2-(4-(dimethylamino)phenyl)-7-hydroxy-4H-chromen-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(4-(dimethylamino)phenyl)-7-hydroxy-4H-chromen-4-one
• 英文别名: 2-[4-(dimethylamino)phenyl]-7-hydroxy-4H-1-benzopyran-4-one；2-[4-(dimethylamino)phenyl]-7-hydroxychromen-4-one
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: PHJROYPYUHPDOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-(dimethylamino)phenyl)-7-hydroxy-4H-chromen-4-one 在 hydrazine hydrate 、 potassium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 、 丙酮 为溶剂， 反应 14.0h， 生成
  参考文献：
  名称：

  Antioxidant and Cardioprotective Evaluation of Some N-(3-Chloro-2-oxo-4- arylazetidin-1-yl)-2-[(4-oxo-2-aryl-4H-chromen-7-yl)oxy]acetamide Derivatives

  摘要：

  一系列N-(3-氯-2-氧代-4-芳基氮杂环丙氨基)-2-[(4-氧代-2-芳基-4H-香豆素-7-基)氧基]乙酰胺衍生物[SLP VI 1(a-d)-2(a-d)]是通过中间产物席夫碱从7-羟基黄酮衍生物合成的。合成的化合物通过DPPH自由基清除实验进行了体外抗氧化性质的研究。具有良好抗氧化活性的标题化合物进一步通过多柔比星诱导的心脏毒性进行了可能的心脏保护效应评估。在50 μg/kg剂量下口服测试化合物后，所有生化变化均得到了正常化。结果显示心脏组织匀浆中抗氧化酶催化酶和超氧化物歧化酶显著增加(p < 0.05)。这些观察结果使我们得出结论，合成的SLP VI 1b、VI 1c、VI 2b和VI 2d衍生物对多柔比星诱导的心脏毒性具有心脏保护活性。此外，尝试对合成的化合物进行体外研究，以预测测试配体与潜在心血管蛋白靶点之间的相互作用，使用分子对接工具。标题化合物与MAP激酶P38和PKCβ心血管靶点具有良好的结合亲和力。

  DOI：

  10.14233/ajchem.2022.23437
• 作为产物：
  描述：

  4-二甲氨基苯甲酸甲酯 在 硫酸 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 反应 29.0h， 生成 2-(4-(dimethylamino)phenyl)-7-hydroxy-4H-chromen-4-one
  参考文献：
  名称：

  A rational approach to the design of flavones as xanthine oxidase inhibitors

  摘要：

  In the light of previous QSAR studies on flavones as inhibitors of xanthine oxidase, we synthesized and tested a new series of 7-hydroxyflavones carrying a wide and balanced variety of substituents (pi, sigma(p)) at the 4' position in order to explore the effect of substituents at this position on the xanthine oxidase inhibitory activity. The results of pK(a) determinations show that the electronic effects of the substituents are not transferred to the hydroxyl at C7, previously found to be fundamental for activity. An excellent correlation is found between molar refractivity of the substituents and the inhibitory activity. These results, applied to the more active 5,7-dihydroxyflavones, allowed the design and synthesis of a very active inhibitor, with an IC50 in the nanomolar range. On interpretative grounds, C4' substituents of flavones are involved in dispersion interactions with the enzyme. The calculation of quantum chemical polarizabilities and solvent accessible surface areas suggests the existence of pi-pi stacking interactions with an aromatic aminoacidic residue of the enzyme.

  DOI：

  10.1016/0223-5234(96)85878-8

文献信息

• Synthesis and Antiproliferative Activity of Some Dihydro-1H-furo[2,3-c]pyrazole-Flavone Hybrids
  作者：Venkata Swamy Tangeti、D. Vasundhara、K.V.V.V. Satyanarayana、Kaja Srinivas Pavan Kumar

  DOI：10.14233/ajchem.2017.20550

  日期：——

  A new series of dihydro-1H-furo[2,3-c]pyrazole-flavone hybrids were synthesized from one-pot four-component reaction of b-keto ester (1), hydrazine (2), 7-hydroxy 8-formyl flavones (3), pyridiniumylide (4) in presence of NEt3 as catalyst under ethanol reflux conditions and their antiproliferative properties were evaluated against human cancer cell lines, namely, laryngeal carcinoma (Hep2), lung adenocarcinoma (A549) and cervical cancer (HeLa). The best among them, furo[2,3-c]pyrazole-flavone with C4-methoxy substitution was selected for further structure activity relationship (SAR) studies. Among the derivatives, (4S,5S)-ethyl 4-(7-hydroxy-5-methoxy-4-oxo-2-(2,4,6-trimethoxyphenyl)-4H-chromen-8-yl)-3-methyl-4,5-dihydro-1H-furo[2,3-c]pyrazole-5-carboxylate (8r) showed most potent cytotoxic activity against all three cancer cell lines. Toxicity studies revealed that the dihydro-1H-furo[2,3-c]pyrazole-flavones are specifically target the cancer cell lines.

  一系列二氢-1H-呋喃[2,3-c]吡唑-黄酮杂合物通过一锅四组分反应合成，反应物包括β-酮酯（1）、肼（2）、7-羟基-8-醛黄酮（3）和吡啶亚胺（4），在三乙胺（NEt3）催化下于乙醇回流条件下进行。随后评估了这些化合物对人类癌细胞系的抗增殖活性，包括喉癌（Hep2）、肺腺癌（A549）和宫颈癌（HeLa）。在这些化合物中，C4-取代的甲氧基二氢-1H-呋喃[2,3-c]吡唑-黄酮被选为进一步结构-活性关系（SAR）研究的对象。在这些衍生物中，(4S,5S)-乙基4-(7-羟基-5-甲氧基-4-氧基-2-(2,4,6-三甲氧基苯基)-4H-香豆烯-8-基)-3-甲基-4,5-二氢-1H-呋喃[2,3-c]吡唑-5-羧酸酯（8r）对所有三种癌细胞系表现出最强的细胞毒活性。毒性研究表明，二氢-1H-呋喃[2,3-c]吡唑-黄酮特别靶向癌细胞系。
• Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents
  作者：Wen Luo、Ya-Bin Su、Chen Hong、Run-Guo Tian、Lei-Peng Su、Yue-Qiao Wang、Yang Li、Jun-Jie Yue、Chao-Jie Wang

  DOI：10.1016/j.bmc.2013.09.061

  日期：2013.12

  A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 mu M for AChE and 0.82-11.45 mu M for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced A beta aggregation inhibitory activity at 20 mu M with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.
• Inhibitory effect of flavonoids on human glutaminyl cyclase
  作者：Manman Li、Yao Dong、Xi Yu、Yongdong Zou、Yizhi Zheng、Xianzhang Bu、Junmin Quan、Zhendan He、Haiqiang Wu

  DOI：10.1016/j.bmc.2016.03.064

  日期：2016.5

  Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer's disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4' (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure-activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC. (C) 2016 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents
  作者：Wen Luo、Ting Wang、Chen Hong、Ya–Chen Yang、Ying Chen、Juan Cen、Song–Qiang Xie、Chao–Jie Wang

  DOI：10.1016/j.ejmech.2016.06.022

  日期：2016.10

  A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced beta-amyloid (A beta) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced A beta aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD. (C) 2016 Elsevier Masson SAS. All rights reserved.
• A rational approach to the design of flavones as xanthine oxidase inhibitors
  作者：L Costantino、G Rastelli、A Albasini

  DOI：10.1016/0223-5234(96)85878-8

  日期：1996.1

  In the light of previous QSAR studies on flavones as inhibitors of xanthine oxidase, we synthesized and tested a new series of 7-hydroxyflavones carrying a wide and balanced variety of substituents (pi, sigma(p)) at the 4' position in order to explore the effect of substituents at this position on the xanthine oxidase inhibitory activity. The results of pK(a) determinations show that the electronic effects of the substituents are not transferred to the hydroxyl at C7, previously found to be fundamental for activity. An excellent correlation is found between molar refractivity of the substituents and the inhibitory activity. These results, applied to the more active 5,7-dihydroxyflavones, allowed the design and synthesis of a very active inhibitor, with an IC50 in the nanomolar range. On interpretative grounds, C4' substituents of flavones are involved in dispersion interactions with the enzyme. The calculation of quantum chemical polarizabilities and solvent accessible surface areas suggests the existence of pi-pi stacking interactions with an aromatic aminoacidic residue of the enzyme.