(2S,5R)-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 英文名称: (2S,5R)-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile
• 英文别名: trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile；[(2S,5R)-2-cyano-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl] hydrogen sulfate
• 化学式: C₇H₉N₃O₅S
• 分子量: 247.232
• InChiKey: JQDYTHSKUVKCRO-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,5R)-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile 在 indion 225 Na resin 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 trans-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]-octane-2-carbonitrile sodium salt
  参考文献：
  名称：

  Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using β-Lactamase Inhibitors and β-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234

  摘要：

  Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum beta-lactamases. The design of novel beta-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D beta-lactamases with unprecedented k2/K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C beta-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable aryl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel fi-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.

  DOI：

  10.1021/acs.jmedchem.8b00091
• 作为产物：
  描述：

  (1R,2S,5R)-7-氧代-6-(苄氧基)-1,6-二氮杂双环[3.2.1]辛烷-2-甲酰胺 在 三氧化硫 N,N-二甲基甲酰胺络合物 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -5.0~25.0 ℃ 、379.22 kPa 条件下， 反应 5.0h， 生成 (2S,5R)-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile
  参考文献：
  名称：

  Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using β-Lactamase Inhibitors and β-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234

  摘要：

  Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum beta-lactamases. The design of novel beta-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D beta-lactamases with unprecedented k2/K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C beta-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable aryl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel fi-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.

  DOI：

  10.1021/acs.jmedchem.8b00091

文献信息

• [EN] A PROCESS FOR PREPARATION OF (2S, 5R)-1,6-DIAZA-BICYCLO [3.2.1]OCTANE-2-CARBONITRILE-7-OXO-6-(SULFOOXY)-MONO SODIUM SALT<br/>[FR] PROCÉDÉ DE PRÉPARATION DE SEL DE SODIUM DE (2S, 5R)-7-OXO-6-(SULFOOXY)-1,6-DIAZA-BICYCLO[3.2.1]OCTANE-2-CARBONITRILE
  申请人：WOCKHARDT LTD

  公开号：WO2015114595A1

  公开（公告）日：2015-08-06

  A process for preparation of a compound of Formula (I) is disclosed.

  公开了一种制备化合物（I）的方法。
• NITROGEN CONTAINING COMPOUNDS AND THEIR USE
  申请人：Patil Vijaykumar Jagdishwar

  公开号：US20140088070A1

  公开（公告）日：2014-03-27

  Compounds of Formula (I), their preparation and use in preventing or treating bacterial infections are disclosed.

  公式（I）的化合物、它们的制备以及在预防或治疗细菌感染中的应用被披露。
• PHARMACEUTICAL COMPOSITIONS COMPRISING ANTIBACTERIAL AGENTS
  申请人：Wockhardt Limited

  公开号：EP3060208B1

  公开（公告）日：2018-09-19
• PHARMACEUTICAL COMBINATIONS COMPRISING ANTIBACTERIAL AGENTS
  申请人：WOCKHARDT LIMITED

  公开号：US20170065566A1

  公开（公告）日：2017-03-09

  Pharmaceutical compositions comprising antibacterial agents selected from cefepime, cefpirome or a pharmaceutically acceptable derivative thereof, and compound of Formula (I) or a stereoisomer or a pharmaceutical acceptable derivative thereof, are disclosed.
• CHEMICAL COMPOUNDS
  申请人：Antabio SAS

  公开号：US20200339526A1

  公开（公告）日：2020-10-29

  The invention relates to a compound which is a thiazole derivative of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Formula (A), Z, L, X, m, n and p are as defined herein. The compounds are useful in the treatment and prevention of bacterial infection. The invention also relates to combinations of the compound of Formula (I) with further active agents.