喹硫平杂质3 | 99153-65-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 喹硫平杂质3
• 英文名称: 4-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)piperazine
• 英文别名: 2-(2-(2-(2-(piperazin-1-yl)ethoxy)ethoxy)ethoxy)ethanol；2-[2-{2-(2-hydroxyethoxy)ethoxy}ethoxy]ethyl piperazine；2-[2-[2-(2-Piperazin-1-ylethoxy)ethoxy]ethoxy]ethanol
• CAS: 99153-65-8
• 化学式: C₁₂H₂₆N₂O₄
• 分子量: 262.349
• InChiKey: AYXJIUUSDGQMGG-UHFFFAOYSA-N

物化性质

• 沸点：
  381.1±37.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  18
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  63.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  喹硫平杂质3 在 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-(2-(2-(2-(4-(5-(4,6-diaminopyrimidin-2-ylthio)-4,6-dimethoxypyrimidin-2-yl)piperazin-1-yl)ethoxy)ethoxy)ethoxy)ethanol
  参考文献：
  名称：

  Heat Shock Protein 70 Inhibitors. 1. 2,5′-Thiodipyrimidine and 5-(Phenylthio)pyrimidine Acrylamides as Irreversible Binders to an Allosteric Site on Heat Shock Protein 70

  摘要：

  Heat shock protein 70 (Hsp70) is an important emerging. cancer. target whose inhibition may affect multiple cancer-associated signaling pathways and, moreover, result in significant cancer cell apoptosis. Despite considerable interest from both academia and pharmaceutical companies in the discovery and development of druglike Hsp70 inhibitors, little success has been reported so far. Here we describe structure activity relationship studies in the first rationally designed Hsp70 inhibitor class that binds to a novel allosteric pocket located in the N-terminal domain of the protein. These 2,5'-thiodipyrimidine and 5-(phenylthio)-pyrimidine acrylamides take advantage of an active cysteine embedded in the allosteric pocket to act as covalent protein modifiers upon binding. The study identifies derivatives 17a and 20a, which selectively bind to Hsp70 in cancer cells. Addition of high nanomolar to low micromolar concentrations of these inhibitors to cancer cells leads to a reduction in the steady-state levels of Hsp70-sheltered oncoproteins, an effect associated with inhibition of cancer cell growth and apoptosis. In summary, the described scaffolds represent a viable starting point for the development of druglike Hsp70 inhibitors as novel anticancer therapeutics.

  DOI：

  10.1021/jm401551n
• 作为产物：
  描述：

  三缩四乙二醇 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 24.5h， 生成 喹硫平杂质3
  参考文献：
  名称：

  Heat Shock Protein 70 Inhibitors. 1. 2,5′-Thiodipyrimidine and 5-(Phenylthio)pyrimidine Acrylamides as Irreversible Binders to an Allosteric Site on Heat Shock Protein 70

  摘要：

  Heat shock protein 70 (Hsp70) is an important emerging. cancer. target whose inhibition may affect multiple cancer-associated signaling pathways and, moreover, result in significant cancer cell apoptosis. Despite considerable interest from both academia and pharmaceutical companies in the discovery and development of druglike Hsp70 inhibitors, little success has been reported so far. Here we describe structure activity relationship studies in the first rationally designed Hsp70 inhibitor class that binds to a novel allosteric pocket located in the N-terminal domain of the protein. These 2,5'-thiodipyrimidine and 5-(phenylthio)-pyrimidine acrylamides take advantage of an active cysteine embedded in the allosteric pocket to act as covalent protein modifiers upon binding. The study identifies derivatives 17a and 20a, which selectively bind to Hsp70 in cancer cells. Addition of high nanomolar to low micromolar concentrations of these inhibitors to cancer cells leads to a reduction in the steady-state levels of Hsp70-sheltered oncoproteins, an effect associated with inhibition of cancer cell growth and apoptosis. In summary, the described scaffolds represent a viable starting point for the development of druglike Hsp70 inhibitors as novel anticancer therapeutics.

  DOI：

  10.1021/jm401551n

文献信息

• Radiofluorinated Pyrimidine-2,4,6-triones as Molecular Probes for Noninvasive MMP-Targeted Imaging
  作者：Hans-Jörg Breyholz、Stefan Wagner、Andreas Faust、Burkhard Riemann、Carsten Höltke、Sven Hermann、Otmar Schober、Michael Schäfers、Klaus Kopka

  DOI：10.1002/cmdc.201000013

  日期：2010.5.3

  biological targets for the specific visualization of such pathologies, in particular by using radiolabeled MMP inhibitors (MMPIs). The aim of this work was to develop a radiofluorinated molecular probe for noninvasive in vivo imaging for the detection of up‐regulated levels of activated MMPs in the living organism. Fluorinated MMPIs (26, 31 and 38) based on the pyrimidine‐2,4,6‐trione lead structure

  基质金属蛋白酶（MMP）是依赖锌和钙的内肽酶。代表甲氧西林超家族的一个亚家族，MMP参与细胞外基质成分的蛋白水解降解。MMP表达失调，MMP失调和MMP活性局部升高是各种疾病（例如癌症，动脉粥样硬化，中风，关节炎等）的共同特征。因此，活化的MMP是用于这种病理学的具体可视化的合适的生物学靶标，特别是通过使用放射性标记的MMP抑制剂（MMPI）。这项工作的目的是开发一种用于非侵入性体内成像的放射性氟化分子探针，用于检测活生物体中活化的MMP的上调水平。氟化的MMPi（26，31和38）基于嘧啶-2,4,6-三酮铅结构合成了RO 28-2653（1），并在体外评估了其对MMP的抑制力。实现了第一个18 F标记的原型MMP靶向示踪剂[ 18 F] 26的放射性合成和体内生物分布，该原型适合通过正电子发射断层扫描（PET）进行分子成像。
• HEAT SHOCK PROTEIN BINDING COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING AND USING SAME
  申请人：Chiosis Gabriela

  公开号：US20120252818A1

  公开（公告）日：2012-10-04

  The present subject matter relates to a compound represented by the general formula (I) or (I′) or a pharmacologically acceptable salt thereof; pharmaceutical compositions containing at least one of these compounds; methods of making at least one of these compounds; methods of using at least one of these compounds for treating and/or preventing various cancers and/or proliferation disorders; methods of using at least one of these compounds for monitoring the effectiveness of an anticancer therapy against various cancers. In one embodiment, the subject matter relates to compounds that bind with a level of specificity to heat shock protein 70 (Hsp70). In another embodiment, the subject matter relates to compounds that bind with a level of specificity to inhibit both heat shock protein 70 (Hsp70) and heat shock cognate protein 70 (Hsc70).

  本主题涉及一种由通式(I)或(I′)表示的化合物或其药学上可接受的盐；包含至少一种这些化合物的制药组合物；制备至少一种这些化合物的方法；使用至少一种这些化合物治疗和/或预防各种癌症和/或增殖障碍的方法；使用至少一种这些化合物监测抗癌治疗对各种癌症的有效性的方法。在一种实施方式中，本主题涉及与热休克蛋白70（Hsp70）具有特异性结合的化合物。在另一种实施方式中，本主题涉及与具有特异性抑制热休克蛋白70（Hsp70）和热休克同源蛋白70（Hsc70）的化合物的结合。
• Polymethoxybenzyl piperazine derivatives, processes for their preparation and pharmaceutical compositions containing said derivatives
  申请人：WAKO PURE CHEMICAL INDUSTRIES, LTD.

  公开号：EP0144991A2

  公开（公告）日：1985-06-19

  A compound of the formula: (R = H, CH30; n = 2 to 5) is effective for improving blood circulation system.

  式中：（R = H，CH30；n = 2 至 5）的化合物可有效改善血液循环系统。
• Heat shock protein binding compounds, compositions, and methods for making and using same
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US10052325B2

  公开（公告）日：2018-08-21

  The present subject matter relates to a compound represented by the general formula (I) or (I′) or a pharmacologically acceptable salt thereof; pharmaceutical compositions containing at least one of these compounds; methods of making at least one of these compounds; methods of using at least one of these compounds for treating and/or preventing various cancers and/or proliferation disorders; methods of using at least one of these compounds for monitoring the effectiveness of an anticancer therapy against various cancers. In one embodiment, the subject matter relates to compounds that bind with a level of specificity to heat shock protein 70 (Hsp70). In another embodiment, the subject matter relates to compounds that bind with a level of specificity to inhibit both heat shock protein 70 (Hsp70) and heat shock cognate protein 70 (Hsc70).

  本主题涉及通式(I)或(I′)代表的化合物或其药理学上可接受的盐；含有至少一种这些化合物的药物组合物；制造至少一种这些化合物的方法；使用至少一种这些化合物治疗和/或预防各种癌症和/或增殖障碍的方法；使用至少一种这些化合物监测抗癌疗法对各种癌症的疗效的方法。在一个实施方案中，该主题涉及与热休克蛋白 70（Hsp70）具有一定特异性结合的化合物。在另一个实施方案中，本发明涉及的化合物具有一定程度的特异性，可同时抑制热休克蛋白70（Hsp70）和热休克同源蛋白70（Hsc70）。
• [EN] HEAT SHOCK PROTEIN BINDING COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING AND USING SAME<br/>[FR] COMPOSÉS DE LIAISON À UNE PROTÉINE DE CHOC THERMIQUE, COMPOSITIONS ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：WO2011022440A9

  公开（公告）日：2016-11-10