(4-氯甲基)香豆素-7-氨基甲酸乙酯 | 147963-30-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: (4-氯甲基)香豆素-7-氨基甲酸乙酯
• 英文名称: [4-(chloromethyl)-2-oxo-2H-1-benzopyran-7-yl]-carbamic acid ethyl ester
• 英文别名: ethyl (4-(chloromethyl)-2-oxo-2H-benzopyran-7-yl)carbamate；ethyl (4-(chloromethyl)-2-oxo-2H-chromen-7-yl)carbamate；N-ethoxycarbonyl-7-amino-4-chloromethylcoumarin；4-chloromethyl-2-oxo-2H-chromen-7-yl-carbamic acid ethyl ester；7-carbethoxyamino-4-chloromethylcoumarin；ethyl N-[4-(chloromethyl)-2-oxo-2H-chromen-7-yl]carbamate；ethyl N-[4-(chloromethyl)-2-oxochromen-7-yl]carbamate
• CAS: 147963-30-2
• 化学式: C₁₃H₁₂ClNO₄
• mdl: MFCD03988535
• 分子量: 281.696
• InChiKey: IVDPVMAMQUEQNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-氯甲基)香豆素-7-氨基甲酸乙酯 在 硫酸 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 20.0h， 生成 7-amino-4-((2-methyl-4-nitro-1H-imidazol-1-yl)methyl)coumarin
  参考文献：
  名称：

  用于高碱性pH区域的基于香豆素的新型pH敏感荧光探针

  摘要：

  报告了新型可聚合香豆素基pH指示剂的设计，合成和光谱性质。它们显示出在高碱性pH范围内对pH的荧光响应，计算出的p K a值在12.2–12.5范围内。将指示剂共价固定在聚合物载体上可提供具有出色光稳定性的新型pH敏感材料。该材料对相似范围内的pH敏感，可应用于光学pH传感器中，以测量各种碱性介质中的pH。

  DOI：

  10.1016/j.dyepig.2020.108312
• 作为产物：
  描述：

  3-氨基苯酚 在 硫酸 作用下， 以 乙酸乙酯 为溶剂， 反应 19.5h， 生成 (4-氯甲基)香豆素-7-氨基甲酸乙酯
  参考文献：
  名称：

  用于高碱性pH区域的基于香豆素的新型pH敏感荧光探针

  摘要：

  报告了新型可聚合香豆素基pH指示剂的设计，合成和光谱性质。它们显示出在高碱性pH范围内对pH的荧光响应，计算出的p K a值在12.2–12.5范围内。将指示剂共价固定在聚合物载体上可提供具有出色光稳定性的新型pH敏感材料。该材料对相似范围内的pH敏感，可应用于光学pH传感器中，以测量各种碱性介质中的pH。

  DOI：

  10.1016/j.dyepig.2020.108312

文献信息

• Design, Synthesis, and Biological Evaluation of Imidazolyl Derivatives of 4,7-Disubstituted Coumarins as Aromatase Inhibitors Selective over 17-α-Hydroxylase/C17−20 Lyase
  作者：Angela Stefanachi、Angelo D. Favia、Orazio Nicolotti、Francesco Leonetti、Leonardo Pisani、Marco Catto、Christina Zimmer、Rolf W. Hartmann、Angelo Carotti

  DOI：10.1021/jm101120u

  日期：2011.3.24

  The design, synthesis, and biological evaluation of a series of new aromatase (AR, CYP19) inhibitors bearing an imidazole ring linked to a 7-substituted coumarin scaffold at position 4 (or 3) are reported. Many compounds exhibited an aromatase inhibitory potency in the nanomolar range along with a high selectivity over 17-α-hydroxylase/C17−20 lyase (CYP17). The most potent AR inhibitor was the 7-(3

  报道了一系列新的芳香酶（AR，CYP19）抑制剂的设计，合成和生物学评估，这些抑制剂带有与7位取代的香豆素骨架连接的4位（或3位）咪唑环。许多化合物在纳摩尔浓度范围内均显示出芳香化酶抑制潜能，并且对17-α-羟化酶/ C17-20裂解酶（CYP17）具有较高的选择性。最有效的AR抑制剂是7-（3,4-二氟苯氧基）-4-咪唑基甲基香豆素24，IC 50 = 47 nM。在一定数量的香豆素衍生物上的对接模拟可以识别驱动结合的最重要的相互作用，并清楚地表明香豆素和紧密相关的杂环分子支架的适当结构修饰的允许和不允许的区域。
• Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity
  作者：Nazanin Nahrjou、Avik Ghosh、Marina Tanasova

  DOI：10.3390/ijms22105073

  日期：——

  Specific link between high fructose uptake and cancer development and progression highlighted fructose transporters as potential means to achieve GLUT-mediated discrimination between normal and cancer cells. The gained expression of fructose-specific transporter GLUT5 in various cancers offers a possibility for developing cancer-specific imaging and bioactive agents. Herein, we explore the feasibility of delivering a bioactive agent through cancer-relevant fructose-specific transporter GLUT5. We employed specific targeting of GLUT5 by 2,5-anhydro-D-mannitol and investigated several drug conjugates for their ability to induce cancer-specific cytotoxicity. The proof-of-concept analysis was carried out for conjugates of chlorambucil (CLB) in GLUT5-positive breast cancer cells and normal breast cells. The cytotoxicity of conjugates was assessed over 24 h and 48 h, and significant dependence between cancer-selectivity and conjugate size was observed. The differences were found to relate to the loss of GLUT5-mediated uptake upon increased conjugate size and hydrophobicity. The findings provide information on the substrate tolerance of GLUT5 and highlight the importance of maintaining appropriate hydrophilicity for GLUT-mediated delivery.

  高果糖摄取与癌症发展和进展之间的特定联系突出了果糖转运蛋白作为区分正常细胞和癌细胞的一种潜在手段。在多种癌症中GLUT5的表达增加，为开发针对癌症的成像和生物活性剂提供了可能性。在此，我们探讨通过癌症相关的果糖特异性转运蛋白GLUT5传递生物活性剂的可行性。我们使用2,5-脱水-D-甘露醇特异性靶向GLUT5，并研究了几个药物共轭物诱导癌症特异性细胞毒性的能力。对CLB共轭物在GLUT5阳性的乳腺癌细胞和正常乳腺细胞中的概念验证分析进行了研究。在24小时和48小时内评估了共轭物的细胞毒性，并观察到癌症选择性与共轭物大小之间存在显著相关性。发现这些差异与共轭物大小和疏水性的增加导致GLUT5介导的摄取丧失有关。这些发现提供了关于GLUT5的底物耐受性的信息，并强调了保持适当亲水性对于GLUT介导的传递的重要性。
• Haloalkyl derivatives of reporter molecules used to analyze metabolic
  申请人：Molecular Probes, Inc.

  公开号：US05576424A1

  公开（公告）日：1996-11-19

  The subject invention provides substrates useful for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The substrates have the form XR-SPACER-REPORTER-BLOCK wherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate, -REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properties different from those of the substrate, -SPACER- is a covalent linkage, and XR- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z-S-H) to form a thioether conjugate (Z-S-R-). After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.

  该发明提供了用于分析细胞代谢活性的基质，通过改善仅在存在特定酶的完整细胞中保留可检测报告分子的能力。具体来说，改善的保留结果来自一个涉及将报告分子的卤代烷基衍生物与细胞内含半胱氨酸肽结合并解除报告分子的两部分过程。这些基质具有XR-SPACER-REPORTER-BLOCK的形式，其中-BLOCK是选择的可通过特定分析物作用去除的基团，以使REPORTER的光谱特性与基质不同，-REPORTER-是一种分子，当不再通过BLOCK-REPORTER键结合到BLOCK时，其光谱特性与基质不同，-SPACER-是一个共价连接，而XR-是一种卤代烷基基团，可以与细胞内巯基（Z-S-H）发生共价反应形成硫醚结合物（Z-S-R-）。在基质进入细胞后，分析物去除BLOCK，通过光谱特性的变化使REPORTER可检测，并且卤代烷基XR与细胞内巯基反应形成细胞内的硫醚结合物，这些结合物在细胞内得到良好保留。
• A macrocyclic coumarin-containing tripeptide via CuAAC chemistry
  作者：Sander S. van Berkel、Bas van der Lee、Floris L. van Delft、Floris P. J. T. Rutjes

  DOI：10.1039/b906762k

  日期：——

  A Cu-catalysed macrocyclisation was performed to obtain a macrocyclic coumarin-containing tripeptide for use in thrombin activity measurements.

  进行了一项铜催化的环化反应，以获得一种含有香豆素的环状三肽，用于凝血酶活性测定。
• Fluorescent haloalkyl derivatives of reporter molecules well retained in
  申请人：Molecular Probes, Inc.

  公开号：US05362628A1

  公开（公告）日：1994-11-08

  The subject invention provides a method for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The method for analyzing metabolic activity of cells involves the use of a substrate having the form XR-REPORTER-BLOCK wherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate, -REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properities different from those of the substrate, and XR-- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z--S--H) to form a thioether conjugate (Z--S--R--). After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.

  该发明提供了一种分析细胞代谢活性的方法，通过改善仅在存在特定酶的完整细胞中保留可检测报告分子的方法。具体而言，改善的保留结果来自一个涉及将报告分子的卤代烷基衍生物与细胞内含半胱氨酸肽结合并解除报告分子的两部分过程。分析细胞代谢活性的方法涉及使用具有XR-REPORTER-BLOCK形式的底物，其中-BLOCK是选择的可通过特定分析物作用去除的基团，以使REPORTER的光谱特性与底物不同，-REPORTER-是一种分子，当不再通过BLOCK-REPORTER键结合到BLOCK时，其光谱特性与底物不同，而XR--是一种卤代烷基基团，可以与细胞内巯基（Z--S--H）发生共价反应形成硫醚共轭物（Z--S--R--）。在底物进入细胞后，分析物去除BLOCK，通过光谱特性的变化使REPORTER可检测，并且卤代烷基XR与细胞内巯基反应形成细胞内的硫醚共轭物，这在细胞内得到良好保留。