4-((2-hydroxyethyl)(methyl)amino)coumarin

• 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: 4-((2-hydroxyethyl)(methyl)amino)coumarin
• 英文别名: 4-[2-Hydroxyethyl(methyl)amino]chromen-2-one
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: YCPRJILJAFWIDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((2-hydroxyethyl)(methyl)amino)coumarin 、 chlorophenylphosphoryl (P->N)-L-valine methyl ester 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 生成 methyl 3-methyl-2-(((2-(methyl(2-oxo-2H-chromen-4-yl)amino)ethoxy)(phenoxy)phosphoryl)amino)butanoate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents

  摘要：

  A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the K-m of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-N-acetylglucosamine, and the result of the K-i showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 p,g/mL to 2 mu g/MI while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.027
• 作为产物：
  描述：

  苯酚 在 potassium carbonate 、 zinc(II) chloride 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 4.67h， 生成 4-((2-hydroxyethyl)(methyl)amino)coumarin
  参考文献：
  名称：

  Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents

  摘要：

  A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the K-m of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-N-acetylglucosamine, and the result of the K-i showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 p,g/mL to 2 mu g/MI while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.027

文献信息

• Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents
  作者：Qinggang Ji、Zhiqiang Ge、Zhixing Ge、Kaizhi Chen、Hualong Wu、Xiaofei Liu、Yanrong Huang、Lvjiang Yuan、Xiaolan Yang、Fei Liao

  DOI：10.1016/j.ejmech.2015.11.027

  日期：2016.1

  A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the K-m of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-N-acetylglucosamine, and the result of the K-i showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 p,g/mL to 2 mu g/MI while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational. (C) 2015 Elsevier Masson SAS. All rights reserved.