3,4-dimethyl-7-aminocoumarin | 92287-81-5

• 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
• 英文名称: 3,4-dimethyl-7-aminocoumarin
• 英文别名: 7-amino-3,4-dimethylcoumarin；7-Amino-3,4-dimethyl-2H-chromen-2-one；7-amino-3,4-dimethylchromen-2-one
• CAS: 92287-81-5
• 化学式: C₁₁H₁₁NO₂
• 分子量: 189.214
• InChiKey: YWHWZGYRIVQPAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-dimethyl-7-aminocoumarin 在 盐酸 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 8.0h， 生成 3,4-dimethyl-7-((4-((10S)-dihydroartemisin-10-oxy)-methyl)-1H-1,2,3-triazol-1-yl)-2H-1-chromen-2-one
  参考文献：
  名称：

  Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents

  摘要：

  To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G(0)/G(1) phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.04.005
• 作为产物：
  描述：

  (3-羟基-苯基)-氨基甲酸乙酯 在 硫酸 、 溶剂黄146 作用下， 生成 3,4-dimethyl-7-aminocoumarin
  参考文献：
  名称：

  Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents

  摘要：

  To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G(0)/G(1) phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.04.005

文献信息

• Metal–coumarin complexes: synthesis and characterization of 7-isocyanocoumarin ligands and Mo(CO)4(7-isocyanocoumarin)2 complexes. X-ray crystal structure of Mo(CO)4(7-isocyano-4-trifluoromethylcoumarin)2
  作者：Daniel A. Freedman、Ivan Keresztes、Ann L. Asbury

  DOI：10.1016/s0022-328x(01)01186-x

  日期：2002.1

  The preparation and characterization of four different 7-isocyanocoumarin ligands is described. The four ligands are 3,4-dimethyl-7-isocyanocoumarin (Dmic), 7-isocyano-4-methylcoumarin (Mic), 3-chloro-7-isocyano-4-methylcoumarin (Cmic) and 7-isocyano-4-trifluoromethylcoumarin (Tic). Reaction of the four 7-isocyanocoumarin ligands with Mo(CO)4(pip)2 (pip=piperidine) gave the Mo(CO)4L2 complexes. IR and

  描述了四种不同的7-异氰基香豆素配体的制备和表征。四个配体是3,4-二甲基-7-异氰基香豆素（Dmic），7-异氰基-4-甲基香豆素（Mic），3-氯-7-异氰基-4-甲基香豆素（Cmic）和7-异氰基-4-三氟甲基香豆素（井字）。四个7-异氰基香豆素配体与Mo（CO）4（pip）2（pip =哌啶）的反应得到Mo（CO）4 L 2络合物。配合物的IR和UV-vis光谱表明，7-异氰基香豆素配体比简单的芳族异氰化物配体具有更强的π-酸。四个Mo（CO）4 L的UV-vis光谱中存在一个很强的可见光吸收带，该吸收带分配给金属到配体的电荷转移（MLCT）跃迁。2个复合体。在室温下，在二氯甲烷溶液中，对Mic，Cmic和Dmic复合物的MLCT带进行激发，产生橙黄色发射。Mo（CO）4（Mic）2与P（Ph）3在THF溶液中光解产生Mo（CO）3（PPh 3）（Mic）2。
• Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus
  作者：Xun-Cai Yang、Chun-Mei Zeng、Srinivasa Rao Avula、Xin-Mei Peng、Rong-Xia Geng、Cheng-He Zhou

  DOI：10.1016/j.ejmech.2022.114891

  日期：2023.1

  aminophosphonates as new antibacterial agents were designed and synthesized to combat severely bacterial resistance. Bioactivity assessment identified that 3-hydroxylphenyl aminophosphonate 6f with low hemolytic activity not only exhibited excellent inhibition potency against Staphylococcus aureus at low concentration (0.5 μg/mL) in vitro but also showed considerable antibacterial potency in vivo. Meanwhile

  设计并合成了独特的香豆素氨基膦酸盐作为新型抗菌剂，以对抗严重的细菌耐药性。生物活性评估表明，具有低溶血活性的 3-羟基苯基氨基膦酸酯6f不仅在低浓度（0.5 μg/mL）体外对金黄色葡萄球菌表现出优异的抑制效力，而且在体内也表现出相当大的抗菌效力。同时，活性化合物6f能够根除金黄色葡萄球菌生物膜，从而减轻金黄色葡萄球菌耐药性的发展。此外，化合物6f的药物组合与诺氟沙星合用可增强抗菌效果。机理探索表明分子6f能够破坏细胞膜的完整性，导致蛋白质渗漏和代谢抑制。细胞氧化还原稳态通过诱导活性氧 (ROS) 和活性氮 (RNS) 的产生而受到干扰，导致谷胱甘肽 (GSH) 活性降低和脂质过氧化。此外，化合物6f可以嵌入 DNA 碱基对中，从而阻碍正常的生物学功能。上述结果为进一步开发香豆素氨基膦酸盐作为抗菌剂提供了有力的信息。
• Novel Coumarin 7-Carboxamide/Sulfonamide Derivatives as Potential Fungicidal Agents: Design, Synthesis, and Biological Evaluation
  作者：Shu-Guang Zhang、Yu-Qiang Wan、Ya Wen、Wei-Hua Zhang

  DOI：10.3390/molecules27206904

  日期：——

  compounds have been used as fungicides for half a century, and dozens of varieties have been developed so far. This study focused on the introduction of carboxamide and sulfonamide moieties in a coumarin core to discover novel derivatives. Based on this strategy, we synthesized two series of novel carboxamide and sulfonamide substituted coumarin derivatives, and their fungicidal activity was also investigated

  香豆素类化合物具有抗肿瘤、抗凝血、抗HIV、抗真菌、杀虫等多种生物活性。酰胺类和磺胺类化合物作为杀菌剂已有半个世纪的历史，迄今已开发出几十个品种。这项研究的重点是在香豆素核心中引入羧酰胺和磺酰胺部分，以发现新的衍生物。基于此策略，我们合成了两个系列的新型羧酰胺和磺酰胺取代香豆素衍生物，并对其杀菌活性进行了研究。一些设计的化合物在初步试验中具有针对六种植物病原真菌的潜在活性，化合物6r突出显示。化合物6r表现出更强的杀真菌活性Botrytis cinerea (EC 50 = 20.52 µg/mL) 将成为进一步研究的主要结构。
• Structural Insights into Monoamine Oxidase Inhibitory Potency and Selectivity of 7-Substituted Coumarins from Ligand- and Target-Based Approaches
  作者：Marco Catto、Orazio Nicolotti、Francesco Leonetti、Andrea Carotti、Angelo Danilo Favia、Ramón Soto-Otero、Estefanía Méndez-Álvarez、Angelo Carotti

  DOI：10.1021/jm060183l

  日期：2006.8.1

  A new series of 3-, 4-, 7-polysubstituted coumarins have been designed and evaluated for their monoamine oxidase A and monoamine oxidase B (MAO-A and MAO-B) inhibitory potency. Substituents at position 7 consisted of a bridge of different physicochemical nature linking a phenyl ring to the coumarin scaffold. Structure-affinity and structure-selectivity relationships, derived through CoMFA-GOLPE and docking studies, revealed the key physicochemical interactions responsible for the observed MAO-B and MAO-A inhibitory potency and suggested the main structural determinants for high selectivity toward one of the two enzymatic isoforms. The predictive power of our models was proved with the design of a new inhibitor demonstrating an outstanding MAO-B affinity (pIC(50) = 8.29) and the highest MAO-B selectivity (Delta pIC(50) = 3.39) within the entire series of ligands examined herein.
• Inhibition of Monoamine Oxidases by Functionalized Coumarin Derivatives:  Biological Activities, QSARs, and 3D-QSARs
  作者：Carmela Gnerre、Marco Catto、Francesco Leonetti、Peter Weber、Pierre-Alain Carrupt、Cosimo Altomare、Angelo Carotti、Bernard Testa

  DOI：10.1021/jm001028o

  日期：2000.12.1

  A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC50 values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3,4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC50 value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2) = 0.72, r(2) = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.