3-benzyl-4-ethyl-7-hydroxy-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-benzyl-4-ethyl-7-hydroxy-2H-chromen-2-one
• 英文别名: 3-benzyl-4-ethyl-7-hydroxycoumarin；3-Benzyl-4-ethyl-7-hydroxychromen-2-one
• 化学式: C₁₈H₁₆O₃
• 分子量: 280.323
• InChiKey: QUVQIQDMNPNFAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  二甲氨基甲酰氯 、 3-benzyl-4-ethyl-7-hydroxy-2H-chromen-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以94.6%的产率得到3-benzyl-4-ethyl-2-oxo-2H-chromen-7-yl dimethylcarbamate
  参考文献：
  名称：

  Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

  摘要：

  为了寻找新型抗病毒药物，设计并合成了一系列别构MEK1抑制剂。基于对接结果，对香豆素支架进行了多次优化。某些衍生物在适当的酶学测定中表现出优秀的MEK1结合亲和力，并在细胞测定中对ERK通路表现出明显的抑制效应。这些化合物还显著抑制了HEK293和RD细胞中的病毒（EV71）复制。几种化合物显示出作为病毒感染性疾病治疗剂的潜力，其中最有效的化合物18在MEK1结合测定中的IC50值为54.57 nM。

  DOI：

  10.3390/molecules18056057
• 作为产物：
  描述：

  丙酰乙酸乙酯 在 硫酸 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.25h， 生成 3-benzyl-4-ethyl-7-hydroxy-2H-chromen-2-one
  参考文献：
  名称：

  Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

  摘要：

  为了寻找新型抗病毒药物，设计并合成了一系列别构MEK1抑制剂。基于对接结果，对香豆素支架进行了多次优化。某些衍生物在适当的酶学测定中表现出优秀的MEK1结合亲和力，并在细胞测定中对ERK通路表现出明显的抑制效应。这些化合物还显著抑制了HEK293和RD细胞中的病毒（EV71）复制。几种化合物显示出作为病毒感染性疾病治疗剂的潜力，其中最有效的化合物18在MEK1结合测定中的IC50值为54.57 nM。

  DOI：

  10.3390/molecules18056057

文献信息

• Synthesis of Substituted Coumarins via Brønsted Acid Mediated Condensation of Allenes with Substituted Phenols or Anisoles
  作者：Sundae Kim、Dongjin Kang、Chang-Hee Lee、Phil Ho Lee

  DOI：10.1021/jo301086k

  日期：2012.8.3

  Coumarins were obtained from the condensation of electron-rich arenes with allenes in the presence of TfOH in good yield. Depending on the substituent pattern of allenes employed, the general synthetic method of 4-substituted and 3,4-disubstituted 3-arylcoumarins has been developed. Readily available allenes were employed as the three-carbon atom sources constituting the coumarin skeleton.

  在TfOH存在下，富电子芳烃与丙二烯的缩合可得到香豆素。根据所用的烯的取代基样式，已经开发了4-取代和3，4-二取代的3-芳基香豆素的一般合成方法。使用现成的丙二烯作为构成香豆素骨架的三碳原子源。
• Discovery and structure–activity relationship of coumarin derivatives as TNF-α inhibitors
  作者：Jie-Fei Cheng、Mi Chen、David Wallace、Sovouthy Tith、Thomas Arrhenius、Hirotaka Kashiwagi、Yoshiyuki Ono、Akira Ishikawa、Haruhiko Sato、Toshiro Kozono、Hediki Sato、Alex M. Nadzan

  DOI：10.1016/j.bmcl.2004.03.022

  日期：2004.5

  The discovery and structure-activity relationship of a novel series of coumarin-based TNF-alpha inhibitors is described. Starting from the initial lead la, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-alpha production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-alpha production in rats. (C) 2004 Elsevier Ltd. All rights reserved.
• [EN] AGENTS AND METHODS FOR TREATING ISCHEMIC AND OTHER DISEASES<br/>[FR] AGENTS ET MÉTHODES DE TRAITEMENT DE MALADIES ISCHÉMIQUES ET D'AUTRES MALADIES
  申请人：NONO INC

  公开号：WO2012174488A2

  公开（公告）日：2012-12-20

  This invention relates to compounds that modulate TRPM7 protein activity and use of the same for treatment or prophylaxis of ischemia, cancer, pain or glaucoma.
• Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
  作者：Chao Wang、Hao Zhang、Fengrong Xu、Yan Niu、Yun Wu、Xin Wang、Yihong Peng、Jing Sun、Lei Liang、Ping Xu

  DOI：10.3390/molecules18056057

  日期：——

  In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay.

  为了寻找新型抗病毒药物，设计并合成了一系列别构MEK1抑制剂。基于对接结果，对香豆素支架进行了多次优化。某些衍生物在适当的酶学测定中表现出优秀的MEK1结合亲和力，并在细胞测定中对ERK通路表现出明显的抑制效应。这些化合物还显著抑制了HEK293和RD细胞中的病毒（EV71）复制。几种化合物显示出作为病毒感染性疾病治疗剂的潜力，其中最有效的化合物18在MEK1结合测定中的IC50值为54.57 nM。