2-(4-(pyrrolidin-1-yl)phenyl)-7-hydroxyimidazo[2,1-b]benzothiazole | 1240348-41-7

• 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-(4-(pyrrolidin-1-yl)phenyl)-7-hydroxyimidazo[2,1-b]benzothiazole
• 英文别名: 2-(4-Pyrrolidin-1-ylphenyl)imidazo[2,1-b][1,3]benzothiazol-6-ol
• CAS: 1240348-41-7
• 化学式: C₁₉H₁₇N₃OS
• 分子量: 335.429
• InChiKey: HQMZHKLTRNSAEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 2-(4-(pyrrolidin-1-yl)phenyl)-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 0.16h， 生成 6-(111C)methoxy-2-(4-pyrrolidin-1-ylphenyl)imidazo[2,1-b][1,3]benzothiazole
  参考文献：
  名称：

  Synthesis and Evaluation of ¹¹C-Labeled Imidazo[2,1-b]benzothiazoles (IBTs) as PET Tracers for Imaging β-Amyloid Plaques in Alzheimer’s Disease

  摘要：

  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.

  DOI：

  10.1021/jm101129a
• 作为产物：
  描述：

  2-(4-(pyrrolidin-1-yl)phenyl)-7-methoxyimidazo[2,1-b]benzothiazole 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以88%的产率得到2-(4-(pyrrolidin-1-yl)phenyl)-7-hydroxyimidazo[2,1-b]benzothiazole
  参考文献：
  名称：

  Synthesis and Evaluation of ¹¹C-Labeled Imidazo[2,1-b]benzothiazoles (IBTs) as PET Tracers for Imaging β-Amyloid Plaques in Alzheimer’s Disease

  摘要：

  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.

  DOI：

  10.1021/jm101129a

文献信息

• Compounds for non-invasive measurement of aggregates of amyloid peptides
  申请人：Technische Universität München

  公开号：EP2218464A1

  公开（公告）日：2010-08-18

  The invention relates to the provision of compounds, methods for producing them, and their use for imaging and quantification of aggregates of amyloid peptides in vivo. In a preferred aspect of the invention, a tracer is administered to humans and displays enrichment in the areas that are containing amyloid plaques. Tracers of the invention can be used for in vivo visualization and quantification of aggregates of amyloid peptides in patients affected diseases characterized in the generation of aggregates of amyloid peptides, for example familial or sporadic Alzheimer's disease and type II diabetes. Tracers of the invention can be used for monitoring effects of amyloid-modulating therapies of patients affected with diseases characterized in the generation of aggregates of amyloid peptides, for example familial or sporadic Alzheimer's disease and type II diabetes.

  该发明涉及化合物的提供、生产方法以及它们在体内成像和定量淀粉样肽聚集物的用途。在该发明的一个优选方面，向人类施用一种示踪剂，并且在含有淀粉样斑块的区域显示富集。该发明的示踪剂可用于患有以生成淀粉样肽聚集物为特征的疾病的患者体内成像和定量，例如家族性或散发性阿尔茨海默病和2型糖尿病。该发明的示踪剂可用于监测患有以生成淀粉样肽聚集物为特征的疾病的患者对调节淀粉样蛋白的疗法的影响，例如家族性或散发性阿尔茨海默病和2型糖尿病。
• Compounds for Non-Invasive Measurement of Aggregates of Amyloid Peptides
  申请人：Gjermund Henriksen

  公开号：US20120070374A1

  公开（公告）日：2012-03-22

  The invention relates to the provision of compounds, methods for producing them, and their use for imaging and quantification of aggregates of β-amyloid peptides in vivo. In a preferred aspect of the invention, a tracer is administered to humans and displays enrichment in body parts that are containing aggregates of amyloid peptides. Tracers of the invention can be used for non-invasive depiction and quantification of aggregates of β-amyloid peptides in humans affected with diseases that are characterized in the generation of such aggregates.

  本发明涉及提供化合物、制备它们的方法以及它们在体内成像和量化β-淀粉样肽聚集物的使用。在本发明的一个优选方面，向人体注射示踪剂，并在含有淀粉样肽聚集物的身体部位显示富集。本发明的示踪剂可用于非侵入性地描绘和量化患有生成此类聚集物的疾病的人体内β-淀粉样肽聚集物。
• [EN] COMPOUNDS FOR NON-INVASIVE MEASUREMENT OF AGGREGATES OF AMYLOID PEPTIDES<br/>[FR] COMPOSÉS POUR LA MESURE NON VULNÉRANTE D'AGRÉGATS DE PEPTIDES AMYLOÏDES
  申请人：UNIV MUENCHEN TECH

  公开号：WO2010092111A2

  公开（公告）日：2010-08-19

  The invention relates to the provision of compounds, methods for producing them, and their use for imaging and quantification of aggregates of β-amyloid peptides in vivo. In a preferred aspect of the invention, a tracer is administered to humans and displays enrichment in body parts that are containing aggregates of amyloid peptides. Tracers of the invention can be used for non-invasive depiction and quantification of aggregates of β-amyloid peptides in humans affected with diseases that are characterized in the generation of such aggregates.
• 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.