16-9

• 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: 2-Fluoro-4-(6-methoxy-1,3-benzothiazol-2-yl)aniline
• CAS: 1026454-16-9
• 化学式: C₁₄H₁₁FN₂OS
• 分子量: 274.319
• InChiKey: LVZGMDZAGQLWID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Fluoro-4-(6-methoxy-1,3-benzothiazol-2-yl)aniline 在 三溴化硼 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 [3H]flutemetamol
  参考文献：
  名称：

  Characterization of AZD4694, a novel fluorinated Aβ plaque neuroimaging PET radioligand

  摘要：

  J. Neurochem. (2010) 114, 784–794.AbstractPositron emission tomography (PET) radioligands that bind selectively to β‐amyloid plaques (Aβ) are promising imaging tools aimed at supporting the diagnosis of Alzheimer’s disease and the evaluation of new drugs aiming to modify amyloid plaque load. For extended clinical use, there is a particular need for PET tracers labeled with fluorine‐18, a radionuclide with 110 min half‐life allowing for central synthesis followed by wide distribution. The development of fluorinated radioligands is, however, challenging because of the lipophilic nature of aromatic fluorine, rendering fluorinated ligands more prone to have high non‐specific white matter binding. We have here developed the new benzofuran‐derived radioligand containing fluorine, AZD4694 that shows high affinity for β‐amyloid fibrils in vitro (Kd = 2.3 ± 0.3 nM). In cortical sections from human Alzheimer’s disease brain [3H]AZD4694 selectively labeled β‐amyloid deposits in gray matter, whereas there was a lower level of non‐displaceable binding in plaque devoid white matter. Administration of unlabeled AZD4694 to rat showed that it has a pharmacokinetic profile consistent with good PET radioligands, i.e., it quickly entered and rapidly cleared from normal rat brain tissue. Ex vivo binding data in aged Tg2576 mice after intravenous administration of [3H]AZD4694 showed selective binding to β‐amyloid deposits in a reversible manner. In Tg2576 mice, plaque bound [3H]AZD4694 could still be detected 80 min after i.v. administration. Taken together, the preclinical profile of AZD4694 suggests that fluorine‐18 labeled AZD4694 may have potential for PET‐visualization of cerebral β‐amyloid deposits in the living human brain.

  DOI：

  10.1111/j.1471-4159.2010.06812.x

文献信息

• Characterization of AZD4694, a novel fluorinated Aβ plaque neuroimaging PET radioligand
  作者：Anders Juréus、Britt-Marie Swahn、Johan Sandell、Fredrik Jeppsson、Allan E. Johnson、Peter Johnström、Jan A. M. Neelissen、Dan Sunnemark、Lars Farde、Samuel P. S. Svensson

  DOI：10.1111/j.1471-4159.2010.06812.x

  日期：——

  J. Neurochem. (2010) 114, 784–794.AbstractPositron emission tomography (PET) radioligands that bind selectively to β‐amyloid plaques (Aβ) are promising imaging tools aimed at supporting the diagnosis of Alzheimer’s disease and the evaluation of new drugs aiming to modify amyloid plaque load. For extended clinical use, there is a particular need for PET tracers labeled with fluorine‐18, a radionuclide with 110 min half‐life allowing for central synthesis followed by wide distribution. The development of fluorinated radioligands is, however, challenging because of the lipophilic nature of aromatic fluorine, rendering fluorinated ligands more prone to have high non‐specific white matter binding. We have here developed the new benzofuran‐derived radioligand containing fluorine, AZD4694 that shows high affinity for β‐amyloid fibrils in vitro (Kd = 2.3 ± 0.3 nM). In cortical sections from human Alzheimer’s disease brain [3H]AZD4694 selectively labeled β‐amyloid deposits in gray matter, whereas there was a lower level of non‐displaceable binding in plaque devoid white matter. Administration of unlabeled AZD4694 to rat showed that it has a pharmacokinetic profile consistent with good PET radioligands, i.e., it quickly entered and rapidly cleared from normal rat brain tissue. Ex vivo binding data in aged Tg2576 mice after intravenous administration of [3H]AZD4694 showed selective binding to β‐amyloid deposits in a reversible manner. In Tg2576 mice, plaque bound [3H]AZD4694 could still be detected 80 min after i.v. administration. Taken together, the preclinical profile of AZD4694 suggests that fluorine‐18 labeled AZD4694 may have potential for PET‐visualization of cerebral β‐amyloid deposits in the living human brain.