3-(3-(4-acetylphenyl)ureido)benzoic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(3-(4-acetylphenyl)ureido)benzoic acid
• 英文别名: 3-{[(4-Acetylphenyl)carbamoyl]amino}benzoic acid；3-[(4-acetylphenyl)carbamoylamino]benzoic acid
• 化学式: C₁₆H₁₄N₂O₄
• mdl: MFCD03229331
• 分子量: 298.298
• InChiKey: LACSCBVUVXZNOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-乙酰苯基异氰酸酯 、 间氨基苯甲酸 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以79%的产率得到3-(3-(4-acetylphenyl)ureido)benzoic acid
  参考文献：
  名称：

  Inhibitors of the Cysteine Synthase CysM with Antibacterial Potency against Dormant Mycobacterium tuberculosis

  摘要：

  Cysteine is an important amino acid in the redox defense of Mycobacterium tuberculosis, primarily as a building block of mycothiol. Genetic studies have implicated de novo cysteine biosynthesis in pathogen survival in infected macrophages, in particular for persistent M. tuberculosis. Here, we report on the identification and characterization of potent inhibitors of CysM, a critical enzyme in cysteine biosynthesis during dormancy. A screening campaign of 17?312 compounds identified ligands that bind to the active site with micromolar affinity. These were characterized in terms of their inhibitory potencies and structure-activity relationships through hit expansion guided by three-dimensional structures of enzyme-inhibitor complexes. The top compound binds to CysM with 300 nM affinity and displays selectivity over the mycobacterial homologues CysK1 and CysK2. Notably, two inhibitors show significant potency in a nutrient-starvation model of dormancy of Mycobacterium tuberculosis, with little or no cytotoxicity toward mammalian cells.

  DOI：

  10.1021/acs.jmedchem.6b00674

文献信息

• Inhibitors of the Cysteine Synthase CysM with Antibacterial Potency against Dormant <i>Mycobacterium tuberculosis</i>
  作者：Katharina Brunner、Selma Maric、Rudraraju Srilakshmi Reshma、Helena Almqvist、Brinton Seashore-Ludlow、Anna-Lena Gustavsson、Ömer Poyraz、Perumal Yogeeswari、Thomas Lundbäck、Michaela Vallin、Dharmarajan Sriram、Robert Schnell、Gunter Schneider

  DOI：10.1021/acs.jmedchem.6b00674

  日期：2016.7.28

  Cysteine is an important amino acid in the redox defense of Mycobacterium tuberculosis, primarily as a building block of mycothiol. Genetic studies have implicated de novo cysteine biosynthesis in pathogen survival in infected macrophages, in particular for persistent M. tuberculosis. Here, we report on the identification and characterization of potent inhibitors of CysM, a critical enzyme in cysteine biosynthesis during dormancy. A screening campaign of 17?312 compounds identified ligands that bind to the active site with micromolar affinity. These were characterized in terms of their inhibitory potencies and structure-activity relationships through hit expansion guided by three-dimensional structures of enzyme-inhibitor complexes. The top compound binds to CysM with 300 nM affinity and displays selectivity over the mycobacterial homologues CysK1 and CysK2. Notably, two inhibitors show significant potency in a nutrient-starvation model of dormancy of Mycobacterium tuberculosis, with little or no cytotoxicity toward mammalian cells.