2-(p-methylaminophenyl)-7-hydroxyimidazo[2,1-b]benzothiazole | 1240348-54-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(p-methylaminophenyl)-7-hydroxyimidazo[2,1-b]benzothiazole
• 英文别名: 2-(4-(Methylamino)phenyl)benzo[d]imidazo[2,1-b]thiazol-7-ol；2-[4-(methylamino)phenyl]imidazo[2,1-b][1,3]benzothiazol-6-ol
• CAS: 1240348-54-2
• 化学式: C₁₆H₁₃N₃OS
• 分子量: 295.365
• InChiKey: VSYPCNYTDMGCTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-溴-2-氟乙烷 、 2-(p-methylaminophenyl)-7-hydroxyimidazo[2,1-b]benzothiazole 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以78%的产率得到2-(p-methylaminophenyl)-7-(2-fluoroethoxy)imidazo[2,1-b]benzothiazole
  参考文献：
  名称：

  A Novel ¹⁸F-Labeled Imidazo[2,1-b]benzothiazole (IBT) for High-Contrast PET Imaging of β-Amyloid Plaques

  摘要：

  F-18-labeled imidazo[2,1-b]benzothiazole ([F-18]8) was synthesized and evaluated as a tracer for cerebral beta-amyloid deposits (A beta) by means of positron emission tomography (PET). [F-18]8 exhibits a high affinity to A beta and suitable brain uptake kinetics combined with a high metabolic stability in the brain. In a double transgenic APP/PS1 mouse model of Alzheimer's disease, we demonstrated a specific uptake of [F-18]8 in A beta-containing telencephalic brain regions. The specific binding of [F-18]8 to A beta was confirmed by regional brain biodistribution and autoradiography and correlated to immunohistochemistry staining. Analysis of brain sections of APP/PS1 mouse injected with a cocktail of [F-18]8 and reference compound [H-3]PiB revealed that the two tracers bind to A beta plaques in the brain of mouse in a comparable binding pattern. [F-18]8 represents the first high-contrast PET imaging agent for detection of A beta plaques in transgenic mouse model of Alzheimer's disease and holds promise for transfer to a clinical evaluation.

  DOI：

  10.1021/ml200123w
• 作为产物：
  描述：

  N-[4-(2-溴乙酰基)苯基)乙酰胺 在 三溴化硼 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-(p-methylaminophenyl)-7-hydroxyimidazo[2,1-b]benzothiazole
  参考文献：
  名称：

  A Novel ¹⁸F-Labeled Imidazo[2,1-b]benzothiazole (IBT) for High-Contrast PET Imaging of β-Amyloid Plaques

  摘要：

  F-18-labeled imidazo[2,1-b]benzothiazole ([F-18]8) was synthesized and evaluated as a tracer for cerebral beta-amyloid deposits (A beta) by means of positron emission tomography (PET). [F-18]8 exhibits a high affinity to A beta and suitable brain uptake kinetics combined with a high metabolic stability in the brain. In a double transgenic APP/PS1 mouse model of Alzheimer's disease, we demonstrated a specific uptake of [F-18]8 in A beta-containing telencephalic brain regions. The specific binding of [F-18]8 to A beta was confirmed by regional brain biodistribution and autoradiography and correlated to immunohistochemistry staining. Analysis of brain sections of APP/PS1 mouse injected with a cocktail of [F-18]8 and reference compound [H-3]PiB revealed that the two tracers bind to A beta plaques in the brain of mouse in a comparable binding pattern. [F-18]8 represents the first high-contrast PET imaging agent for detection of A beta plaques in transgenic mouse model of Alzheimer's disease and holds promise for transfer to a clinical evaluation.

  DOI：

  10.1021/ml200123w

文献信息

• Synthesis and Evaluation of ¹¹C-Labeled Imidazo[2,1-<i>b</i>]benzothiazoles (IBTs) as PET Tracers for Imaging β-Amyloid Plaques in Alzheimer’s Disease
  作者：Behrooz H. Yousefi、André Manook、Alexander Drzezga、Boris v. Reutern、Markus Schwaiger、Hans-Jürgen Wester、Gjermund Henriksen

  DOI：10.1021/jm101129a

  日期：2011.2.24

  We report a novel series of C-11-labeled imidazo[2,1-b]benzothiazoles (IBTs) as tracers for imaging of cerebral beta-amyloid (A beta) deposits in patients with Alzheimer's disease (AD) by means of positron emission tomography (PET). From a series of 11 compounds, candidates were identified to have a high binding affinity for A beta. Selected compounds were prepared as O- or N-[C-11]methyl derivatives and shown to have a high initial brain uptake in wild-type mice (range 1.9-9.2% I.D./g at 5 min). 2-(p-[C-11]Methylaminophenyl)-7-methoxyimidazo[2,1-b] benzothiazole ([C-11]5) was identified as a lead based on the combined favorable properties of high initial brain uptake, rapid clearance from normal brain, and high in vitro affinity for A beta(1-40) (K-i = 3.5 nM) and A beta(1-42) (5.8 nM), which were superior to the Pittsburgh compound B (1a). In an APP/PSI mouse model of AD (Tg), we demonstrate a specific uptake of [C-11]5 in A beta-containing telencephalic brain regions by means of small-animal PET that was confirmed by regional brain biodistribution, ex vivo autoradiography, and immunohistochemistry. Analysis of brain sections of Tg mice receiving a single bolus injection of [C-11]5 and [H-3]1a together revealed that the tracers bind to A beta plaques in the brain of Tg mice in a comparable pattern. Taken together, these data suggest that IBTs represent useful PET imaging agents for high-sensitivity detection of A beta plaques.
• A Novel ¹⁸F-Labeled Imidazo[2,1-<i>b</i>]benzothiazole (IBT) for High-Contrast PET Imaging of β-Amyloid Plaques
  作者：Behrooz H. Yousefi、Alexander Drzezga、Boris von Reutern、André Manook、Markus Schwaiger、Hans-Jürgen Wester、Gjermund Henriksen

  DOI：10.1021/ml200123w

  日期：2011.9.8

  F-18-labeled imidazo[2,1-b]benzothiazole ([F-18]8) was synthesized and evaluated as a tracer for cerebral beta-amyloid deposits (A beta) by means of positron emission tomography (PET). [F-18]8 exhibits a high affinity to A beta and suitable brain uptake kinetics combined with a high metabolic stability in the brain. In a double transgenic APP/PS1 mouse model of Alzheimer's disease, we demonstrated a specific uptake of [F-18]8 in A beta-containing telencephalic brain regions. The specific binding of [F-18]8 to A beta was confirmed by regional brain biodistribution and autoradiography and correlated to immunohistochemistry staining. Analysis of brain sections of APP/PS1 mouse injected with a cocktail of [F-18]8 and reference compound [H-3]PiB revealed that the two tracers bind to A beta plaques in the brain of mouse in a comparable binding pattern. [F-18]8 represents the first high-contrast PET imaging agent for detection of A beta plaques in transgenic mouse model of Alzheimer's disease and holds promise for transfer to a clinical evaluation.