methyl 3-(4-nitrobenzamido)propanoate | 60247-39-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 3-(4-nitrobenzamido)propanoate
• 英文别名: N-(p-Nitrobenzoyl)-O-methyl-β-alanin；N-(4-nitro-benzoyl)-β-alanine methyl ester；N-(4-Nitro-benzoyl)-β-alanin-methylester；methyl N-[(4-nitrophenyl)carbonyl]-beta-alaninate；methyl 3-[(4-nitrobenzoyl)amino]propanoate
• CAS: 60247-39-4
• 化学式: C₁₁H₁₂N₂O₅
• mdl: MFCD04791724
• 分子量: 252.227
• InChiKey: DLXQGTJGSQXOFN-UHFFFAOYSA-N

物化性质

• 沸点：
  464.6±30.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-nitrobenzamido)propanoate 在 N-甲基吗啉 、 palladium on activated charcoal 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.5h， 生成 methyl 3-(4-(1H-indole-2-carboxamido)benzamido)propanoate
  参考文献：
  名称：

  N-Phenyl-4,5-dibromopyrrolamides and N-Phenylindolamides as ATP Competitive DNA Gyrase B Inhibitors: Design, Synthesis, and Evaluation

  摘要：

  Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors of its ATP binding subunit, DNA gyrase B (GyrB), have so far not reached clinical use. In the present study, three different series of N-phenyl-4,5-dibromop-yrrolamides and N-phenylindolamides were designed and prepared as potential DNA gyrase B inhibitors. The IC50 values of compounds on DNA gyrase from Escherichia coli were in the low micromolar range, with the best compound, (4-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzoyl)glycine (18a), displaying an IC50 of 450 nM. For this compound, a high-resolution crystal structure in complex with E. coli DNA gyrase B was obtained, revealing details of its binding mode within the active site. The binding affinities. of three compounds with GyrB were additionally evaluated by surface plasmon resonance, and the results were in good agreement with the determined enzymatic activities. For the most promising compounds, the inhibitory activities against DNA gyrase from Staphylococcus aureus and topoisomerases IV from E. coli and S. aureus were determined. Antibacterial activities of the most potent compounds of each series were evaluated against two Gram-positive and two Gram-negative bacterial strains. The results obtained in this study provide valuable information on the binding mode and structure activity relationship of N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides as promising classes of ATP competitive GyrB inhibitors. IC50 =450 nM

  DOI：

  10.1021/acs.jmedchem.5b00775
• 作为产物：
  描述：

  3-氨基丙酸甲酯盐酸盐 、 4-硝基苯甲酰氯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 15.0h， 以74%的产率得到methyl 3-(4-nitrobenzamido)propanoate
  参考文献：
  名称：

  N-Phenyl-4,5-dibromopyrrolamides and N-Phenylindolamides as ATP Competitive DNA Gyrase B Inhibitors: Design, Synthesis, and Evaluation

  摘要：

  Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors of its ATP binding subunit, DNA gyrase B (GyrB), have so far not reached clinical use. In the present study, three different series of N-phenyl-4,5-dibromop-yrrolamides and N-phenylindolamides were designed and prepared as potential DNA gyrase B inhibitors. The IC50 values of compounds on DNA gyrase from Escherichia coli were in the low micromolar range, with the best compound, (4-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzoyl)glycine (18a), displaying an IC50 of 450 nM. For this compound, a high-resolution crystal structure in complex with E. coli DNA gyrase B was obtained, revealing details of its binding mode within the active site. The binding affinities. of three compounds with GyrB were additionally evaluated by surface plasmon resonance, and the results were in good agreement with the determined enzymatic activities. For the most promising compounds, the inhibitory activities against DNA gyrase from Staphylococcus aureus and topoisomerases IV from E. coli and S. aureus were determined. Antibacterial activities of the most potent compounds of each series were evaluated against two Gram-positive and two Gram-negative bacterial strains. The results obtained in this study provide valuable information on the binding mode and structure activity relationship of N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides as promising classes of ATP competitive GyrB inhibitors. IC50 =450 nM

  DOI：

  10.1021/acs.jmedchem.5b00775

文献信息

• Soil redox, pH, temperature, and water-table patterns of a freshwater tidal wetland
  作者：Cathy A. Seybold、Wondi Mersie、Jayie Huang、Clyde McNamee

  DOI：10.1672/0277-5212(2002)022[0149:srptaw]2.0.co;2

  日期：2002.3

  Knowledge of wetland hydrology, soil redox potential, pH, and temperature dynamics are key components required to understand the capacity of tidal wetlands to function, in particular to attenuate agrichemicals. In a freshwater tidal wetland along the James River in Virginia, USA, redox potential, pH, water-table level, and soil temperature were monitored continuously at two depths (20 and 50 cm) at three sites during a 12-month period from September 1, 1997 to August 31. 1998. Redox potentials were at or below - 150 mV (methanogenic or sulfate reducing conditions) at the 50-cm depth during the entire monitoring period. At the 20-cm depth. redox potentials remained highly reducing 95% of the time. The soil is continuously wet throughout the year, with the water-table level above the 20-cm soil depth for 95% of the time. Water-table level or hydrology was the primary factor controlling fluctuations in the redox state. Soil pH values were generally between 6 and 8, and they dropped I pH unit upon an oxidation event. which was reversible. Soil temperature at the 50-cm depth never dropped below 5degrees C, indicating a year-round biological activity season. This wetland supports a large diversity of plant species. Permanently reduced sub-surfaces, year-round biological activity, and large organic matter accumulations are characteristic features of this freshwater tidal wetland.
• <i>N</i>-Phenyl-4,5-dibromopyrrolamides and <i>N</i>-Phenylindolamides as ATP Competitive DNA Gyrase B Inhibitors: Design, Synthesis, and Evaluation
  作者：Nace Zidar、Helena Macut、Tihomir Tomašič、Matjaž Brvar、Sofia Montalvão、Päivi Tammela、Tom Solmajer、Lucija Peterlin Mašič、Janez Ilaš、Danijel Kikelj

  DOI：10.1021/acs.jmedchem.5b00775

  日期：2015.8.13

  Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors of its ATP binding subunit, DNA gyrase B (GyrB), have so far not reached clinical use. In the present study, three different series of N-phenyl-4,5-dibromop-yrrolamides and N-phenylindolamides were designed and prepared as potential DNA gyrase B inhibitors. The IC50 values of compounds on DNA gyrase from Escherichia coli were in the low micromolar range, with the best compound, (4-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzoyl)glycine (18a), displaying an IC50 of 450 nM. For this compound, a high-resolution crystal structure in complex with E. coli DNA gyrase B was obtained, revealing details of its binding mode within the active site. The binding affinities. of three compounds with GyrB were additionally evaluated by surface plasmon resonance, and the results were in good agreement with the determined enzymatic activities. For the most promising compounds, the inhibitory activities against DNA gyrase from Staphylococcus aureus and topoisomerases IV from E. coli and S. aureus were determined. Antibacterial activities of the most potent compounds of each series were evaluated against two Gram-positive and two Gram-negative bacterial strains. The results obtained in this study provide valuable information on the binding mode and structure activity relationship of N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides as promising classes of ATP competitive GyrB inhibitors. IC50 =450 nM