4-(4'-hydroxy-3-biphenyl)-5-phenylisoxazole-3-carboxylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 4-(4'-hydroxy-3-biphenyl)-5-phenylisoxazole-3-carboxylic acid
• 英文别名: 4-[3-(4-Hydroxyphenyl)phenyl]-5-phenyl-1,2-oxazole-3-carboxylic acid；4-[3-(4-hydroxyphenyl)phenyl]-5-phenyl-1,2-oxazole-3-carboxylic acid
• 化学式: C₂₂H₁₅NO₄
• 分子量: 357.365
• InChiKey: QSBOZQWNPQOIPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二氧代-4-苯丁酸甲酯 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 盐酸羟胺 、 sodium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 反应 79.0h， 生成 4-(4'-hydroxy-3-biphenyl)-5-phenylisoxazole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo

  摘要：

  Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.

  DOI：

  10.1021/acs.jmedchem.8b00832

文献信息

• Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Survival and Infection Burden in Vivo
  作者：Clare F. Vickers、Ana P. G. Silva、Ajanta Chakraborty、Paulina Fernandez、Natalia Kurepina、Charis Saville、Yandi Naranjo、Miquel Pons、Laura S. Schnettger、Maximiliano G. Gutierrez、Steven Park、Barry N. Kreiswith、David S. Perlin、Eric J. Thomas、Jennifer S. Cavet、Lydia Tabernero

  DOI：10.1021/acs.jmedchem.8b00832

  日期：2018.9.27

  Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.