Coumarins (2H-1-benzopyran-2-ones or 2H-chromen-2-ones) are important bicyclic heterocycles that constitute preferred scaffolds in medicinal chemistry. The coumarin unit is identified as a main fragment of important compounds with biological activities, including Novobiocin, Fraxin, Auraptene, and Osthol (Scheme 1). The coumarins play a significant role in plant physiology and biochemistry. They function as enzyme inhibitors, antioxidants, and precursors of toxic materials. They can be found in the actions of plant growth hormones and growth regulators, and are involved in both respiration and photosynthesis. They also function in the defense against different types of infections. Coumarins and their derivatives have been detected to demonstrate different types of biological and pharmacological activity such as anti-aggregating, antimicrobial, antioxidant, antibacterial, anti-inflammatory, anti-Alzheimer, anti-HIV, and anti-tumor properties, and have gained considerable attention because of their potential useful impacts on human health. From a synthetic standpoint, their reactions with nucleophiles offer novel ways to prepare new heterocyclic compounds. Synthetic coumarin derivatives have been achieved by chemical modification of the coumarin ring. Potentially, there are as many as six available sites of the basic molecule for reactions. Thus, a number of functionalized coumarins have been proposed as potent MAO and/or AChE inhibitors and some have been introduced for treating Alzheimer’s disease. The presence of amide functional groups will affect the biological activities of these compounds, as functions of the pattern of substitution in the coumarin ring. Aryl substituents on the coumarin skeleton change lipophilicity in crucial ways. Lipophilicity is an essential physicochemical parameter in the development of an antibacterial agent because it is closely related to the permeation of the agent through lipid layers in the cell wall of bacteria. The number of amide bonds and their position impact the kind and degree of biological activity. Accordingly, some new coumarin carboxamides were synthesized with effective anticoagulant activity, and with inhibition against BACE1, hMAO, acetylcholinesterase, and tumorogenesis. In continuation of our own work to design novel multicomponent reactions for the synthesis of furopyrimidine and coumarin-3-carboxamide compounds, we wish herein to report an approach to the synthesis of some new bisdiamidated coumarins

中文翻译：

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含有亲脂性间隔物的新型 bisChroman-3, 4-dicarboxamides 的一锅法合成

香豆素（2H-1-benzopyran-2-ones 或 2H-chromen-2-ones）是重要的双环杂环，构成药物化学中的首选支架。香豆素单元被鉴定为具有生物活性的重要化合物的主要片段，包括新生霉素、Fraxin、Auraptene 和 Osthol（方案 1）。香豆素在植物生理学和生物化学中起重要作用。它们起到酶抑制剂、抗氧化剂和有毒物质前体的作用。它们存在于植物生长激素和生长调节剂的作用中，并参与呼吸和光合作用。它们还可以防御不同类型的感染。已检测到香豆素及其衍生物具有不同类型的生物和药理活性，例如抗聚集、抗微生物、抗氧化、抗菌、抗炎、抗阿尔茨海默病、抗 HIV 和抗肿瘤特性，并因其对人类健康的潜在有益影响而受到广泛关注。从合成的角度来看，它们与亲核试剂的反应提供了制备新杂环化合物的新方法。合成香豆素衍生物已通过香豆素环的化学修饰获得。潜在地，基本分子有多达六个可用位点进行反应。因此，许多功能化香豆素已被提议作为有效的 MAO 和/或 AChE 抑制剂，并且一些已被引入用于治疗阿尔茨海默病。作为香豆素环中取代模式的函数，酰胺官能团的存在将影响这些化合物的生物活性。香豆素骨架上的芳基取代基以关键方式改变亲脂性。亲脂性是抗菌剂开发过程中必不可少的物理化学参数，因为它与抗菌剂通过细菌细胞壁脂质层的渗透密切相关。酰胺键的数量及其位置影响生物活性的种类和程度。因此，合成了一些具有有效抗凝活性并抑制 BACE1、hMAO、乙酰胆碱酯酶和肿瘤发生的新香豆素甲酰胺。为了继续我们自己的工作来设计用于合成呋喃嘧啶和香豆素-3-甲酰胺化合物的新型多组分反应，我们希望在此报告一种合成一些新的双二酰胺化香豆素的方法