2-(4-bromomethylphenoxy)ethyl 4-methylbenzenesulfonate | 1343413-04-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-bromomethylphenoxy)ethyl 4-methylbenzenesulfonate
• 英文别名: 2-[4-(Bromomethyl)phenoxy]ethyl 4-methylbenzenesulfonate；2-[4-(bromomethyl)phenoxy]ethyl 4-methylbenzenesulfonate
• CAS: 1343413-04-6
• 化学式: C₁₆H₁₇BrO₄S
• 分子量: 385.279
• InChiKey: WKWCFBCHZVLAPY-UHFFFAOYSA-N

物化性质

• 沸点：
  513.3±40.0 °C(Predicted)
• 密度：
  1.436±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-bromomethylphenoxy)ethyl 4-methylbenzenesulfonate 在 palladium-on-charcoal 氢气 、 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， -10.0~75.0 ℃ 、490.34 kPa 条件下， 反应 15.5h， 生成 1-[[4-[2-(氮杂环庚烷-1-基)乙氧基]苯基]甲基]-2-(4-羟基苯基)-3-甲基-吲哚-5-醇
  参考文献：
  名称：

  NOVEL PROCESS FOR THE PREPARATION OF BAZEDOXIFENE ACETATE AND INTERMEDIATES THEREOF

  摘要：

  描述了一种用于制备药用化合物的新工艺，例如通常称为贝泽度西酚醋酸盐的1-{4-[2-(azepan-1-yl)ethoxy]benzyl}-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol乙酸的化学式-1，使用2-(4-{[5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indol-1-yl]methyl}phenoxy)ethyl-4-methylbenzenzene-1-sulfonate (化学式2a)。

  公开号：

  US20120330008A1
• 作为产物：
  描述：

  4-(2-羟基乙氧基)苯甲醛 在 sodium tetrahydroborate 、 三溴化磷 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 13.25h， 生成 2-(4-bromomethylphenoxy)ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  NOVEL PROCESS FOR THE PREPARATION OF BAZEDOXIFENE ACETATE AND INTERMEDIATES THEREOF

  摘要：

  描述了一种用于制备药用化合物的新工艺，例如通常称为贝泽度西酚醋酸盐的1-{4-[2-(azepan-1-yl)ethoxy]benzyl}-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol乙酸的化学式-1，使用2-(4-{[5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indol-1-yl]methyl}phenoxy)ethyl-4-methylbenzenzene-1-sulfonate (化学式2a)。

  公开号：

  US20120330008A1

文献信息

• Initial biological evaluations of 18F-KS1, a novel ascorbate derivative to image oxidative stress in cancer
  作者：Kiran Kumar Solingapuram Sai、Nagaraju Bashetti、Xiaofei Chen、Skylar Norman、Justin W. Hines、Omsai Meka、J. V. Shanmukha Kumar、Sriram Devanathan、Gagan Deep、Cristina M. Furdui、Akiva Mintz

  DOI：10.1186/s13550-019-0513-x

  日期：2019.12

  Reactive oxygen species (ROS)-induced oxidative stress damages many cellular components such as fatty acids, DNA, and proteins. This damage is implicated in many disease pathologies including cancer and neurodegenerative and cardiovascular diseases. Antioxidants like ascorbate (vitamin C, ascorbic acid) have been shown to protect against the deleterious effects of oxidative stress in patients with cancer. In contrast, other data indicate potential tumor-promoting activity of antioxidants, demonstrating a potential temporal benefit of ROS. However, quantifying real-time tumor ROS is currently not feasible, since there is no way to directly probe global tumor ROS. In order to study this ROS-induced damage and design novel therapeutics to prevent its sequelae, the quantitative nature of positron emission tomography (PET) can be harnessed to measure in vivo concentrations of ROS. Therefore, our goal is to develop a novel translational ascorbate-based probe to image ROS in cancer in vivo using noninvasive PET imaging of tumor tissue. The real-time evaluations of ROS state can prove critical in developing new therapies and stratifying patients to therapies that are affected by tumor ROS. We designed, synthesized, and characterized a novel ascorbate derivative (E)-5-(2-chloroethylidene)-3-((4-(2-fluoroethoxy)benzyl)oxy)-4-hydroxyfuran-2(5H)-one (KS1). We used KS1 in an in vitro ROS MitoSOX-based assay in two different head and neck squamous cancer cells (HNSCC) that express different ROS levels, with ascorbate as reference standard. We radiolabeled 18F-KS1 following 18F-based nucleophilic substitution reactions and determined in vitro reactivity and specificity of 18F-KS1 in HNSCC and prostate cancer (PCa) cells. MicroPET imaging and standard biodistribution studies of 18F-KS1 were performed in mice bearing PCa cells. To further demonstrate specificity, we performed microPET blocking experiments using nonradioactive KS1 as a blocker. KS1 was synthesized and characterized using 1H NMR spectra. MitoSOX assay demonstrated good correlations between increasing concentrations of KS1 and ascorbate and increased reactivity in SCC-61 cells (with high ROS levels) versus rSCC-61cells (with low ROS levels). 18F-KS1 was radiolabeled with high radiochemical purity (> 94%) and specific activity (~ 100 GBq/μmol) at end of synthesis (EOS). Cell uptake of 18F-KS1 was high in both types of cancer cells, and the uptake was significantly blocked by nonradioactive KS1, and the ROS blocker, superoxide dismutase (SOD) demonstrating specificity. Furthermore, 18F-KS1 uptake was increased in PCa cells under hypoxic conditions, which have been shown to generate high ROS. Initial in vivo tumor uptake studies in PCa tumor-bearing mice demonstrated that 18F-KS1 specifically bound to tumor, which was significantly blocked (threefold) by pre-injecting unlabeled KS1. Furthermore, biodistribution studies in the same tumor-bearing mice showed high tumor to muscle (target to nontarget) ratios. This work demonstrates the strong preliminary support of 18F-KS1, both in vitro and in vivo for imaging ROS in cancer. If successful, this work will provide a new paradigm to directly probe real-time oxidative stress levels in vivo. Our work could enhance precision medicine approaches to treat cancer, as well as neurodegenerative and cardiovascular diseases affected by ROS.

  活性氧（ROS）诱导的氧化应激会损害许多细胞成分，如脂肪酸、DNA 和蛋白质。这种损伤与癌症、神经退行性疾病和心血管疾病等多种疾病病理有关。抗氧化剂，如抗坏血酸（维生素 C，抗坏血酸），已被证明能保护癌症患者免受氧化应激的有害影响。与此相反，其他数据表明抗氧化剂具有潜在的肿瘤促进活性，显示了 ROS 潜在的时间益处。然而，目前对肿瘤 ROS 进行实时量化并不可行，因为没有办法直接探测肿瘤的整体 ROS。为了研究这种由 ROS 引发的损伤并设计新型疗法来防止其后遗症，可以利用正电子发射断层扫描（PET）的定量特性来测量体内 ROS 的浓度。因此，我们的目标是开发一种基于抗坏血酸盐的新型转化探针，利用肿瘤组织的无创 PET 成像对体内癌症中的 ROS 进行成像。对 ROS 状态的实时评估对于开发新的疗法和对受肿瘤 ROS 影响的患者进行分层治疗至关重要。我们设计、合成并鉴定了一种新型抗坏血酸衍生物 (E)-5-(2-chloroethylidene)-3-((4-(2-fluoroethoxy)benzyl)oxy)-4-hydroxyfuran-2(5H)-one (KS1)。我们使用 KS1 在两种不同的头颈部鳞癌细胞（HNSCC）中进行了基于 ROS MitoSOX 的体外检测，这两种细胞表达的 ROS 水平不同，抗坏血酸是参考标准。我们通过基于 18F 的亲核取代反应对 18F-KS1 进行了放射性标记，并确定了 18F-KS1 在 HNSCC 和前列腺癌 (PCa) 细胞中的体外反应性和特异性。我们在携带 PCa 细胞的小鼠体内进行了 18F-KS1 的 MicroPET 成像和标准生物分布研究。为了进一步证明特异性，我们使用非放射性 KS1 作为阻断剂进行了 microPET 阻断实验。我们利用 1H NMR 光谱合成并鉴定了 KS1。MitoSOX 分析表明，KS1 和抗坏血酸浓度的增加与 SCC-61 细胞（ROS 水平高）和 rSCC-61 细胞（ROS 水平低）反应性的增加之间存在良好的相关性。18F-KS1 的放射标记具有较高的放射化学纯度（> 94%）和合成末期（EOS）的比活度（约 100 GBq/μmol）。两种癌细胞对 18F-KS1 的摄取量都很高，而非放射性 KS1 和 ROS 阻断剂超氧化物歧化酶（SOD）都能显著阻断细胞对 18F-KS1 的摄取，证明了其特异性。此外，在缺氧条件下，PCa 细胞对 18F-KS1 的摄取也会增加，而缺氧会产生大量 ROS。对携带 PCa 肿瘤的小鼠进行的初步体内肿瘤摄取研究表明，18F-KS1 能特异性地与肿瘤结合，而预先注射未标记的 KS1 则能显著阻断这种结合（三倍）。此外，在同样的肿瘤小鼠中进行的生物分布研究显示，肿瘤与肌肉（靶与非靶）的比例很高。这项工作表明，18F-KS1 在体外和体内对癌症中的 ROS 成像具有强有力的初步支持。如果这项工作取得成功，将为直接探测体内实时氧化应激水平提供一个新的范例。我们的工作可以加强精准医学方法，以治疗受 ROS 影响的癌症、神经退行性疾病和心血管疾病。
• COMPOUNDS AND COMPOSITIONS USEFUL AS RADIOTRACERS FOR IMAGING OF REACTIVE OXIDATIVE SPECIES
  申请人：Wake Forest University Health Sciences

  公开号：US20200316229A1

  公开（公告）日：2020-10-08

  Provided herein are compounds and compositions useful for imaging, detecting, and/or diagnosing oxidative stress and/or a ROS modulated illness by detection of gamma radiation emitted by the compound, as well as intermediate compounds and methods useful to make the compounds and/or compositions, and methods of use thereof.

  本文提供了一些化合物和组合物，可用于通过检测化合物所发射的伽马辐射来成像、检测和/或诊断氧化应激和/或ROS调节的疾病，以及制备这些化合物和/或组合物的中间体和方法，以及它们的使用方法。
• US8889896B2
  申请人：——

  公开号：US8889896B2

  公开（公告）日：2014-11-18
• NOVEL PROCESS FOR THE PREPARATION OF BAZEDOXIFENE ACETATE AND INTERMEDIATES THEREOF
  申请人：Divi Murali Krishna Prasad

  公开号：US20120330008A1

  公开（公告）日：2012-12-27

  A novel process is described for the preparation of pharmaceutically useful compounds such as 1-4-[2-(azepan-1-yl)ethoxy]benzyl}-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol acetic acid commonly known as bazedoxifene acetate of the formula-1 using 2-(4-[5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indol-1-yl]methyl}phenoxy)ethyl-4-methylbenzenzene-1-sulfonate (formula 2a)

  描述了一种用于制备药用化合物的新工艺，例如通常称为贝泽度西酚醋酸盐的1-4-[2-(azepan-1-yl)ethoxy]benzyl}-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol乙酸的化学式-1，使用2-(4-[5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indol-1-yl]methyl}phenoxy)ethyl-4-methylbenzenzene-1-sulfonate (化学式2a)。