4-(5,6,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl morpholine-4-carboxylate

• 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: 4-(5,6,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl morpholine-4-carboxylate
• 英文别名: 4-Morpholinecarboxylic acid-4-(5,6,7-trihydroxy-4-oxo-4H-1-benzopyran-2-yl)phenyl ester (7f)；[4-(5,6,7-trihydroxy-4-oxochromen-2-yl)phenyl] morpholine-4-carboxylate
• 化学式: C₂₀H₁₇NO₈
• 分子量: 399.357
• InChiKey: XUCLCXLEARIZOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  野黄芩素 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 二苯醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 4-(5,6,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl morpholine-4-carboxylate
  参考文献：
  名称：

  作为电压门控 Nav1.5 和 Cav1.2 通道阻滞剂的新型黄芩素类似物的合成和体内抗心律失常活性评价

  摘要：

  恶性心律失常具有较高的发病率和死亡率，对人类健康构成重大威胁。黄芩素是从黄芩中分离得到的黄芩素的代谢产物，对心血管疾病具有良好的治疗作用，并且可以进一步代谢为甲基化形式。基于灯盏乙素体内代谢物，设计了一系列22种新型羟基取代的灯盏乙素衍生物，通过灯盏乙素支架与FDA批准的抗心律失常药物药效团的结合合成，并通过大鼠数量分析评价其抗心律失常活性。心律失常恢复时间，对应于氯化钡诱发心律失常大鼠模型中的恢复时间和维持时间，以及乌头碱诱发心律失常大鼠模型中诱发VP、VT、VF和CA所需的乌头碱累积剂量。所有设计的化合物均能缩短氯化钡诱导的心律失常连续时间，表明灯盏花素的4'-羟基取代基具有快速起效的抗心律失常作用。此外，几乎所有化合物都能使 HR、RR、QRS、QT 和 QTc 间期以及 P/T 波振幅正常化。最有前途的化合物10e表现出最好的抗心律失常活性，具有长期疗效和极低的细胞毒性，优于阳性对

  DOI：

  10.3390/molecules28217417

文献信息

• Synthesis of scutellarein derivatives to increase biological activity and water solubility
  作者：Zhi-Hao Shi、Nian-Guang Li、Qian-Ping Shi、Wei Zhang、Ze-Xi Dong、Yu-Ping Tang、Peng-Xuan Zhang、Ting Gu、Wen-Yu Wu、Fang Fang、Xin-Xue、He-Min Li、Jian-Ping Yang、Jin-Ao Duan

  DOI：10.1016/j.bmc.2015.09.047

  日期：2015.11

  In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease. (C) 2015 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease
  作者：Zhi-pei Sang、Xiao-ming Qiang、Yan Li、Bei Wu、Hui Zhang、Ming-gao Zhao、Yong Deng

  DOI：10.1111/cbdd.12580

  日期：2015.11

  A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget‐directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide‐induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 ± 0.03 μm and 22.1 ± 0.15 μm, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step‐down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD.
• Synthesis and In Vivo Antiarrhythmic Activity Evaluation of Novel Scutellarein Analogues as Voltage-Gated Nav1.5 and Cav1.2 Channels Blockers
  作者：Wei Yang、Wenping Wang、Song Cai、Peng Li、Die Zhang、Jinhua Ning、Jin Ke、Anguo Hou、Linyun Chen、Yunshu Ma、Wenbin Jin

  DOI：10.3390/molecules28217417

  日期：——

  hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced

  恶性心律失常具有较高的发病率和死亡率，对人类健康构成重大威胁。黄芩素是从黄芩中分离得到的黄芩素的代谢产物，对心血管疾病具有良好的治疗作用，并且可以进一步代谢为甲基化形式。基于灯盏乙素体内代谢物，设计了一系列22种新型羟基取代的灯盏乙素衍生物，通过灯盏乙素支架与FDA批准的抗心律失常药物药效团的结合合成，并通过大鼠数量分析评价其抗心律失常活性。心律失常恢复时间，对应于氯化钡诱发心律失常大鼠模型中的恢复时间和维持时间，以及乌头碱诱发心律失常大鼠模型中诱发VP、VT、VF和CA所需的乌头碱累积剂量。所有设计的化合物均能缩短氯化钡诱导的心律失常连续时间，表明灯盏花素的4'-羟基取代基具有快速起效的抗心律失常作用。此外，几乎所有化合物都能使 HR、RR、QRS、QT 和 QTc 间期以及 P/T 波振幅正常化。最有前途的化合物10e表现出最好的抗心律失常活性，具有长期疗效和极低的细胞毒性，优于阳性对