2-([1,1′-biphenyl]-4-yl)-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-([1,1′-biphenyl]-4-yl)-7-hydroxy-4H-chromen-4-one
• 英文别名: 2-([1,1'-biphenyl]-4-yl)-7-hydroxy-4H-chromen-4-one；7-Hydroxy-2-(4-phenylphenyl)chromen-4-one
• 化学式: C₂₁H₁₄O₃
• 分子量: 314.34
• InChiKey: MJBRZBKZOVAHSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-([1,1′-biphenyl]-4-yl)-7-hydroxy-4H-chromen-4-one 在 potassium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 18.0h， 生成 2-(biphenyl-4-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one
  参考文献：
  名称：

  Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities

  摘要：

  A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4-Hchromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64 mu M for AChE and 0.42 mu M for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10 mu M. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.031
• 作为产物：
  描述：

  间苯二酚 在 sodium hydroxide 、 zinc(II) chloride 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 24.0h， 生成 2-([1,1′-biphenyl]-4-yl)-7-hydroxy-4H-chromen-4-one
  参考文献：
  名称：

  Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities

  摘要：

  A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4-Hchromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64 mu M for AChE and 0.42 mu M for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10 mu M. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.031

文献信息

• Nitrogen‐containing flavonoid and their analogs with diverse B‐ring in acetylcholinesterase and butyrylcholinesterase inhibition
  作者：Qiao‐Qiao Lu、Ya‐Ming Chen、Hao‐Ran Liu、Jian‐Ye Yan、Pei‐Wu Cui、Qian‐Fan Zhang、Xiao‐Hui Gao、Xing Feng、Ying‐Zi Liu

  DOI：10.1002/ddr.21726

  日期：2020.12

  2‐anthryl‐chromone derivatives against AChE significantly decreased, while that of 2‐biphenyl chromone derivatives with 7‐substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development

  在这项研究中，设计、合成了一系列含有6或7个取代叔胺侧链的新型黄酮（2-苯基色酮）、2-萘基色酮、2-蒽基色酮或2-联苯色酮衍生物，并评估乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）抑制。结果表明，色酮支架上连接的芳环的改变对生物活性产生显着影响。与黄酮类化合物相比，2-萘基色酮、2-蒽基色酮衍生物对AChE的抑制活性显着降低，而带有7位取代叔胺侧链的2-联苯色酮衍生物的抑制活性优于相关黄酮类衍生物。对于所有新合成的化合物，叔胺侧链的位置明显影响抑制AChE的活性。上述结果为新型AChE抑制剂的进一步开发提供了有价值的信息。在新合成的化合物中，化合物5a具有有效的AChE抑制作用（IC 50 = 1.29 ± 0.10 μmol/L），并且对AChE的选择性高于BChE（选择性比：27.96）。化合物5a的酶动力学研究表明它对 AChE 产生混合型抑制作用。
• 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.
• Synthesis and Identification of New Flavonoids Targeting Liver X Receptor β Involved Pathway as Potential Facilitators of Aβ Clearance with Reduced Lipid Accumulation
  作者：Yun Hu、Yaqi Yang、Yanjun Yu、Gesi Wen、Nana Shang、Wei Zhuang、Dihan Lu、Binhua Zhou、Baoxia Liang、Xin Yue、Feng Li、Jun Du、Xianzhang Bu

  DOI：10.1021/jm301913k

  日期：2013.8.8

  Alzheimer's disease (AD) is associated with impaired A beta degradation in the brain. Enhancing the process of A beta clearance is an attractive potential AD therapy. Treatment with LXR agonists may reduce A beta levels in vivo. However, the clinical potential of many LXR agonists is limited because of their nonselective actions on LXR alpha/beta, which lead to undesired hepatic lipogenesis via LXR alpha-dependent pathways. In this study, ABCA1 up-regulators were identified from a series of flavonoids and were found to preferentially activate LXR beta and up-regulate expression of ABCA1 and apoE in different cell lines. Further investigations confirmed that these compounds facilitate intracellular A beta clearance in A beta-loaded BV2 cells. Administration of compound 19 reduced total brain A beta and plaque burden in APP/PS1 double transgenic mice, associated with elevated ABCA1 and apoE expression. Compared with the nonselective LXR agonists, the active compounds reported here induced less accumulation of undesired lipids and triglycerides in HepG2 cells.
• Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities
  作者：Wen Luo、Ying Chen、Ting Wang、Chen Hong、Li-Ping Chang、Cong-Cong Chang、Ya-Cheng Yang、Song-Qiang Xie、Chao-Jie Wang

  DOI：10.1016/j.bmc.2015.12.031

  日期：2016.2

  A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4-Hchromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64 mu M for AChE and 0.42 mu M for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10 mu M. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease. (c) 2015 Elsevier Ltd. All rights reserved.