2-(4-(pyrrolidin-1-yl)phenyl)-7-methoxyimidazo[2,1-b]benzothiazole | 1206722-50-0

• 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-methoxyimidazo[2,1-b]benzothiazole
• 英文别名: 2-(4-(Pyrrolidin-1-yl)phenyl)-7-methyoxyimidazo[2,1-b]benzothiazole；6-methoxy-2-(4-pyrrolidin-1-ylphenyl)imidazo[2,1-b][1,3]benzothiazole
• CAS: 1206722-50-0
• 化学式: C₂₀H₁₉N₃OS
• 分子量: 349.456
• InChiKey: HRLWBAVQUARNDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  2-氨基-6-甲氧基苯并噻唑 、 2-溴-4’-(1-吡咯烷基)苯乙酮 以to afford (295 mg, 84% yield in a purity>95%的产率得到2-(4-(pyrrolidin-1-yl)phenyl)-7-methoxyimidazo[2,1-b]benzothiazole
  参考文献：
  名称：

  Compounds for Non-Invasive Measurement of Aggregates of Amyloid Peptides

  摘要：

  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。

  公开号：

  US20120070374A1

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。
• Imaging Agents Useful for Identifying AD Pathology
  申请人：Kolb Hartmuth C.

  公开号：US20100098634A1

  公开（公告）日：2010-04-22

  Provided herein are compounds and compositions which comprise the formulae as disclosed herein, wherein the compound is an amyloid binding compound. An amyloid binding compound according to the invention may be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits, and distinguish between neurological tissue with amyloid deposits and normal neurological tissue. Amyloid probes of the invention may be used to detect and quantitate amyloid deposits in diseases including, for example, Down's syndrome, familial Alzheimer's Disease. In another embodiment, the compounds may be used in the treatment or prophylaxis of neurodegenerative disorders. Also provided herein are methods of allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing a neurodegenerative disease.

  本文提供的化合物和组合物包含如下所述的公式，其中该化合物是一种淀粉样蛋白结合化合物。本发明的淀粉样蛋白结合化合物可以以适量的方式用于体内成像淀粉样沉积物，以区分含有淀粉样沉积物的神经组织和正常神经组织。本发明的淀粉样探针可以用于检测和定量测量包括唐氏综合症、家族性阿尔茨海默病在内的疾病中的淀粉样沉积物。在另一实施例中，这些化合物可以用于治疗或预防神经退行性疾病。本文还提供了一种使化合物分布到脑组织中并成像脑组织的方法，其中与正常结合水平相比，化合物与脑组织的结合增加表明哺乳动物正在患有或有发展神经退行性疾病的风险。
• 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。
• US8420052B2
  申请人：——

  公开号：US8420052B2

  公开（公告）日：2013-04-16
• [EN] IMAGING AGENTS USEFUL FOR IDENTIFYING AD PATHOLOGY<br/>[FR] AGENTS D'IMAGERIE UTILES POUR IDENTIFIER UNE PATHOLOGIE
  申请人：SIEMENS MEDICAL SOLUTIONS

  公开号：WO2010011964A2

  公开（公告）日：2010-01-28

  Provided herein are compounds and compositions which comprise the formulae as disclosed herein, wherein the compound is an amyloid binding compound. An amyloid binding compound according to the invention may be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits, and distinguish between neurological tissue with amyloid deposits and normal neurological tissue. Amyloid probes of the invention may be used to detect and quantitate amyloid deposits in diseases including, for example, Down's syndrome, familial Alzheimer's Disease. In another embodiment, the compounds may be used in the treatment or prophylaxis of neurodegenerative disorders.. Also provided herein are methods of allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing a neurodegenerative disease.