2-(6-(dimethylamino)pyridin-3-yl)benzo[d]thiazol-6-ol

• 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-(6-(dimethylamino)pyridin-3-yl)benzo[d]thiazol-6-ol
• 英文别名: 2-[6-(dimethylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol
• 化学式: C₁₄H₁₃N₃OS
• 分子量: 271.343
• InChiKey: KLYGVQJZJVAHPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(6-(dimethylamino)pyridin-3-yl)benzo[d]thiazol-6-ol 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 5-(6-(2-(2-bromoethoxy)ethoxy)benzo[d]thiazol-2-yl)-N,N-dimethylpyridin-2-amine
  参考文献：
  名称：

  Oligoethyleneoxy-Modified ^99mTc-Labeled β-Amyloid Imaging Probes with Improved Brain Pharmacokinetics for Single-Photon Emission Computed Tomography

  摘要：

  An oligoethyleneoxy linker was introduced for conjugation between Tc-99m/Re-bis(aminoethanethiol) (BAT) and beta-amyloid (A beta) binding scaffolds. Rhenium complexes exhibited high to moderate binding affinity to A beta(1-42) aggregates and efficient fluorescent staining to A beta plaques in brain tissue. After radiolabeling, the Tc-99m-labeled probes revealed improved brain pharmacokinetics in normal ICR mice. Probe [Tc-99m]15 with potent binding affinity (K-i = 13.4 nM) and the highest initial brain uptake (2.10% ID/g at 2 min) in normal ICR mice was evaluated further. In vitro autoradiography showed specific labeling of A beta plaques by [Tc-99m]15 in transgenic (Tg) mouse brain tissue. Ex vivo autoradiography further demonstrated its efficient labeling of A beta plaques in a living Tg mouse. In vivo single photon emission computed tomography (SPECT)/CT imaging in six rhesus monkeys revealed remarkably improved brain uptakes (1.94-2.63% ID within 20 min) of [Tc-99m]15, making it highly potential to be used in humans for A beta plaques imaging in the brain.

  DOI：

  10.1021/acs.jmedchem.7b01834
• 作为产物：
  描述：

  5-(6-methoxybenzo[d]thiazol-2-yl)-N,N-dimethylpyridin-2-amine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以99%的产率得到2-(6-(dimethylamino)pyridin-3-yl)benzo[d]thiazol-6-ol
  参考文献：
  名称：

  用于调节和 64Cu PET 成像的 Aβ 聚集的金属螯合苯并噻唑多功能化合物

  摘要：

  虽然阿尔茨海默病 (AD) 是最常见的神经退行性疾病，但仍然缺乏针对这种疾病的有效治疗和诊断药物。本文报道了一系列新的多功能化合物 (MFC)，它们对淀粉样蛋白聚集体具有明显的亲和力，可用于调节 Aβ 聚集及其毒性，以及 Aβ 聚集体的正电子发射断层扫描 (PET) 成像。首先，在所测试的六种化合物中，HYR-16被证明能够将有毒的 Cu 介导的 Aβ 寡聚化重新路由为毒性较小的淀粉样蛋白原纤维的形成。此外，HYR-16还可以缓解由Cu 2+引起的活性氧（ROS）的形成。离子通过类芬顿反应。其次，通过与64 Cu 放射性同位素的预螯合，这些 MFC 可以很容易地转化为 PET 显像剂，并且HYR-4和HYR-17的 Cu 配合物在体外和离体都表现出良好的淀粉样斑块的荧光染色和放射性标记。重要的是，64 Cu 标记的HYR-17被证明具有高达 0.99 ± 0.04 %ID/g 的显着脑摄取。总体而言，通过评估这些

  DOI：

  10.1039/d0sc02641g

文献信息

• Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques
  作者：Mengchao Cui、Xuedan Wang、Pingrong Yu、Jinming Zhang、Zijing Li、Xiaojun Zhang、Yanping Yang、Masahiro Ono、Hongmei Jia、Hideo Saji、Boli Liu

  DOI：10.1021/jm300973k

  日期：2012.11.8

  fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel β-amyloid (Aβ) imaging probes for PET. They displayed binding affinities for Aβ1–42 aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for 18F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In

  合成了一系列氟代聚乙二醇化（FPEG）2-吡啶基苯并恶唑和2-吡啶基苯并噻唑衍生物，并将其作为PET的新型β-淀粉样（Aβ）成像探针进行了评估。他们表现出对Aβ1–42聚集体的结合亲和力，范围从2.7到101.6 nM。选择了七个具有高亲和力的配体进行18 F标记。体外放射自显影结果证实了这些放射性示踪剂的高亲和力。在正常小鼠中进行的体内生物分布实验表明，具有短FPEG链（n = 1）的放射性示踪剂显示出较高的初始摄入量并迅速从大脑中清除。2-吡啶基苯并恶唑衍生物之一，[ 18 F] -5-（5-（2-氟乙氧基）苯并[ d ]恶唑-2-基）-N-甲基吡啶-2-胺（[ 18 F] 32）（K i = 8.0±3.2 nM）的大脑2min /大脑60min之比为4.66，这对于Aβ显像剂而言是非常理想的。[ 18 F] 32与Aβ斑块的靶标特异性结合通过转基因模型小鼠的体外放射自显影实验得到验证。总体而言，[
• ^99mTc-Labeled 2-Arylbenzothiazoles: Aβ Imaging Probes with Favorable Brain Pharmacokinetics for Single-Photon Emission Computed Tomography
  作者：Xiaoyang Zhang、Pingrong Yu、Yanping Yang、Yaqin Hou、Cheng Peng、Zhigang Liang、Jing Lu、Baian Chen、Jiapei Dai、Boli Liu、Mengchao Cui

  DOI：10.1021/acs.bioconjchem.6b00444

  日期：2016.10.19

  A series of 2-arylbenzothiazole derivatives conjugated with bis(aminoethanethiol) (BAT) chelating groups were designed and synthesized. A competitive binding assay-based screening was used to select seven rhenium complexes with potent binding affinity toward Aβ1–42 aggregates (Ki < 50 nM) for 99mTc labeling and further evaluation. The 99mTc-labeled probes showed good affinity and specificity to Aβ plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [99mTc]14b exhibited favorable brain pharmacokinetics in normal mice (2.11% ID/g at 2 min and 0.62% ID/g at 60 min). Ex vivo autoradiography revealed extensive labeling of Aβ plaques by [99mTc]14b in the brain of Tg mice. Furthermore, we performed the first single-photon emission computed tomography (SPECT) imaging study in nonhuman primates with 99mTc-labeled Aβ probes. The semiquantitative data showed that [99mTc]14b penetrated the brains of rhesus monkeys. These results indicate that [99mTc]14b could be utilized as a SPECT imaging probe for Aβ plaques.

  设计并合成了一系列与双（氨基乙硫醇）螯合基团共轭的 2-芳基苯并噻唑衍生物。通过竞争性结合测定筛选出七种对 Aβ1-42 聚集体具有强结合亲和力（Ki < 50 nM）的铼复合物，用于 99mTc 标记和进一步评估。在体外自显影研究中，99m锝标记探针对Tg小鼠脑组织中的Aβ斑块具有良好的亲和力和特异性。此外，[99mTc]14b 在正常小鼠脑部的药代动力学表现良好（2 分钟内为 2.11% ID/g，60 分钟内为 0.62% ID/g）。体内外自显影显示，[99m锝]14b 在 Tg 小鼠脑中对 Aβ 斑块进行了广泛标记。此外，我们首次在非人灵长类动物中使用 99mTc 标记的 Aβ 探针进行了单光子发射计算机断层扫描（SPECT）成像研究。半定量数据显示，[99mTc]14b 能穿透恒河猴的大脑。这些结果表明，[99mTc]14b 可用作 Aβ 斑块的 SPECT 成像探针。
• Novel Heteroaryl Substituted Benzothiazoles
  申请人：Gravenfors Ylva

  公开号：US20090028787A1

  公开（公告）日：2009-01-29

  The present invention relates to novel heteroaryl substituted benzothiazole derivatives, precursors thereof, and therapeutic uses for such compounds, having the structural formula (I) below: [Chemical formula should be inserted here. Please see paper copy] and to their pharmaceutically acceptable salt, compositions and methods of use. Furthermore, the invention relates to novel heteroaryl substituted benzothiazole derivatives that are suitable for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. More specifically, the present invention relates to a method of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease as well as measuring clinical efficacy of Alzheimer's disease therapeutic agents.

  本发明涉及一种新型杂环取代苯并噻唑衍生物，其前体物和这些化合物的治疗用途，其结构式如下：[化学式应在此处插入。请参见纸质副本]以及它们的药物可接受的盐、组合物和使用方法。此外，本发明还涉及新型杂环取代苯并噻唑衍生物，适用于成像生活患者中的淀粉样沉积物，它们的组合物、使用方法和制备这些化合物的过程。更具体地，本发明涉及一种在体内成像脑中的淀粉样沉积物的方法，以允许阿尔茨海默病的临床前诊断，以及测量阿尔茨海默病治疗剂的临床疗效。
• Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for β-amyloid plaques
  作者：Britt-Marie Swahn、David Wensbo、Johan Sandell、Daniel Sohn、Can Slivo、David Pyring、Jonas Malmström、Erwan Arzel、Michaela Vallin、Margareta Bergh、Fredrik Jeppsson、Allan E. Johnson、Anders Juréus、Jan Neelissen、Samuel Svensson

  DOI：10.1016/j.bmcl.2010.01.105

  日期：2010.3

  The syntheses and SAR of new series of beta-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that it was possible to increase the signal-to-background ratios compared to PIB 1, as demonstrated by compounds 8 and 21. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and Monkey-PET Study of (<i>R</i>)- and (<i>S</i>)-¹⁸F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive <i>in Vivo</i> Kinetics
  作者：Yanping Yang、Xuedan Wang、Hui Yang、Hualong Fu、Jinming Zhang、Xiaojun Zhang、Jiapei Dai、Zhiyong Zhang、Chunping Lin、Yuzhi Guo、Mengchao Cui

  DOI：10.1021/acs.molpharmaceut.6b00643

  日期：2016.11.7

  This study describes an effective strategy to improve pharmacokinetics of A beta imaging agents, offering a novel class of (R)- and (S)-F-18-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward A beta aggregates with K-i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[F-18]28 possessed high binding potency (K-i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain(2min)/brain(60min) = 27.8) that is superior to well-established [F-18]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[F-18]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[F-18]28 clearly labeled A beta plaques both in vitro and ex vivo. These results might qualify (S)-[F-18]28 to detect A beta plaques with high signal-to-noise ratio.