methyl 3-(3-phenylpropanoyl)-2,3-dihydro-2-thioxobenzo[d]oxazole-5-carboxylate | 1357026-04-0

• 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: methyl 3-(3-phenylpropanoyl)-2,3-dihydro-2-thioxobenzo[d]oxazole-5-carboxylate
• 英文别名: Methyl 3-(3-phenylpropanoyl)-2-sulfanylidene-1,3-benzoxazole-5-carboxylate
• CAS: 1357026-04-0
• 化学式: C₁₈H₁₅NO₄S
• 分子量: 341.387
• InChiKey: HFKVXJZVDCACGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  87.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基-4-羟基苯甲酸甲酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 methyl 3-(3-phenylpropanoyl)-2,3-dihydro-2-thioxobenzo[d]oxazole-5-carboxylate
  参考文献：
  名称：

  Design of benzimidazole- and benzoxazole-2-thione derivatives as inhibitors of bacterial hyaluronan lyase

  摘要：

  Bacterial hyaluronan lyases (Hyal) degrade hyaluronan, an important component of the extracellular matrix, and are involved in microbial spread. Hyal inhibitors may serve as tools to study the role of the enzyme, its substrates and products in the course of bacterial infections. Moreover, such enzyme inhibitors are potential candidates for antibacterial combination therapy. Based on crystal structures of Streptococcus pneumoniae Hyal in complex with a hexasaccharide substrate and with different inhibitors, 1-acylated benzimidazole-2-thiones and benzoxazole-2-thiones were derived as new leads for the inhibition of Streptococcus agalactiae strain 4755 Hyal. Structure-based optimization led to N-(3-phenylpropionyl)benzoxazole-2-thione, one of the most potent compounds known to date (IC50 values: 24 mu M at pH 7.4, 15 mu M at pH 5). Among the 27 new derivatives, other N-acylated benzimidazoles and benzoxazoles are just as active at pH 7.4, but not at pH 5. The results support a binding mode characterized by interactions with residues in the catalytic site and with a hydrophobic patch. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.07.014

文献信息

• Design of benzimidazole- and benzoxazole-2-thione derivatives as inhibitors of bacterial hyaluronan lyase
  作者：Stephan Braun、Alexander Botzki、Sunnhild Salmen、Christian Textor、Günther Bernhardt、Stefan Dove、Armin Buschauer

  DOI：10.1016/j.ejmech.2011.07.014

  日期：2011.9

  Bacterial hyaluronan lyases (Hyal) degrade hyaluronan, an important component of the extracellular matrix, and are involved in microbial spread. Hyal inhibitors may serve as tools to study the role of the enzyme, its substrates and products in the course of bacterial infections. Moreover, such enzyme inhibitors are potential candidates for antibacterial combination therapy. Based on crystal structures of Streptococcus pneumoniae Hyal in complex with a hexasaccharide substrate and with different inhibitors, 1-acylated benzimidazole-2-thiones and benzoxazole-2-thiones were derived as new leads for the inhibition of Streptococcus agalactiae strain 4755 Hyal. Structure-based optimization led to N-(3-phenylpropionyl)benzoxazole-2-thione, one of the most potent compounds known to date (IC50 values: 24 mu M at pH 7.4, 15 mu M at pH 5). Among the 27 new derivatives, other N-acylated benzimidazoles and benzoxazoles are just as active at pH 7.4, but not at pH 5. The results support a binding mode characterized by interactions with residues in the catalytic site and with a hydrophobic patch. (C) 2011 Elsevier Masson SAS. All rights reserved.