(2S,5R)-6-hydroxy-7-oxo-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)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile
• 英文别名: (2S,5R)-6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonitrile
• 化学式: C₇H₉N₃O₂
• 分子量: 167.167
• InChiKey: BHTQJWJCSYUVSD-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile 在 三氧化硫 N,N-二甲基甲酰胺络合物 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 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：

  (2S,5R)-5-((benzyloxy)amino)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid 在 palladium 10% on activated carbon 、 氨 、 氢气 、 三乙胺 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -40.0~30.0 ℃ 、300.01 kPa 条件下， 反应 31.5h， 生成 (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile
  参考文献：
  名称：

  [EN] NITROGEN CONTAINING COMPOUNDS AND THEIR USE
  [FR] COMPOSÉS AZOTÉS ET LEUR UTILISATION

  摘要：

  公式（I）的化合物，其制备和在预防或治疗细菌感染中的用途被披露。

  公开号：

  WO2013038330A1

文献信息

• [EN] 2-CYANOPYRROLDINES, -PIPERIDINES OR -DAZEPINES AS HYPERGLYCEMIC AGENTS<br/>[FR] 2-CYANO-PYRROLIDINES, -PIPÉRIDINES OU -DIAZÉPINES UTILISÉES COMME AGENTS HYPERGLYCÉMIQUES
  申请人：WOCKHARDT BIO AG

  公开号：WO2021165927A1

  公开（公告）日：2021-08-26

  Nitrogen containing compounds of Formula (I), pharmaceutical compositions comprising these compounds and their use in treating hypoglycaemia is disclosed.

  Formula (I)中含氮化合物的药物组合物及其在治疗低血糖中的应用被揭示。
• [EN] NOVEL HETEROCYCLIC COMPOUNDS AND THEIR USE IN PREVENTING OR TREATING BACTERIAL INFECTIONS<br/>[FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION POUR PRÉVENIR OU TRAITER DES INFECTIONS BACTÉRIENNES
  申请人：MUTABILIS

  公开号：WO2018141991A1

  公开（公告）日：2018-08-09

  The present invention relates to compound of formula (I) and their use for treating bacterial infections.

  本发明涉及化合物的公式（I）以及它们用于治疗细菌感染的用途。
• [EN] BETA-LACTAMASE INHIBITORS AND THEIR PREPARATION<br/>[FR] INHIBITEURS DE BÊTA-LACTAMASE ET LEUR PRÉPARATION
  申请人：NINGXIA ACADEMY AGRICULTURE & FORESTRY SCIENCES

  公开号：WO2022047603A1

  公开（公告）日：2022-03-10

  Provided herein are novel β-lactamase inhibitors, for the treatment of bacterial infections in combination with β-lactam antibiotics, including infection caused by drug resistant organisms and especially multi-drug resistant organisms. It includes compounds according to formula (I): or pharmaceutically acceptable salts thereof, wherein M and R are as defined herein.

  本文提供了一种新型的β-内酰胺酶抑制剂，用于与β-内酰胺类抗生素结合治疗细菌感染，包括由耐药性细菌引起的感染，尤其是多重耐药性细菌。它包括按照以下公式（I）的化合物或其药用盐，其中M和R如本文所定义。
• β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes
  作者：Zafar Iqbal、Lijuan Zhai、Yuanyu Gao、Dong Tang、Xueqin Ma、Jinbo Ji、Jian Sun、Jingwen Ji、Yuanbai Liu、Rui Jiang、Yangxiu Mu、Lili He、Haikang Yang、Zhixiang Yang

  DOI：10.3762/bjoc.17.60

  日期：——

  The diazabicyclooctane (DBO) scaffold is the backbone of non-β-lactam-based second generation β-lactamase inhibitors. As part of our efforts, we have synthesized a series of DBO derivatives A1–23 containing amidine substituents at the C2 position of the bicyclic ring. These compounds, alone and in combination with meropenem, were tested against ten bacterial strains for their antibacterial activity in vitro. All compounds did not show antibacterial activity when tested alone (MIC >64 mg/L), however, they exhibited a moderate inhibition activity in the presence of meropenem by lowering its MIC values. The compound A12 proved most potent among the other counterparts against all bacterial species with MIC from <0.125 mg/L to 2 mg/L, and is comparable to avibactam against both E. coli strains with a MIC value of <0.125 mg/L.

  重氮双环辛烷（DBO）支架是非β-内酰胺类第二代β-内酰胺酶抑制剂的骨架。作为研究工作的一部分，我们合成了一系列 DBO 衍生物 A1-23，这些衍生物在双环的 C2 位含有脒取代基。这些化合物单独或与美罗培南复配，针对十种细菌菌株进行了体外抗菌活性测试。所有化合物在单独测试时均未显示出抗菌活性（MIC 为 64 毫克/升），但在美罗培南存在的情况下，它们显示出适度的抑制活性，降低了美罗培南的 MIC 值。事实证明，化合物 A12 对所有细菌种类都具有最强的抗菌活性，其 MIC 值为 0.125 mg/L 至 2 mg/L，对两种大肠杆菌菌株的 MIC 值均为 0.125 mg/L，与阿维菌素相当。
• [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。