(6R,7R)-3-(acetoxymethyl)-7-(2-(4-bromophenyl)-acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (6R,7R)-3-(acetoxymethyl)-7-(2-(4-bromophenyl)-acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 英文别名: (6R,7R)-3-(acetyloxymethyl)-7-[[2-(4-bromophenyl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 化学式: C₁₈H₁₇BrN₂O₆S
• 分子量: 469.313
• InChiKey: MTJHUDNOFVMQSM-RHSMWYFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-溴苯乙酰氯 、 7-氨基头孢烷酸 在 苯胺 作用下， 以 乙酸乙酯 为溶剂， 反应 1.5h， 以76%的产率得到(6R,7R)-3-(acetoxymethyl)-7-(2-(4-bromophenyl)-acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

  摘要：

  Expression of beta-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to beta-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a beta-lactamase-cleavable motif. The prodrug is only bactericidal after activation by beta-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse beta-lactamases; bactericidal activity was not observed in strains without beta-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target beta-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce beta-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.

  DOI：

  10.1021/acs.jmedchem.8b01923

文献信息

• Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug
  作者：Lindsay E. Evans、Aishwarya Krishna、Yajing Ma、Thomas E. Webb、Dominic C. Marshall、Catherine L. Tooke、James Spencer、Thomas B. Clarke、Alan Armstrong、Andrew M. Edwards

  DOI：10.1021/acs.jmedchem.8b01923

  日期：2019.5.9

  Expression of beta-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to beta-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a beta-lactamase-cleavable motif. The prodrug is only bactericidal after activation by beta-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse beta-lactamases; bactericidal activity was not observed in strains without beta-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target beta-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce beta-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.