6-methoxy-4-oxo-4H-chromene-3-carboxylic acid | 51085-93-9

• 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: 6-methoxy-4-oxo-4H-chromene-3-carboxylic acid
• 英文别名: 6-methoxy-4-oxochromene-3-carboxylic acid
• CAS: 51085-93-9
• 化学式: C₁₁H₈O₅
• 分子量: 220.182
• InChiKey: CKKSTBSDUGEMOZ-UHFFFAOYSA-N

物化性质

• 熔点：
  173-174 °C(Solv: acetone (67-64-1))
• 沸点：
  396.8±42.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-methoxy-4-oxo-4H-chromene-3-carboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  3,3'-羰基双（色酮）的合成及其作为哺乳动物碱性磷酸酶抑制剂的活性†

  摘要：

  通过色酮-3-羧酸氯与3-（二甲基氨基）-1-（2-羟苯基）-反应，制备了迄今未知的3，3′-羰基-双（色酮）8，其是通过羰基桥接的二聚色酮。 2丁1酮9。该方法通常适用于发现抑制哺乳动物碱性磷酸酶的新型对称或非对称产物的合成。

  DOI：

  10.1039/c5ob01350j
• 作为产物：
  描述：

  2,5-二羟基苯乙酮 在 sodium chlorite 、 氨基磺酸 、 potassium carbonate 、 sodium iodide 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 6-methoxy-4-oxo-4H-chromene-3-carboxylic acid
  参考文献：
  名称：

  Structure−Activity Relationships of a Novel Class of Endothelin-A Receptor Antagonists and Discovery of Potent and Selective Receptor Antagonist, 2-(Benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2H-chromene-3- carboxylic Acid (S-1255). 1. Study on Structure−Activity Relationships and Basic Structure Crucial for ET_A Antagonism

  摘要：

  A novel series of endothelin-A (ETA) selective receptor antagonists having a 2H-chromene skeleton are described. A lead compound, 2-(benzo[1,3]dioxol-5-yl)-2H-chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin II antagonist. A structure-activity relationship (SAR) study of 3 reveals that the structural requirements essential for potent and selective ETA receptor binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy groups at the 2-, 3-, and 6-positions, respectively, on the (R)-2H-chromene skeleton. The substituent at the 4-position is also important for improving the activity, and various hydrophobic functional groups of 6-9 Angstrom such as liner, branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups, and even halogen atoms were acceptable. These results suggest that (R)-2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108, is the crucial basic structure to be recognized by the ETA receptor. The most potent compound is (R)-48 (S-1255), which binds to the ETA receptor with an IC50 value of 0.19 nM and is 630-fold selective for the ETA receptor than for the ETB receptor. This compound has 55% oral bioavailability in rats. On the basis of the SAR, the roles of each substituent in the receptor binding are discussed.

  DOI：

  10.1021/jm010382z

文献信息

• Antiproliferative chromone derivatives induce K562 cell death through endogenous and exogenous pathways
  作者：Runwei Jiao、Fanxing Xu、Xiaofang Huang、Haonan Li、Weiwei Liu、Hao Cao、Linghe Zang、Zhanlin Li、Huiming Hua、Dahong Li

  DOI：10.1080/14756366.2020.1740696

  日期：2020.1.1

  S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, 15a induced K562 cells death

  摘要 制备了一系列色酮的呋喃喃衍生物。测试了针对五种癌细胞系HepG2，MCF-7，HCT-116，B16和K562以及两种正常人细胞系L-02和PBMC的抗增殖活性。在它们之中，化合物15a表现出最有效的抗增殖活性。通过Griess分析还发现15a在45分钟的峰值时间产生了超过8 µM的NO。通常，抗增殖活性在一定程度上与NO的释放呈正相关。对细胞凋亡相关机制的进一步深入研究表明，15a以浓度依赖的方式引起S期细胞周期停滞，并通过线粒体相关途径显着诱导细胞凋亡。人类凋亡蛋白阵列测定也证明了15a增加了促凋亡Bax，Bad，HtrA2和Trail R2 / DR5的表达水平。过氧化氢酶和细胞周期阻滞剂claspin的表达同样被上调。平衡而言，15a通过内源性途径和外源性途径诱导K562细胞死亡。
• Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease
  作者：Xiao-Bing Wang、Fu-Cheng Yin、Ming Huang、Neng Jiang、Jin-Shuai Lan、Ling-Yi Kong

  DOI：10.1039/c9md00441f

  日期：——

  simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood–brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's

  设计，合成并评估了一系列色酮和多奈哌齐杂化物，作为多能胆碱酯酶（ChE）和单胺氧化酶（MAO）抑制剂，可用于治疗阿尔茨海默氏病（AD）。体外研究表明，这些化合物中的绝大多数对BuChE和AChE表现出有效的抑制活性，并且对h MAO-B具有明显的选择性抑制作用。特别地，化合物5c呈现出对ChE抑制的最平衡的电位（BuChE：IC 50 = 5.24μM； AChE：IC 50 = 0.37μM）和h MAO-B选择性（IC 50 = 0.272μM，SI = 247）。分子建模和动力学研究表明5c是一种混合型抑制剂，可同时与AChE的外围和活性位点结合。它也是一种竞争性抑制剂，占据了MAO-B的底物和入口腔。此外，化合物5c可以穿透血脑屏障（BBB），并且对大鼠嗜铬细胞瘤（PC12）细胞显示出低毒性。总而言之，这些结果表明化合物5c可能是希望的多靶点候选药物，可能对阿尔茨海默氏病的治疗产生影响。
• Domino Reactions of Chromone-3-carboxylic Acids with Aminoheterocycles: Synthesis of Heteroannulated Pyrido[2,3-<i>c</i> ]coumarins and their Optical and Biological Activity
  作者：Mariia Miliutina、Julia Janke、Elena Chirkina、Sidra Hassan、Syeda Abida Ejaz、Shafi Ullah Khan、Jamshed Iqbal、Aleksej Friedrich、Stefan Lochbrunner、Anton Ivanov、Alexander Villinger、Joanna Lecka、Jean Sévigny、Peter Langer

  DOI：10.1002/ejoc.201701276

  日期：2017.12.22

  A variety of new heteroannulated pyrido[2,3‐c]coumarins have been prepared by the domino reactions of chromone‐3‐carboxylic acids with aminoheterocycles

  色酮-3-羧酸与氨基杂环的多米诺反应制备了各种新的杂吡啶并[2,3- c ]香豆素
• Synthesis of 3,3′-carbonyl-bis(chromones) and their activity as mammalian alkaline phosphatase inhibitors
  作者：Mariia Miliutina、Syeda Abida Ejaz、Viktor O. Iaroshenko、Alexander Villinger、Jamshed Iqbal、Peter Langer

  DOI：10.1039/c5ob01350j

  日期：——

  Hitherto unknown 3,3′-carbonyl-bis(chromones) 8, dimeric chromones bridged by a carbonyl group, were prepared by reaction of chromone-3-carboxylic acid chloride with 3-(dimethylamino)-1- (2-hydroxyphenyl)-2-propen-1-ones 9. The method is generally applicable for the synthesis of novel symmetrical or non-symmetrical products which were found to inhibit mammalian alkaline phosphatases.

  通过色酮-3-羧酸氯与3-（二甲基氨基）-1-（2-羟苯基）-反应，制备了迄今未知的3，3′-羰基-双（色酮）8，其是通过羰基桥接的二聚色酮。 2丁1酮9。该方法通常适用于发现抑制哺乳动物碱性磷酸酶的新型对称或非对称产物的合成。
• 具有潜在铁螯合活性的单胺氧化酶B抑制剂及其应用
  申请人：浙江工业大学

  公开号：CN114149417A

  公开（公告）日：2022-03-08

  本发明合成了一类具有铁离子螯合活性的单胺氧化酶抑制剂，创新性地将具有铁离子螯合活性的吡啶酮衍生物与具有MAO‑B抑制活性的色酮母核有机结合在一起，对于发病机制复杂的阿尔茨海默症以及帕金森等神经退行性疾病具有显著优势。