N-(3,4-dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide | 1053228-86-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,4-dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide
• 英文别名: 2-(3,4-dimethoxyphenylaminocarbonyl)chromone；N-(3,4-dimethoxyphenyl)-4-oxochromene-2-carboxamide
• CAS: 1053228-86-6
• 化学式: C₁₈H₁₅NO₅
• 分子量: 325.321
• InChiKey: PEEXKGYECCQJHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  色酮-2-甲酸 在 五氯化磷 、 三乙胺 作用下， 以 二氯甲烷 、 环己烷 为溶剂， 反应 14.0h， 生成 N-(3,4-dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide
  参考文献：
  名称：

  作为新型抗生物膜剂的铜绿假单胞菌群体感应信号直接和逆向 Chromone-2-Carboxamides 类似物的研究

  摘要：

  生物膜形成被认为是治疗失败的主要原因，因为生物膜中的细菌对抗菌剂具有更高的保护作用。因此，生物膜相关感染的治疗极具挑战性，对公众健康构成重大关注，并带来巨大的经济影响。铜绿假单胞菌特别是，它是一种“关键优先”病原体，负责严重感染，特别是在囊性纤维化患者中，因为它具有形成耐药生物膜的能力。因此，需要新的治疗方法来完成提供新靶点和作用模式的分子管道。生物膜的形成主要受群体感应 (Quorum Sensing, QS) 控制，这是一种基于信号分子的通讯系统。在本研究中，我们采用分子对接方法 (Autodock Vina) 来评估两个系列的基于色酮的化合物作为 PqsR（一种 LuxR 型受体）的可能配体。大多数化合物对 PqsR 显示出良好的预测亲和力，高于 PQS 天然配体。受到这些对接结果的鼓舞，我们使用两条优化路线合成了一个包含 34 种直接和 25 种逆色酮甲酰胺的文库，以 2-色酮羧酸

  DOI：

  10.3390/ph15040417

文献信息

• Chromone, a Privileged Scaffold for the Development of Monoamine Oxidase Inhibitors
  作者：Alexandra Gaspar、Tiago Silva、Matilde Yáñez、Dolores Vina、Franscisco Orallo、Francesco Ortuso、Eugenio Uriarte、Stefano Alcaro、Fernanda Borges

  DOI：10.1021/jm2004267

  日期：2011.7.28

  Two series of novel chromone derivatives were synthesized and investigated for their ability to inhibit the activity of monoamine oxidase. The SAR data indicate that chromone derivatives with substituents in position 3 of γ-pyrone nucleus act preferably as MAO-B inhibitors, with IC50 values in the nanomolar to micromolar range. Almost all chromone 3-carboxamides display selectivity toward MAO-B. Identical

  合成了两种新的色酮衍生物，并研究了它们抑制单胺氧化酶活性的能力。SAR数据表明，在γ-吡喃酮核的3位具有取代基的色酮衍生物优选用作MAO-B抑制剂，IC 50值在纳摩尔至微摩尔范围内。几乎所有色酮3-羧酰胺均显示出对MAO-B的选择性。上在两种同种型（色酮类的活性完全丧失的γ吡喃酮核结果2位置是相同的取代2 - 12除了3和5）。显色酮（19）表现出MAO-B IC 50具有63 nM的选择性，是MAO-A的1000倍以上，并且具有拟可逆性抑制剂的作用。对接活性最高的化合物的MAO结合的实验突出显示了同工型A和B之间的不同相互作用方式。色酮异构体之间的溶剂化作用的差异分析提供了有关3取代色酮衍生物优越轮廓的更多见解。
• Discovery of novel A3 adenosine receptor ligands based on chromone scaffold
  作者：Alexandra Gaspar、Joana Reis、Sonja Kachler、Silvia Paoletta、Eugenio Uriarte、Karl-Norbert Klotz、Stefano Moro、Fernanda Borges

  DOI：10.1016/j.bcp.2012.03.007

  日期：2012.7

  has been developed. Accordingly, two series of novel chromone carboxamides placed at positions C2 (compounds 2-13) and C3 (compounds 15-26) of the gamma-pyrone ring were synthesized using chromone carboxylic acids (compounds 1 or 14) as starting materials. From this study and on the basis of the obtained structure-activity relationships it was concluded that the chromone carboxamide scaffold represent

  已经开发了一个致力于发现新化学实体（NCE）作为AR配体的项目，该配体包含苯并-γ-吡喃酮[（4H）-1-苯并吡喃-4-酮]子结构。因此，使用色酮羧酸（化合物1或14）作为起始原料，合成了位于γ-吡喃酮环的位置C2（化合物2-13）和C3（化合物15-26）的两个新的色酮羧酰胺系列。从这项研究中，并在获得的结构-活性关系的基础上，得出的结论是，色酮羧酰胺支架代表了一类新型的AR配体。最显着的色酮是对A3AR表现出更好亲和力的化合物21和26（分别为Ki = 3680 nM和Ki = 3750 nM）。受体驱动的分子建模研究提供了有关色酮的结合/选择性数据的信息。
• In search for new chemical entities as adenosine receptor ligands: Development of agents based on benzo-γ-pyrone skeleton
  作者：Alexandra Gaspar、Joana Reis、Maria João Matos、Eugenio Uriarte、Fernanda Borges

  DOI：10.1016/j.ejmech.2012.05.033

  日期：2012.8

  A selected series of chromone carboxamides synthesized in our laboratory were evaluated by radioligand binding studies towards adenosine receptors. All the chromone-3-carboxamides (compounds 8-12) exhibit A(2B) receptor displacement percentage superior to 50%. The best results were obtained with phenolic substituents (compounds 9 and 12) in the position 3 of pyrone ring with a K-i value of 2890 and 1350 nM. In addition, the predicted ADME properties for the chromone carboxamides under study are in accordance with the general requirements for the drug discovery and development process and in turn they have potential to emerge as a drug candidate.In summary, N-phenylchromone-3-carboxamide may be proposed as a promising scaffold that can undergo optimization as a selective A(2B)AR antagonist given its lower affinity for A(1)AR and A(2A)AR. Accordingly, one can propose this new chromone class as a promising scaffold for tackling adenosine receptors, namely of A(2B) subtype. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Accelerating lead optimization of chromone carboxamide scaffold throughout microwave-assisted organic synthesis
  作者：Fernando Cagide、Joana Reis、Alexandra Gaspar、Fernanda Borges

  DOI：10.1016/j.tetlet.2011.09.095

  日期：2011.11

  Microwave irradiation offers a considerable advantage over conventional synthesis with rate enhancements and cleaner reactions. Accordingly, a new microwave-assisted method for the synthesis of functionalized chromones was developed allowing the obtention of a library of chromone carboxamides. The method has been shown to present several advantages including operational simplicity, good performance, significant reduction in reaction time, less formation of by-products, and easier work-up. (C) 2011 Elsevier Ltd. All rights reserved.
• [EN] CHROMONE DERIVATIVES FOR USE AS ANTIOXIDANTS/PRESERVATIVES<br/>[FR] DÉRIVÉS DE CHROMONE DESTINÉS À ÊTRE UTILISÉS COMME ANTI-OXYDANTS/CONSERVATEURS
  申请人：UNIV DO PORTO

  公开号：WO2008104925A1

  公开（公告）日：2008-09-04

  [EN] The current invention depicts the synthesis of new chromone amide derivatives placed at positions C2 and C3 of the chromone nucleus. The synthesised compounds possess the general formulas (I) and (II) as displayed below. This new compounds possessing different substitution patterns were obtained through a condensation reaction between 2- or 3 - carboxychromone and aniline (phenylamine) or its substituted derivatives in fairly good yields. The syntheses of the dihydroxylated compounds were performed by a demethylation reaction of the previously obtained monomethoxylated chromones. Some of these compounds possess a putative use as antioxidant/preservatives for pharmaceutical, cosmetic and/or food industries.
  [FR] La présente invention porte sur la synthèse de nouveaux dérivés de chromone amide placés dans les positions C2 et C3 du noyau chromone. Les composés synthétisés possèdent des formules générales A et B telles que présentées ci-après. Ces nouveaux composés possédant différents motifs de substitution ont été obtenus par une réaction de condensation entre la 2- ou 3-carboxychromone et l'aniline (phénylamine) ou ses dérivés substitués dans des rendements assez bons. Les synthèses des composés dihydroxylés ont été effectuées par une réaction de déméthylation des chromones monométhoxylées préalablement obtenues. Les industries pharmaceutiques, cosmétiques et/ou alimentaires utilisent quelques-uns de ces composés comme anti-oxydants/conservateurs présumés.