ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate | 54396-24-6

• 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: ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate
• 英文别名: 3-ethoxycarbonyl-6-methylcoumarin；ethyl 6-methylcoumarin-3-carboxylate；ethyl 6-methyl-2-oxochromene-3-carboxylate
• CAS: 54396-24-6
• 化学式: C₁₃H₁₂O₄
• 分子量: 232.236
• InChiKey: KSWKCZHIAJEFGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate 在 盐酸 、 氯化亚砜 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 6-methyl-2-oxo-2H-1-benzopyran-3-carboxylic acid chloride
  参考文献：
  名称：

  3,6-Disubstituted Coumarins as Mechanism-Based Inhibitors of Thrombin and Factor Xa

  摘要：

  In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two of the most promising targets for the development of anticoagulant drugs. This allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester in the 3-position and a chloromethyl moiety in the 6-position, as a very potent THR inhibitor (k(i)/K-I, = 37 000 M-1 s(-1)). Moreover, this compound exhibits good selectivity over FXa (168-fold) and trypsin (54-fold). The mechanism of inactivation was investigated in this series and significantly differs from that previously observed with (x-chymotrypsin. Indeed, the addition of hydrazine on the THR-inhibitor complex promotes a partial induced THR reactivation. This reactivation, confirmed by LC/MS, showed the resurgence of the native THR and a new dihydrazide complex. Docking experiments were then efficiently used to explain the trends observed in the enzymatic assays as well as to corroborate the postulated inhibition mechanism. Finally, the cell permeability of our derivatives was estimated using a computational approach.

  DOI：

  10.1021/jm050448g
• 作为产物：
  描述：

  2-羟基-5-(羟基甲基)苯甲醛 在 哌啶 、 吡啶 、 palladium on activated charcoal 、 乙醇 作用下， 生成 ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate
  参考文献：
  名称：

  Über den 2-Oxy-5-chlormethyl-benzaldehyd und den 2-Methoxy-5-chlormethyl-benzaldehyd.

  摘要：

  DOI：

  10.1002/ardp.19422800404

文献信息

• Synthesis of coumarin-3-carboxylic esters via FeCl3-catalyzed multicomponent reaction of salicylaldehydes, Meldrum's acid and alcohols
  作者：Xinwei He、Yongjia Shang、Yao Zhou、Zhiyu Yu、Guang Han、Wenjing Jin、Jiaojiao Chen

  DOI：10.1016/j.tet.2014.12.042

  日期：2015.2

  FeCl3-catalyzed multicomponent reaction was developed for the facile synthesis of coumarin-3-carboxylic ester derivatives in a highly atom-economic and environmentally friendly way. Using simple and cheaply available salicylaldehydes, Meldrum's acid and alcohols as the starting materials, the method needs no extra additives and features wide substrate scope, good functional group tolerance and mild reaction conditions

  开发了FeCl 3催化的多组分反应，以高度原子经济和环境友好的方式容易地合成香豆素-3-羧酸酯衍生物。该方法使用简单廉价的水杨醛，Meldrum的酸和醇作为起始原料，不需要额外的添加剂，并且具有广泛的底物范围，良好的官能团耐受性和温和的反应条件。
• Coumarins and adenosine receptors: New perceptions in structure-affinity relationships
  作者：André Fonseca、Maria João Matos、Santiago Vilar、Sonja Kachler、Karl-Norbert Klotz、Eugenio Uriarte、Fernanda Borges

  DOI：10.1111/cbdd.13075

  日期：2018.1

  Adenosine receptor (AR) subtypes are involved in several physiological and pharmacological processes. Ligands that are able to selectively modulate one receptor subtype can delay or slow down the progression of diverse diseases. In this context, our research group focused its investigation into the discovery and development of novel, potent and selective AR ligands based on coumarin scaffold. Therefore

  腺苷受体（AR）亚型涉及几种生理和药理过程。能够选择性调节一种受体亚型的配体可以延缓或减缓多种疾病的发展。在这种情况下，我们的研究小组将研究重点放在了基于香豆素骨架的新型，有效和选择性AR配体的发现和开发上。因此，一系列的3-phenylcarboxamidocoumarins合成以及它们在人AR亚型的亲和性是通过放射性配体结合测定法用于筛选阿1，A 2A和A 3个受体和对于A 2B由腺苷酸环化酶测定。发现化合物26最显着，其h A1 / ħ甲3和ħ甲2A / ħ甲3选择性的42，为A 3 AR（ķ我 = 2.4μ米）。受体驱动的分子建模研究为化合物26的结合/选择性数据以及随后的优化过程提供了有价值的信息。此外，化合物26根据与该概念有关的一般指导原则表现出药物样性质。
• Sonochemistry as a General Procedure for the Synthesis of Coumarins­, Including Multigram Synthesis
  作者：Ligia da Silveira Pinto、Marcus de Souza

  DOI：10.1055/s-0036-1590201

  日期：2017.6

  the compounds obtained using the classical procedures. This study describes a general procedure for the synthesis of different coumarins via sonochemistry using active methylene compounds and 2-hydroxybenzaldehydes or resorcinol. The application of sonochemistry for the synthesis of these compounds was also very effective on a multigram scale with a higher yield, higher amount of crystalline compound

  摘要 这项研究描述了使用活性亚甲基化合物和2-羟基苯甲醛或间苯二酚通过声化学合成不同香豆素的一般程序。与用经典方法获得的化合物相比，声化学在合成这些化合物上的应用在多克规模上也非常有效，具有更高的产率，更高的结晶化合物的量以及更短的反应时间。 这项研究描述了使用活性亚甲基化合物和2-羟基苯甲醛或间苯二酚通过声化学合成不同香豆素的一般程序。与用经典方法获得的化合物相比，声化学在合成这些化合物上的应用在多克规模上也非常有效，具有更高的产率，更高的结晶化合物的量以及更短的反应时间。
• Synthesis and antioxidant activity of conjugates of hydroxytyrosol and coumarin
  作者：Wen-Bo Li、Xue-Peng Qiao、Zi-Xiao Wang、Shuai Wang、Shi-Wu Chen

  DOI：10.1016/j.bioorg.2020.104427

  日期：2020.12

  Antioxidants have been the subject of intense research interest due to their numerous health benefits. In this work, a series of new conjugates of hydroxytyrosol and coumarin were synthesized and evaluated for their free radical scavenging, toxicity and antioxidant mechanism in vitro. The all target compounds 14a–t exhibited better radical scavenging activity than BHT, hydroxytyrosol, and coumarin

  抗氧化剂由于其许多健康益处而已成为人们广泛研究的主题。在这项工作中，合成了一系列新型的羟基酪醇和香豆素共轭物，并对其体外自由基清除，毒性和抗氧化机理进行了评估。在DPPH自由基和ABTS +自由基阳离子清除试验中，所有目标化合物14a–t均表现出比BHT，羟基酪醇和香豆素更好的自由基清除活性。结构-活性关系研究表明，香豆素环上羟基的数量和位置对于良好的抗氧化能力至关重要。此外，最有前途的化合物14q在正常的WI-38和GES细胞中，溶血试验显示的毒性比BHT弱，抗增殖作用较弱，并且H 2 O 2诱导的HepG2细胞活力增强。另外，14q降低了HepG2细胞的凋亡百分比，减少了ROS的产生和LDH的释放，并改善了H 2 O 2处理的HepG2细胞中的GSH和SOD水平。最后，在甲醇溶液中，14q比羟基酪醇具有更高的稳定性。这些结果表明，羟基酪醇和香豆素的结合物显示出更好的抗氧化能力，并且是发现新型潜在抗氧化剂的有效方法。
• Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: a facile approach for the synthesis of substituted 2H-chromene-3-carboxylates
  作者：Mudulkar Sairam、Gannerla Saidachary、Bhimapaka China Raju

  DOI：10.1016/j.tetlet.2015.01.114

  日期：2015.3

  A highly efficient and simple protocol has been developed for the preparation of ethyl 2-oxo-2H-chromene-3-carboxylates 3a–v by the condensation of salicylaldehydes 1a–v with ethyl 4,4,4-trichloro-3-oxobutanoate 2 for the first time. The reaction is proceeding via Knoevenagel pathway followed by a selective addition of the phenolic hydroxyl group to the carbonyl group adjacent to the CCl3 group rather

  通过将水杨醛1a - v与4,4,4-三氯-3-氧代丁酸乙酯缩合，已开发出一种高效且简单的方案，用于制备2-oxo-2 H-色烯-3-羧酸乙酯3a – v第一次2。该反应通过Knoevenagel途径进行，随后由于强的电子吸收作用，将酚羟基选择性地添加到与CCl 3基团相邻的羰基上而不是酯羰基上，并且生成了香豆素衍生物3a，消除了CHCl 3。