(2S,5R)-6-benzyloxy-7-oxo-2-[((3R)-N-Boc-pyrrolidine-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]octane | 1436862-03-1

• 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: (2S,5R)-6-benzyloxy-7-oxo-2-[((3R)-N-Boc-pyrrolidine-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]octane
• 英文别名: (2S,5R)-6-benzyloxy-7-oxo-2-[((3R)-N-Boc-pyrrolidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo[3.2.1]octane；tert-butyl (3R)-3-[[[(2S,5R)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1436862-03-1
• 化学式: C₂₄H₃₃N₅O₆
• 分子量: 487.556
• InChiKey: ZISOVUPMUBKDOC-QRVBRYPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,5R)-6-benzyloxy-7-oxo-2-[((3R)-N-Boc-pyrrolidine-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]octane 在 palladium 10% on activated carbon 、 氢气 、 三氧化硫吡啶 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 3-[N'-(6-sulfooxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl)hydrazinocarbonyl]-(R)-pyrrolidine-1-carboxylic acid tert-butyl ester tetrabutylammonium 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：

  R-1-CBZ-3-哌啶甲醇 在 盐酸 、 Jones reagent 、 hydrazine hydrate 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 80.0 ℃ 、689.49 kPa 条件下， 反应 25.0h， 生成 (2S,5R)-6-benzyloxy-7-oxo-2-[((3R)-N-Boc-pyrrolidine-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]octane
  参考文献：
  名称：

  [EN] A PROCESS FOR PREPARATION OF (2S, 5R)-7-OXO-6-SULPHOOXY-2-[((3R)-PYRROLIDINE-3-CARBONYL)-HYDRAZINO CARBONYL]-1,6-DIAZA-BICYCLO[3.2.1]OCTANE
  [FR] PROCÉDÉ DE PRÉPARATION DE (2S, 5R)-7-OXO-6-SULFOXY-2-[((3R)- PYRROLIDINE- 3-CARBONYL)-HYDRAZINOCARBONYL]-1,6-DIAZA-BICYCLO[3.2.1]OCTANE

  摘要：

  揭示了一种制备(2S, 5R)-7-氧代-6-磺氧基-2- [((3R)-吡咯烷-3-羰基)-肼羰基]-1,6-二氮杂-双环[3.2.1]辛烷的方法，包括将式(II)的化合物与式(III)的化合物反应以获得式(IV)的化合物。还声称了结晶的终产物。

  公开号：

  WO2014135932A1

文献信息

• A process for preparation of (2S, 5R)-7-oxo-6-sulphooxy-2-[((3R)-pyrrolidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo[3.2.1]octane
  申请人：WOCKHARDT LIMITED

  公开号：US20160002234A1

  公开（公告）日：2016-01-07

  A process for preparation of (2S,5R)-7-oxo-6-sulphooxy-2-[((3R)-pyrrolidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo[3.2.1]octane is disclosed comprising reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV). The crystalline end-product is als claimed.

  本发明公开了一种制备(2S,5R)-7-氧代-6-磺酸氧基-2-[((3R)-吡咯烷-3-羧酰基)-肼羧酰基]-1,6-二氮杂双环[3.2.1]辛烷的方法，包括将式（II）的化合物与式（III）的化合物反应以获得式（IV）的化合物。本发明还声明了所得到的结晶性终产物。
• [EN] 1,3,4-OXADIAZOLE AND 1,3,4-THIADIAZOLE &bgr;-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE LA 1,3,4-OXADIAZOLE ET DE LA 1,3,4-THIADIAZOLE BÊTA-LACTAMASE
  申请人：CUBIST PHARM INC

  公开号：WO2013149121A8

  公开（公告）日：2014-05-01
• US9624222B2
  申请人：——

  公开号：US9624222B2

  公开（公告）日：2017-04-18
• 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
  作者：Krisztina M. Papp-Wallace、Nhu Q. Nguyen、Michael R. Jacobs、Christopher R. Bethel、Melissa D. Barnes、Vijay Kumar、Saralee Bajaksouzian、Susan D. Rudin、Philip N. Rather、Satish Bhavsar、Tadiparthi Ravikumar、Prasad K. Deshpande、Vijay Patil、Ravindra Yeole、Sachin S. Bhagwat、Mahesh V. Patel、Focco van den Akker、Robert A. Bonomo

  DOI：10.1021/acs.jmedchem.8b00091

  日期：2018.5.10

  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.
• [EN] A PROCESS FOR PREPARATION OF (2S, 5R)-7-OXO-6-SULPHOOXY-2-[((3R)-PYRROLIDINE-3-CARBONYL)-HYDRAZINO CARBONYL]-1,6-DIAZA-BICYCLO[3.2.1]OCTANE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE (2S, 5R)-7-OXO-6-SULFOXY-2-[((3R)- PYRROLIDINE- 3-CARBONYL)-HYDRAZINOCARBONYL]-1,6-DIAZA-BICYCLO[3.2.1]OCTANE
  申请人：WOCKHARDT LTD

  公开号：WO2014135932A1

  公开（公告）日：2014-09-12

  A process for preparation of (2S, 5R)-7-oxo-6-sulphooxy-2- [((3R)-pyrrolidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza- bicyclo[3.2.1]octane is disclosed comprising reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV). The crystalline end-product is als claimed.

  揭示了一种制备(2S, 5R)-7-氧代-6-磺氧基-2- [((3R)-吡咯烷-3-羰基)-肼羰基]-1,6-二氮杂-双环[3.2.1]辛烷的方法，包括将式(II)的化合物与式(III)的化合物反应以获得式(IV)的化合物。还声称了结晶的终产物。