(6R,7R)-3-(acetoxymethyl)-7-butyramido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 7629-66-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (6R,7R)-3-(acetoxymethyl)-7-butyramido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 英文别名: (6R,7R)-3-(acetyloxymethyl)-7-(butanoylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 7629-66-5
• 化学式: C₁₄H₁₈N₂O₆S
• 分子量: 342.373
• InChiKey: DJLOKMQBWZXCBH-ZWNOBZJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 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：

  丁酰氯 、 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12%的产率得到(6R,7R)-3-(acetoxymethyl)-7-butyramido-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

• Processes using amino acid dehydrogenases and ketoreductase-based cofactor regenerating system
  申请人：Codexis, Inc.

  公开号：US10196667B2

  公开（公告）日：2019-02-05

  The present disclosure relates to the use of an amino acid dehydrogenase in combination with a cofactor regenerating system comprising a ketoreductase. In particular embodiments, the process can be used to prepare L-tert-leucine using a leucine dehydrogenase.

  本公开涉及将氨基酸脱氢酶与由酮还原酶组成的辅助因子再生系统结合使用。在具体的实施方案中，该工艺可用于使用亮氨酸脱氢酶制备 L-叔亮氨酸。
• Kinetic resolutions of racemic amines and alcohols catalyzed by an industrial glutaryl-7-aminocephalosporanic acid acylase with unexpected broad substrate specificity
  作者：Stefano Raimondi、Luca Forti、Daniela Monti、Sergio Riva

  DOI：10.1016/s0957-4166(03)00171-x

  日期：2003.5

  An industrial glutaryl-7-aminocephalosporanic acid acylase (GAR) possesses a significant broad substrate specificity that crosses over the usual cephalosporanic skeleton. Enantioselective amidase and even esterase activities have been observed with all the glutarates of racemic substrates investigated, with a stereopreference for the (S)-enantiomer. The different physical-chemical properties of reagents and products allow their easy separation by solvent extraction, avoiding cumbersome chromatography or distillation processes during reaction work-up. (C) 2003 Elsevier Science Ltd. All rights reserved.
• PROCESSES USING AMINO ACID DEHYDROGENASES AND KETOREDUCTASE-BASED COFACTOR REGENERATING SYSTEM
  申请人：Codexis, Inc.

  公开号：US20170292141A1

  公开（公告）日：2017-10-12

  The present disclosure relates to the use of an amino acid dehydrogenase in combination with a cofactor regenerating system comprising a ketoreductase. In particular embodiments, the process can be used to prepare L-tert-leucine using a leucine dehydrogenase.
• US9714439B2
  申请人：——

  公开号：US9714439B2

  公开（公告）日：2017-07-25
• 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.