5,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid | 54880-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid
• 英文别名: 5,7-dimethoxy-4-oxochromene-2-carboxylic acid
• CAS: 54880-49-8
• 化学式: C₁₂H₁₀O₆
• 分子量: 250.208
• InChiKey: IZZCHPWOMVNENL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid 在 盐酸 、 三溴化硼 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-{10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-5-hydroxy-7-methoxy-4-oxo-4H-chromene-2-carboxamide hydrochloride
  参考文献：
  名称：

  New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

  摘要：

  By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a new family of tacrine-4-oxo-4H-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H-chromene was chosen for its radical capture and beta-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine-4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-{10-[(1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-4 H-chromene-2-carboxamide (19) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties.

  DOI：

  10.1021/jm201460y
• 作为产物：
  描述：

  2-羟基-4,6-二甲氧基苯乙酮 在 sodium ethanolate 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 14.25h， 生成 5,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid
  参考文献：
  名称：

  设计和合成含有黄酮或色酮部分作为基于P糖蛋白的多药耐药性（MDR）调节剂的氨基酯异二聚体

  摘要：

  在这项研究中，合成了一系列新的异二聚体。这些衍生物是Ñ，ñ -双（链烷醇）胺的芳基的酯或Ñ，ñ -带有甲氧基化的芳基残基与黄酮或色酮部分结合的双（乙氧基乙醇）胺芳基酯。研究了这些新化合物，以评估其对多药耐药性白血病细胞系的P-gp调节活性。一些新化合物显示出良好的MDR逆转活性。有趣的是，该系列新化合物不符合先前合成的带有不同芳族部分的类似物所概述的结构-活性关系（SAR）。对于本文所述的化合物，活性与不同的特征相关，尤其是垫片的特征，这对于与泵的相互作用似乎至关重要。这一事实表明，黄酮或色酮残基的存在会影响这些系列产品的SAR，而且柔性分子可以通过P-gp识别位点找到不同的生产性结合模式。这些结果支持了新化合物的合成，这可能是开发控制P-gp依赖性MDR的药物的有用线索。

  DOI：

  10.1016/j.bmc.2017.11.016

文献信息

• Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance
  作者：Maria Schwarz、Rebecca F. M. Eno、Stefanie Freitag-Pohl、Christopher R. Coxon、Hannah E. Straker、David J. Wortley、David J. Hughes、Glynn Mitchell、Jenny Moore、Ian Cummins、Nawaporn Onkokesung、Melissa Brazier-Hicks、Robert Edwards、Ehmke Pohl、Patrick G. Steel

  DOI：10.1039/d1ob01802g

  日期：——

  discovered a specific flavonoid as a natural ligand of the recombinant enzyme. A series of related synthetic flavonoids was prepared and their binding to AmGSTF1 was investigated showing a high affinity for derivatives bearing a O-5-decyl-α-carboxylate. Molecular modelling based on high-resolution crystal structures allowed a binding pose to be defined which explained flavonoid binding specificity.

  禾本科杂草多重除草剂抗性（MHR）的进化和增长继续威胁着全球谷物生产。虽然多种过程可能导致耐药性，但早期的工作已将 phi 类谷胱甘肽-S-转移酶 ( Am GSTF1) 确定为黑草 ( Alopecurus myosuroides ) 中 MHR 的功能性生物标志物。这项研究结合化学和结构生物学，进一步深入了解Am GSTF1 在 MHR 中的作用。获得了野生型Am GSTF1 的晶体结构，以及两个专门设计的变体，这些变体允许与Am GSTF1 抑制剂 4-氯-7-硝基-苯并呋喃 (NBD-Cl) 的谷胱甘肽和谷胱甘肽加合物进行共晶结构测定。这些研究表明NBD-Cl的抑制活性与活性位点的封闭和底物结合的阻碍有关。使用配体钓鱼实验寻找Am GSTF1 的其他选择性抑制剂，确定了许多黄酮类化合物作为潜在的配体。随后使用黑草提取物进行的实验发现了一种特定的黄酮类化合物作为重组酶的天然配体。制备
• New flavonoid – <i>N</i>,<i>N</i>-dibenzyl(<i>N</i>-methyl)amine hybrids: Multi-target-directed agents for Alzheimer´s disease endowed with neurogenic properties
  作者：Martín Estrada-Valencia、Clara Herrera-Arozamena、Concepción Pérez、Dolores Viña、José A. Morales-García、Ana Pérez-Castillo、Eva Ramos、Alejandro Romero、Erik Laurini、Sabrina Pricl、María Isabel Rodríguez-Franco

  DOI：10.1080/14756366.2019.1581184

  日期：2019.1.1

  pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)amine (DBMA) fragments, new CNS-permeable flavonoid - DBMA hybrids (1-13) were obtained. They were

  多靶标定向配体（MTDLs）的设计是获得有效的复杂病理学药物的有效方法。结合神经修复特性并阻断神经毒性级联反应第一步的MTDL可能是治疗神经退行性疾病（ND）的长期以来一直希望的补救措施。通过将两个具有众所周知的ND目标活性的特权支架，类黄酮和N，N-二苄基（N-甲基）胺（DBMA）片段连接起来，获得了新的CNS渗透性类黄酮-DBMA杂种（1-13）。 。他们在一系列涉及阿尔茨海默氏病（AD）和其他ND的靶标中进行了生物学评估，这些靶标分别是人胆碱酯酶（hAChE / hBuChE），β-分泌酶（hBACE-1），单胺氧化酶（hMAO-A / B），脂氧合酶5（hLOX-5）和sigMA受体（σ1R/σ2R）。经过漏斗式筛选后，6 7-二甲氧基色酮-DBMA（6）因其具有神经源性和在hAChE，hLOX-5，hBACE-1和σ1R中具有有趣的MTD谱而突出显示。分子动力学模拟显示杂种6最相
• Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups
  作者：Tao Xing、Shuyan Yu、Meng Qin、Mengdi Zhang、Yuheng Ma、Zhibin Xiao

  DOI：10.1016/j.bmcl.2023.129539

  日期：2023.11

  7 of the parent nucleus of the chromones can enhance the anti-inflammatory activity of the chromones. The molecular docking studies predicted the mode of interaction between the compounds and protein. Additionally, these studies have demonstrated that the amide bond is the key radical to the anti-inflammatory effect. Based on the summary of the aforementioned studies, it can be inferred that compound

  炎症是免疫系统对感染、损伤或刺激等各种刺激的最初生物反应。广泛的研究表明，越来越多的疾病是由炎症机制引发的。目前，抗炎药物因其治疗优势而广泛应用于临床。然而，我们也不能忽视潜在的副作用。本工作采用联合药物设计原理，设计合成了一系列以色酮为母核的酰胺类化合物。生物学评价结果表明，与阳性药物布洛芬相比，四种化合物表现出较低的EC 50值。值得注意的是，化合物5-9 对 RAW264.7 细胞中脂多糖 (LPS) 诱导的一氧化氮 (NO) 的产生表现出最佳的抑制活性 (EC 50 = 5.33 ± 0.57 μM)。构效关系(SAR)表明，色酮母核5位和8位吸电子基团或6位和7位给电子基团的存在可以增强色酮的抗炎活性。分子对接研究预测了化合物与蛋白质之间的相互作用模式。此外，这些研究表明酰胺键是抗炎作用的关键基团。根据上述研究的总结，可以推断化合物5-9具有作为抗炎药物的潜力，值得进一步研究。
• CHROMONE DERIVATIVES, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1211251A1

  公开（公告）日：2002-06-05

  The invention provides chromone derivatives of the following general formula, a process for preparing such chromone derivatives and a prophylactic and therapeutic agent comprising such chromone derivatives for bone diseases and chondropathy: wherein the ring A is an optionally substituted benzene ring; R1 is an optionally substituted non-aromatic heterocyclic group; R2 is a hydrogen atom or hydrocarbon group; R3 is a hydrogen atom, hydrocarbon group or halogen; n is an integer of 0-3; or a salt thereof.

  本发明提供了通式如下的铬酮衍生物、制备此类铬酮衍生物的工艺以及包含此类铬酮衍生物的用于骨病和软骨病的预防和治疗剂： 其中，环 A 是任选取代的苯环；R1 是任选取代的非芳香杂环基团；R2 是氢原子或烃基团；R3 是氢原子、烃基团或卤素；n 是 0-3 的整数；或其盐。
• Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization
  作者：José Esteban Obreque-Balboa、Qiu Sun、Günther Bernhardt、Burkhard König、Armin Buschauer

  DOI：10.1016/j.ejmech.2015.12.010

  日期：2016.2

  A series of chromones, bearing substituted amino groups or N-substituted carboxamide moieties in position 2, was synthesized and characterized in cellular assays for modulation of the ABC transporters ABCC1 (MDCKII-MRP1 cells), ABCB1 (Kb-V1 cells) and ABCG2 (MCF-7/Topo cells). The most potent ABCC1 modulators identified among these flavonoid-type compounds were comparable to the reference compound reversan regarding potency, but superior in terms of selectivity concerning ABCB1 and ABCG2 (2-[4-(Benzo[c][1,2,5]oxadiazol-5-ylmethyl)piperazin-1-yl]-5,7-dimethoxy-4H-chromen-4-one (51): ABCC1, IC50 11.3 mu M; inactive at ABCB1 and ABCG2). Compound 51 was as effective as reversan in reverting ABCC1-mediated resistance to cytostatics in MDCKII-MRP1 cells and proved to be stable in mouse plasma and cell culture medium. Modulators, such as compound 51, are of potential value as pharmacological tools for the investigation of the (patho)physiological role of ABCC1. (C) 2015 Elsevier Masson SAS. All rights reserved.