4-(5-chlorobenzo[d]oxazol-2-yl)butanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 4-(5-chlorobenzo[d]oxazol-2-yl)butanoic acid
• 英文别名: 4-(5-Chloro-1,3-benzoxazol-2-yl)butanoic acid
• 化学式: C₁₁H₁₀ClNO₃
• 分子量: 239.658
• InChiKey: GZMAFZUDDMYJEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 4-(5-chlorobenzo[d]oxazol-2-yl)butanoic acid 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以40%的产率得到4-(5-chlorobenzo[d]oxazol-2-yl)-1-(pyrrolidin-1-yl)butan-1-one
  参考文献：
  名称：

  MymA Bioactivated Thioalkylbenzoxazole Prodrug Family Active against Mycobacterium tuberculosis

  摘要：

  Screening of a GSK-proprietary library against intracellular Mycobacterium tuberculosis identified 1, a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.

  DOI：

  10.1021/acs.jmedchem.0c00003
• 作为产物：
  描述：

  戊二酸 、 4-氯-2-氨基苯酚 在 polyphosphoric acid 作用下， 以78%的产率得到4-(5-chlorobenzo[d]oxazol-2-yl)butanoic acid
  参考文献：
  名称：

  MymA Bioactivated Thioalkylbenzoxazole Prodrug Family Active against Mycobacterium tuberculosis

  摘要：

  Screening of a GSK-proprietary library against intracellular Mycobacterium tuberculosis identified 1, a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.

  DOI：

  10.1021/acs.jmedchem.0c00003

文献信息

• MymA Bioactivated Thioalkylbenzoxazole Prodrug Family Active against <i>Mycobacterium tuberculosis</i>
  作者：Abraham L. Moure、Gagandeep Narula、Flavia Sorrentino、Adama Bojang、Clement K. M. Tsui、Carine Sao Emani、Esther Porras-De Francisco、Beatriz Díaz、María José Rebollo-López、Pedro Alfonso Torres-Gómez、Eva María López-Román、Isabel Camino、Patricia Casado Castro、Laura Guijarro López、Fátima Ortega、Lluis Ballell、David Barros-Aguirre、Modesto Remuiñán Blanco、Yossef Av-Gay

  DOI：10.1021/acs.jmedchem.0c00003

  日期：2020.5.14

  Screening of a GSK-proprietary library against intracellular Mycobacterium tuberculosis identified 1, a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.