6-methyl-3-(4′-nitrophenyl)coumarin | 74981-12-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 6-methyl-3-(4′-nitrophenyl)coumarin
• 英文别名: 6-Methyl-3-(4-nitrophenyl)chromen-2-one；6-methyl-3-(4-nitrophenyl)chromen-2-one
• CAS: 74981-12-7
• 化学式: C₁₆H₁₁NO₄
• 分子量: 281.268
• InChiKey: XGJDMHWEDXLYCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methyl-3-(4′-nitrophenyl)coumarin 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以97%的产率得到3-(4-aminophenyl)-6-methylcoumarin
  参考文献：
  名称：

  Potent and selective MAO-B inhibitory activity: Amino- versus nitro-3-arylcoumarin derivatives

  摘要：

  In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6 nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.001
• 作为产物：
  描述：

  对硝基苯乙酸 、 5-甲基水杨醛 在 乙酸酐 、 sodium hydride 作用下， 以 mineral oil 为溶剂， 反应 20.0h， 以80%的产率得到6-methyl-3-(4′-nitrophenyl)coumarin
  参考文献：
  名称：

  Synthesis and adenosine receptors binding affinities of a series of 3-arylcoumarins

  摘要：

  摘要：在这份研究中，我们报告了一系列选定的3-芳基香豆素化合物（化合物1-9）的合成、药理评价、吸收、分布、代谢和排泄性质的理论评价以及构效关系研究。我们对合成的化合物1-9进行了腺苷受体（ARs）结合活性和选择性评估。在评估的骨架的苯环中引入了不同的取代基，分别位于6位和3'或4'位置。对3-芳基香豆素骨架缺乏数据促使我们探索一系列衍生物的ARs结合活性。 方法：合成了一系列新的香豆素化合物（化合物1-9），并通过放射配体结合研究评估其对ARs的结合。 主要发现：分析实验数据，可以观察到简单的3-芳基香豆素和4'-硝基衍生物对评估的受体没有可检测的结合亲和力，尽管大多数其他取代衍生物具有良好的结合亲和力特性，特别是对hA1/hA3或仅hA3 AR。 结论：最显著的衍生物是化合物2，对hA3 AR具有最佳亲和力（Ki = 2680 nM），并对这个亚型具有显著的选择性。

  DOI：

  10.1111/jphp.12135

文献信息

• Synthesis and Structure-Activity Relationships of Novel Amino/Nitro Substituted 3-Arylcoumarins as Antibacterial Agents
  作者：Maria Matos、Saleta Vazquez-Rodriguez、Lourdes Santana、Eugenio Uriarte、Cristina Fuentes-Edfuf、Ysabel Santos、Angeles Muñoz-Crego

  DOI：10.3390/molecules18021394

  日期：——

  A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin). The preliminary structure-activity relationship (SAR) study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported.

  我们合成了一系列新的氨基/硝基取代的 3-芳基香豆素，并评估了它们对临床分离的金黄色葡萄球菌（革兰氏阳性）和大肠杆菌（革兰氏阴性）的抗菌活性。其中一些分子对金黄色葡萄球菌的抗菌活性与所用标准（草酸和氨苄西林）相当。初步的结构-活性关系（SAR）研究表明，对金黄色葡萄球菌的抗菌活性取决于 3-芳基香豆素取代模式的位置。为了寻找抗菌活性和选择性的结构特征，本手稿报告了 3-芳基香豆素支架上硝基、甲基、甲氧基、氨基和溴取代基的不同位置。
• Potent and selective MAO-B inhibitory activity: Amino- versus nitro-3-arylcoumarin derivatives
  作者：Maria João Matos、Fernanda Rodríguez-Enríquez、Santiago Vilar、Lourdes Santana、Eugenio Uriarte、George Hripcsak、Martín Estrada、María Isabel Rodríguez-Franco、Dolores Viña

  DOI：10.1016/j.bmcl.2014.12.001

  日期：2015.2

  In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6 nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis and adenosine receptors binding affinities of a series of 3-arylcoumarins
  作者：Maria João Matos、Veronika Hogger、Alexandra Gaspar、Sonja Kachler、Fernanda Borges、Eugenio Uriarte、Lourdes Santana、Karl-Norbert Klotz

  DOI：10.1111/jphp.12135

  日期：2013.10.14

  In the present communication, we report the synthesis, pharmacological evaluation, theoretical evaluation of absorption, distribution, metabolism and excretion properties and structure–activity relationship study of a selected series of 3-arylcoumarins (compounds 1–9). Adenosine receptors (ARs) binding activity and selectivity of the synthesized compounds 1–9 were evaluated in this study. Different substituents were introduced in both benzene rings of the evaluated scaffold, at positions 6 and 3′ or 4′ of the moiety. The lack of data on the 3-arylcoumarin scaffold encouraged us to explore the ARs' binding activity of a selected series of derivatives.

  A new series of coumarins (compounds 1–9) were synthesized and evaluated by radioligand binding studies towards ARs.

  Analysing the experimental data, it can be observed that neither the simple 3-arylcoumarin nor the 4′-nitro derivatives presented detectable binding affinity for the evaluated receptors, although most of the other substituted derivatives have good binding affinity profiles, especially against the hA1/hA3 or only hA3 AR.

  The most remarkable derivative is compound 2, presenting the best affinity for hA3 AR (Ki = 2680 nM) and significant selectivity for this subtype.

  摘要：在这份研究中，我们报告了一系列选定的3-芳基香豆素化合物（化合物1-9）的合成、药理评价、吸收、分布、代谢和排泄性质的理论评价以及构效关系研究。我们对合成的化合物1-9进行了腺苷受体（ARs）结合活性和选择性评估。在评估的骨架的苯环中引入了不同的取代基，分别位于6位和3'或4'位置。对3-芳基香豆素骨架缺乏数据促使我们探索一系列衍生物的ARs结合活性。 方法：合成了一系列新的香豆素化合物（化合物1-9），并通过放射配体结合研究评估其对ARs的结合。 主要发现：分析实验数据，可以观察到简单的3-芳基香豆素和4'-硝基衍生物对评估的受体没有可检测的结合亲和力，尽管大多数其他取代衍生物具有良好的结合亲和力特性，特别是对hA1/hA3或仅hA3 AR。 结论：最显著的衍生物是化合物2，对hA3 AR具有最佳亲和力（Ki = 2680 nM），并对这个亚型具有显著的选择性。