2-((4-amino-5-(3-nitrophenyl)-4H-1,2,4-triazol-3-yl)thio)-N-(benzoxazol-2-yl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-((4-amino-5-(3-nitrophenyl)-4H-1,2,4-triazol-3-yl)thio)-N-(benzoxazol-2-yl)acetamide
• 化学式: C₁₇H₁₃N₇O₄S
• 分子量: 411.401
• InChiKey: JWSSLLWKBDHEKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  155.0
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  2-氨基苯并噁唑 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 2-((4-amino-5-(3-nitrophenyl)-4H-1,2,4-triazol-3-yl)thio)-N-(benzoxazol-2-yl)acetamide
  参考文献：
  名称：

  Azolylthioacetamides as a potent scaffold for the development of metallo-β-lactamase inhibitors

  摘要：

  In an effort to develop new inhibitors of metallo-beta-lactamases (MbLs), twenty-eight azolylthioacetamides were synthesized and assayed against MbLs. The obtained benzimidazolyl and benzioxazolyl substituted 1-19 specifically inhibited the enzyme ImiS, and 10 was found to be the most potent inhibitor of ImiS with an IC50 value of 15 nM. The nitrobenzimidazolyl substituted 20-28 specifically inhibited NDM-1, with 27 being the most potent inhibitor with an IC50 value of 170 nM. Further studies with 10, 11, and 27 revealed a mixed inhibition mode with competitive and uncompetitive inhibition constants in a similar range as the IC50 values. These inhibitors resulted in a 2-4-fold decrease in imipenem MIC values using E. coli cells producing ImiS or NDM-1. While the source of uncompetitive (possibly allosteric) inhibition remains unclear, docking studies indicate that 10 and 11 may interact orthosterically with Zn2 in the active site of CphA, while 27 could bridge the two Zn(II) ions in the active site of NDM-1 via its nitro group. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.038

文献信息

• Azolylthioacetamides as a potent scaffold for the development of metallo-β-lactamase inhibitors
  作者：Yang Xiang、Ya-Nan Chang、Ying Ge、Joon S. Kang、Yi-Lin Zhang、Xiao-Long Liu、Peter Oelschlaeger、Ke-Wu Yang

  DOI：10.1016/j.bmcl.2017.10.038

  日期：2017.12

  In an effort to develop new inhibitors of metallo-beta-lactamases (MbLs), twenty-eight azolylthioacetamides were synthesized and assayed against MbLs. The obtained benzimidazolyl and benzioxazolyl substituted 1-19 specifically inhibited the enzyme ImiS, and 10 was found to be the most potent inhibitor of ImiS with an IC50 value of 15 nM. The nitrobenzimidazolyl substituted 20-28 specifically inhibited NDM-1, with 27 being the most potent inhibitor with an IC50 value of 170 nM. Further studies with 10, 11, and 27 revealed a mixed inhibition mode with competitive and uncompetitive inhibition constants in a similar range as the IC50 values. These inhibitors resulted in a 2-4-fold decrease in imipenem MIC values using E. coli cells producing ImiS or NDM-1. While the source of uncompetitive (possibly allosteric) inhibition remains unclear, docking studies indicate that 10 and 11 may interact orthosterically with Zn2 in the active site of CphA, while 27 could bridge the two Zn(II) ions in the active site of NDM-1 via its nitro group. (C) 2017 Elsevier Ltd. All rights reserved.