4-(7-methoxybenzo[d]imidazo[2,1-b]thiazol-2-yl)aniline | 1206722-59-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(7-methoxybenzo[d]imidazo[2,1-b]thiazol-2-yl)aniline
• 英文别名: 4-(7-Methoxyimidazo[2,1-b]benzothiazol-2-yl)-benzenamine；4-(6-methoxyimidazo[2,1-b][1,3]benzothiazol-2-yl)aniline
• CAS: 1206722-59-9
• 化学式: C₁₆H₁₃N₃OS
• 分子量: 295.365
• InChiKey: KHYLQHLGCZVNML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 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：
  80.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(7-methoxybenzo[d]imidazo[2,1-b]thiazol-2-yl)aniline 在 三溴化硼 、 sodium hydride 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 生成 [18F]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 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 4-(7-methoxybenzo[d]imidazo[2,1-b]thiazol-2-yl)aniline
  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
• 作为试剂：
  描述：

  2-氨基-6-甲氧基苯并噻唑 、 2-溴-4'-硝基苯乙酮 、 、 氯化亚锡 在 乙醚 、 7-methoxy-2-(4-nitrophenyl)benzo[d]imidazo[2,1-b]thiazole 、 氮 、 sodium hydroxide 、 Sodium sulfate-III 、 crude product 、 4-(7-methoxybenzo[d]imidazo[2,1-b]thiazol-2-yl)aniline 、 甲醇 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 4-(7-methoxybenzo[d]imidazo[2,1-b]thiazol-2-yl)aniline
  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

• Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors
  作者：Qing Zhang、Kuantao Zhao、Lixun Zhang、Xiaoyu Jiao、Yongjie Zhang、Chunlei Tang

  DOI：10.1016/j.bmcl.2020.127525

  日期：2020.12

  tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in a low nanomolar range. In particular, compound 16b demonstrated significant inhibitory potency against FLT3-ITD

  作为III类受体酪氨酸激酶（RTK），FMS样酪氨酸激酶3（FLT3）在许多急性白血病病例中总是过表达。本文研究了二芳基脲衍生物作为FLT3抑制剂的结构化合成和生物学评价。令人鼓舞的是，化合物15b，16b，24a和24c在低纳摩尔范围内显示出出色的生物活性。特别地，化合物16b表现出对FLT3-ITD的显着抑制作用（IC 50＝ 5.60nM），并且比奎扎替尼对MV4-11细胞系具有更好的抗增殖活性（IC 50＝0.176nM ）。表明化合物16b 对于急性髓细胞白血病的治疗可能非常有前途。
• 一种苯并咪唑并[2,1-b]噻唑类化合物及其应 用
  申请人：江南大学

  公开号：CN111362972B

  公开（公告）日：2021-08-24

  本发明公开了一种苯并咪唑并[2,1‑b]噻唑类化合物及其应用，属于医药技术领域。本发明中合成的苯并咪唑并[2,1‑b]噻唑类似物对FLT3的抑制活性达到90％以上，其中，化合物(化合物2、4、6、8和10)对FLT3‑ITD激酶的IC50值较低，特别是化合物2，其IC50值仅为5.60nM，因此，本发明的化合物可以被用作FLT3的抑制剂，或者用来制备药物，所述药物能够通过影响一种或多种酪氨酸激酶的酶活性并干扰由所述激酶转导的信号来调节或抑制与异常细胞增殖相关的疾病，具有广阔的应用前景。
• 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。
• 2-Arylimidazo[2,1-b]benzothiazoles: A new family of amyloid binding agents with potential for PET and SPECT imaging of Alzheimer’s brain
  作者：David Alagille、Herve DaCosta、Ronald M. Baldwin、Gilles D. Tamagnan

  DOI：10.1016/j.bmcl.2011.03.052

  日期：2011.5

  We designed and synthesized a small series of 2-aryl-imidazo[2,1-b]benzothiazole, representing a combination of motifs from the two most potent amyloid imaging agents, PIB and IMPY. The binding affinity of the new compounds ranged from 6 to 133 nM. Among the best compounds, 3b (K-i = 6 nM) can be labeled with (CH3)-C-11 for PET imaging whereas 3j (K-i = 10.9 nM) can be labeled with I-123 for SPECT imaging. (C) 2011 Elsevier Ltd. All rights reserved.