4-chloro-7-methyl-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: 4-chloro-7-methyl-2H-chromen-2-one
• 英文别名: 4-Chloro-7-methylchromen-2-one
• 化学式: C₁₀H₇ClO₂
• 分子量: 194.617
• InChiKey: HJQZURKFLMCBMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-7-methyl-2H-chromen-2-one 在 叔丁基氯化镁 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 16.5h， 生成 methyl 2-(((2-(methyl(7-methyl-2-oxo-2H-chromen-4-yl)amino)ethoxy)(phenoxy)phosphoryl)amino)propanoate
  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：

  4-羟基-7-甲基香豆素 在 三氯氧磷 、 三乙胺 作用下， 反应 4.67h， 生成 4-chloro-7-methyl-2H-chromen-2-one
  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

• Discovery and SAR study of piperidine-based derivatives as novel influenza virus inhibitors
  作者：Guoxin Wang、Longjian Chen、Tongmei Xian、Yujie Liang、Xintao Zhang、Zhen Yang、Ming Luo

  DOI：10.1039/c4ob01079e

  日期：——

  A series of piperidine-based derivatives were identified as novel and potent inhibitors of the influenza virus through structural modification of a compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure–activity relationship (SAR) studies suggested that the ether linkage between the quinoline and piperidine is critical for the inhibitory activity. The optimized compound tert-butyl 4-(quinolin-4-yloxy)piperidine-1-carboxylate 11e had an excellent inhibitory activity against influenza virus infection from a variety of influenza virus strains, with EC50 values as low as 0.05 μM. The selectivity index value (SI = MLD50/EC50) of 11e is over 160 000 based on cytotoxicity, measured by MTT assays of three cell lines. We carried out a time-of-addition experiment to delineate the mechanism of inhibition. The result indicates that 11e interferes with the early to middle stage of influenza virus replication.

  一系列基于哌啶的衍生物被鉴定为新型的、强效的流感病毒抑制剂。这些衍生物是通过对一种从高通量筛选中选出的化合物进行结构修饰得到的。合成并确认了各种类似物作为抑制剂。构效关系(SAR)研究表明，喹啉与哌啶之间的醚键对于抑制活性至关重要。优化的化合物叔丁基 4-(喹啉-4-基氧)哌啶-1-羧酸酯 11e 对多种流感病毒株的流感病毒感染具有出色的抑制活性，EC50 值低至 0.05 μM。根据三种细胞系的 MTT 试验测得的细胞毒性，11e 的选择指数值(SI = MLD50/EC50)超过 160,000。我们进行了一项添加时间实验来阐明抑制机制。结果表明，11e干扰了流感病毒复制的早期到中期阶段。
• 10.1039/d4ob00942h
  作者：Raji Reddy, Chada、Edhara, Venkatareddy、Kumari, Ankita、Patil, Amol D.、Thandavamurthy, Karthikeyan

  DOI：10.1039/d4ob00942h

  日期：——

  the assembly of 4,5-fused coumarin scaffolds. This protocol employs silver-catalyzed oxidative decarboxylation for the generation of alkyl radicals from carboxylic acids, which were used as radical precursors. This method has also been extended to a diverse range of carbon-centered radicals generated from 2-oxo acids, a 1,3-dicarbonyl compound, isopropanol and acetone.

  一种前所未有的自由基促进策略，涉及N-丙烯酰基-4-氨基香豆素的多米诺烷基化/分子内 C5 环化，已被设计用于组装 4,5-融合香豆素支架。该方案采用银催化的氧化脱羧作用从用作自由基前体的羧酸生成烷基自由基。该方法还扩展到由 2-含氧酸、1,3-二羰基化合物、异丙醇和丙酮产生的各种碳中心自由基。
• Mulwad; Mahaddalkar, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 1, p. 29 - 32
  作者：Mulwad、Mahaddalkar

  DOI：——

  日期：——
• ITO KEIICHI; HARIYA JUNKO, HETEROCYCLES, 26<!>,(1987) N 1, 35-38
  作者：ITO KEIICHI、 HARIYA JUNKO

  DOI：——

  日期：——
• 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.