(E)-7-(3,7-dimethylocta-2,6-dienyloxy)-4-phenyl-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: (E)-7-(3,7-dimethylocta-2,6-dienyloxy)-4-phenyl-2H-chromen-2-one
• 英文别名: 7-{[(2E)-3,7-dimethyl-2,6-octadien-1-yl]oxy}-4-phenyl-2H-chromen-2-one；7-[(2E)-3,7-dimethylocta-2,6-dienoxy]-4-phenylchromen-2-one
• 化学式: C₂₅H₂₆O₃
• 分子量: 374.48
• InChiKey: KZCXEBBZROILCL-XMHGGMMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯甲酰乙酸乙酯 在 硫酸 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 5.25h， 生成 (E)-7-(3,7-dimethylocta-2,6-dienyloxy)-4-phenyl-2H-chromen-2-one
  参考文献：
  名称：

  7-萜烯香豆素的降血糖活性研究。

  摘要：

  天然和合成香豆素通常被认为是获得具有降血糖活性的药物的特殊支架。香豆素的化学修饰通常会导致抗糖尿病药物具有更高的功效。在目前的工作中，合成了二十种单萜取代的 7-羟基香豆素。一种使用 Mitsunobu 反应的新方法被证明可有效合成目标化合物。所有合成的化合物都在口服葡萄糖耐量试验中进行了评估，其中两个含有香叶基和 (-)-月桂烯基取代基的化合物显示出体内降血糖作用。这些化合物的可能作用机制可能包括抑制 DPP IV，这在体外试验中得到证实。

  DOI：

  10.3390/molecules27248663

文献信息

• Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy
  作者：Tatyana M. Khomenko、Alexandra L. Zakharenko、Arina A. Chepanova、Ekaterina S. Ilina、Olga D. Zakharova、Vasily I. Kaledin、Valeriy P. Nikolin、Nelly A. Popova、Dina V. Korchagina、Jóhannes Reynisson、Raina Chand、Daniel M. Ayine-Tora、Jinal Patel、Ivanhoe K. H. Leung、Konstantin P. Volcho、Nariman F. Salakhutdinov、Olga I. Lavrik

  DOI：10.3390/ijms21010126

  日期：——

  Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC50 0.62 µM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons.

  酪氨酸-DNA磷酸二酯酶1（Tdp1）是人类中重要的DNA修复酶，是开发新的化疗增敏剂的当前和有希望的抑制靶点，因为它能够去除由拓扑异构酶1（Top1）毒素（如托泊替康和伊立曲汀）引起的DNA损伤。在这里，我们报告了我们对合成和表征结合芳基香豆素（新黄酮类）和单萜类基团的新Tdp1抑制剂的工作。我们的结果显示，它们是有效的Tdp1抑制剂，其IC50值在亚微摮摩尔范围内。对小鼠进行的体内实验显示，化合物3ba（IC50值为0.62 µM）显著增加了托泊替康对Krebs-2腹水瘤模型的抗肿瘤效果。我们的结果进一步加强了Tdp1是一个可药用的靶点，并有潜力作为与Top1毒素联合使用的临床有效的辅助治疗方法的论点。
• The Study of Hypoglycemic Activity of 7-Terpenylcoumarins
  作者：Sergey Kuranov、Mariya Marenina、Dmitriy Ivankin、Mikhail Blokhin、Sergey Borisov、Tatyana Khomenko、Olga Luzina、Mikhail Khvostov、Konstantin Volcho、Tatyana Tolstikova、Nariman Salakhutdinov

  DOI：10.3390/molecules27248663

  日期：——

  privileged scaffolds for obtaining pharmacological agents with hypoglycemic activity. Chemical modification of coumarins often leads to antidiabetic agents with greater efficacy. In the present work, twenty monoterpene-substituted 7-hydroxycoumarins were synthesized. A new approach using the Mitsunobu reaction was shown to be effective for the synthesis of target compounds. All of the synthesized compounds

  天然和合成香豆素通常被认为是获得具有降血糖活性的药物的特殊支架。香豆素的化学修饰通常会导致抗糖尿病药物具有更高的功效。在目前的工作中，合成了二十种单萜取代的 7-羟基香豆素。一种使用 Mitsunobu 反应的新方法被证明可有效合成目标化合物。所有合成的化合物都在口服葡萄糖耐量试验中进行了评估，其中两个含有香叶基和 (-)-月桂烯基取代基的化合物显示出体内降血糖作用。这些化合物的可能作用机制可能包括抑制 DPP IV，这在体外试验中得到证实。
• AGENT FOR PROMOTING OSTEOBLAST DIFFERENTIATION, PHARMACEUTICAL COMPOSITION FOR PROMOTING BONE FORMATION, AND FOOD FOR SPECIAL DIETARY USE CONTAINING AURAPTENE ANALOG AS ACTIVE INGREDIENT
  申请人：Woo Je-Tae

  公开号：US20130102796A1

  公开（公告）日：2013-04-25

  Agents or pharmaceutical compositions for promoting osteoblast differentiation include purified auraptene or coumarin analogs thereof represented by the following formula 1: wherein R1 represents a hydrogen, a hydroxy, a methoxy, a methyl, an ethyl, a propyl, a carboxyl, a carboxymethyl, or a carboxyethyl; R2 represents a hydrogen, a hydroxy, a methoxy, a methyl, an ethyl, a propyl, a carboxyl, a carboxymethyl, a carboxyethyl or a coumarinyl; R3 represents a hydrogen, a hydroxy, a methoxy, a methyl, an ethyl, a propyl, a carboxyl, a carboxymethyl or a carboxyethyl; and R4 represents a hydrogen, a C 1 -C 15 liner or branched alkyl, an alkenyl, an alkadienyl or an alkatrienyl.
• US8729279B2
  申请人：——

  公开号：US8729279B2

  公开（公告）日：2014-05-20
• New Inhibitors of Respiratory Syncytial Virus (RSV) Replication Based on Monoterpene-Substituted Arylcoumarins
  作者：Tatyana M. Khomenko、Anna A. Shtro、Anastasia V. Galochkina、Yulia V. Nikolaeva、Anzhelika V. Garshinina、Sophia S. Borisevich、Dina V. Korchagina、Konstantin P. Volcho、Nariman F. Salakhutdinov

  DOI：10.3390/molecules28062673

  日期：——

  Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection. Usually harmless to adults, the RSV infection can be dangerous to children under 3 years of age and elderly people over 65 years of age, often causing serious problems, even death. At present, there are no vaccines and specific chemotherapeutic agents for the treatment of this disease, so the search for low-molecular weight compounds to combat RSV is a challenge. In this work, we have shown, for the first time, that monoterpene-substituted arylcoumarins are efficient RSV replication inhibitors at low micromolar concentrations. The most active compound has a selectivity index of about 200 and acts most effectively at the early stages of infection. The F protein of RSV is a potential target for these compounds, which is also confirmed by molecular docking and molecular dynamics simulation data.

  呼吸道合胞病毒（RSV）每年都会引起呼吸道感染流行。通常情况下，RSV 对成人无害，但对 3 岁以下儿童和 65 岁以上老人来说，RSV 感染可能很危险，往往会造成严重问题，甚至死亡。目前，还没有治疗这种疾病的疫苗和特异性化疗药物，因此寻找抗 RSV 的低分子量化合物是一项挑战。在这项研究中，我们首次发现单萜取代的芳基香豆素类化合物在低微摩尔浓度下是高效的 RSV 复制抑制剂。活性最高的化合物的选择性指数约为 200，在感染的早期阶段发挥最有效的作用。RSV 的 F 蛋白是这些化合物的潜在靶标，分子对接和分子动力学模拟数据也证实了这一点。