7-(2-(piperidin-1-yl)ethoxy)-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-4H-chromen-4-one | 41524-24-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 7-(2-(piperidin-1-yl)ethoxy)-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-4H-chromen-4-one
• 英文别名: 7-(2-Piperidin-1-ylethoxy)-3-[4-(2-piperidin-1-ylethoxy)phenyl]chromen-4-one
• CAS: 41524-24-7
• 化学式: C₂₉H₃₆N₂O₄
• 分子量: 476.616
• InChiKey: RVODBMMZZGFRMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  间苯二酚 在 三氟化硼乙醚 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 10.0h， 生成 7-(2-(piperidin-1-yl)ethoxy)-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-4H-chromen-4-one
  参考文献：
  名称：

  Synthetic analogs of daidzein, having more potent osteoblast stimulating effect

  摘要：

  A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of osteoblasts. Further, these three compounds did not show any estrogen agonistic activity, however had mild estrogen antagonistic effect. Out of the three compounds, 3c was found to maximally increase the mineralization of bone marrow osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of osteogenic genes including bone morphogenetic protein-2 and osteocalcin in osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis. Collectively, we demonstrate osteogenic activity of daidzein analogs at significantly lower concentrations than daidzein. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.008

文献信息

• Discovery of novel isoflavone derivatives as AChE/BuChE dual-targeted inhibitors: synthesis, biological evaluation and molecular modelling
  作者：Bo Feng、Xinpeng Li、Jie Xia、Song Wu

  DOI：10.1080/14756366.2017.1347163

  日期：2017.1.1

  AChE and BuChE are druggable targets for the discovery of anti-Alzheimer's disease drugs, while dual-inhibition of these two targets seems to be more effective. In this study, we synthesised a series of novel isoflavone derivatives based on our hit compound G from in silico high-throughput screening and then tested their activities by in vitro AChE and BuChE bioassays. Most of the isoflavone derivatives

  AChE和BuChE是发现抗阿尔茨海默氏病药物的可治疗靶标，而双重抑制这两个靶标似乎更有效。在这项研究中，我们通过计算机高通量筛选，基于命中化合物G合成了一系列新型异黄酮衍生物，然后通过体外AChE和BuChE生物测定法测试了它们的活性。大多数异黄酮衍生物对AChE和BuChE均显示中等抑制作用。其中，化合物16被确定为有效的AChE / BuChE双靶抑制剂（IC50：AChE为4.60μM； BuChE为5.92μM）。分子模型研究表明，化合物16可能具有更好的药代动力学特性，例如吸收，血脑屏障渗透和CYP2D6结合。在一起
• Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer's disease
  作者：Dongmei Wang、Min Hu、Xinpeng Li、Dan Zhang、Chengjuan Chen、Junmin Fu、Shuai Shao、Gaona Shi、Yu Zhou、Song Wu、Tiantai Zhang

  DOI：10.1016/j.ejmech.2019.02.053

  日期：2019.4

  synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylcholinesterase (AChE), neuroprotective effects and anti-neuroinflammatory properties. Among these derivatives, compound 9b exhibited the

  设计，合成和评估了一系列新颖的异黄酮类似物，将其作为治疗阿尔茨海默氏病的多靶标配体。体外评估表明，某些配体具有多功能特性，包括有效阻断组胺3受体（H3R），对乙酰胆碱酯酶（AChE）的出色抑制作用，神经保护作用和抗神经炎特性。在这些衍生物中，化合物9b表现出最高的H3R阻断能力（IC 50  = 0.27μM）和对AChE的良好抑制活性（IC 50  = 0.08μM）。此外，化合物9b通过抑制铜诱导的神经元损伤和抑制BV-2细胞中炎性因子的产生，对SH-SY5Y具有明显的神经保护作用。分子模型研究表明，9b是与H3R和AChE同时相互作用的混合型抑制剂。此外，体内数据显示，化合物9b在高达1000 mg / kg的剂量下不会对小鼠产生急性毒性，并且具有理想的药代动力学特性以及良好的血脑屏障（BBB）渗透性（log BB = 1.24± 0.07）。进一步的研究表明，用9b进行慢性口服治疗