2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-({(2R,3S)-2-[({[3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)isoxazol-5-yl]carbonyl}amino)methyl]-4-oxo-1-sulfoazetidin-3-yl}amino)-2-oxoethylidene]amino}oxy)-2-methylpropanoic acid | 1380110-66-6

• 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: 2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-({(2R,3S)-2-[({[3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)isoxazol-5-yl]carbonyl}amino)methyl]-4-oxo-1-sulfoazetidin-3-yl}amino)-2-oxoethylidene]amino}oxy)-2-methylpropanoic acid
• 英文别名: 2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2R,3S)-2-[[[3-(1,5-dihydroxy-4-oxopyridin-2-yl)-1,2-oxazole-5-carbonyl]amino]methyl]-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
• CAS: 1380110-66-6
• 化学式: C₂₂H₂₂N₈O₁₃S₂
• 分子量: 670.594
• InChiKey: PSCYIVJNYTWLTK-LWGJOKMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  354
• 氢给体数：
  7
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-({(2R,3S)-2-[({[3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)isoxazol-5-yl]carbonyl}amino)methyl]-4-oxo-1-sulfoazetidin-3-yl}amino)-2-oxoethylidene]amino}oxy)-2-methylpropanoic acid 在 碳酸氢钠 作用下， 以 水 为溶剂， 以97%的产率得到2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-({(2R,3S)-2-[({[3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)isoxazol-5-yl]carbonyl}amino)methyl]-4-oxo-1-sulfoazetidin-3-yl}amino)-2-oxoethylidene]amino}oxy)-2-methylpropanoic acid bis sodium salt
  参考文献：
  名称：

  [EN] MONOBACTAMS
  [FR] MONOBACTAMES

  摘要：

  本发明涉及一类新的单环内酰胺衍生物及其用于治疗细菌感染的用途。

  公开号：

  WO2012073138A1
• 作为产物：
  描述：

  4,5-二苄氧基吡啶甲酸苄酯 在 吡啶 、 sodium tetrahydroborate 、 N-氯代丁二酰亚胺 、 三氧化硫 N,N-二甲基甲酰胺络合物 、 盐酸羟胺 、 sodium acetate 、 三氯化硼 、 碳酸氢钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 间氯过氧苯甲酸 、 lithium hydroxide 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.08h， 生成 2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-({(2R,3S)-2-[({[3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)isoxazol-5-yl]carbonyl}amino)methyl]-4-oxo-1-sulfoazetidin-3-yl}amino)-2-oxoethylidene]amino}oxy)-2-methylpropanoic acid
  参考文献：
  名称：

  Pyridone-Conjugated Monobactam Antibiotics with Gram-Negative Activity

  摘要：

  Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monohactam analogues with in vitro, antibacterial activity against clinically relevant Grain-negative species including Pseuedomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Rat pharmacokinetic studies with,compound 17 demonstrate low clearance and low plasma protein binding. In addition evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.

  DOI：

  10.1021/jm400560z

文献信息

• MONOBACTAMS
  申请人：Pfizer Inc.

  公开号：EP2646436B1

  公开（公告）日：2015-05-27
• Monobactams
  申请人：PFIZER INC.

  公开号：US20130252935A1

  公开（公告）日：2013-09-26

  The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections.
• MONOCYCLIC BETA-LACTAM-SIDEROPHORE CONJUGATE, AND PREPARATION METHOD AND USE THEREOF
  申请人：Yang Yushe

  公开号：US20190233407A1

  公开（公告）日：2019-08-01

  The present disclosure relates to the field of pharmaceutical synthesis, and more particularly, relates to a monocyclic β-lactam-siderophore conjugate as well as a method for synthesizing same and its use in the treatment of bacterial infectious diseases. Provided are a monocyclic β-lactam-siderophore conjugate represented by formula (I) as described herein, an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a method for synthesizing same, and a use thereof in treating bacterial infectious diseases.
• [EN] MONOBACTAMS<br/>[FR] MONOBACTAMES
  申请人：PFIZER

  公开号：WO2012073138A1

  公开（公告）日：2012-06-07

  The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections.

  本发明涉及一类新的单环内酰胺衍生物及其用于治疗细菌感染的用途。
• Pyridone-Conjugated Monobactam Antibiotics with Gram-Negative Activity
  作者：Matthew F. Brown、Mark J. Mitton-Fry、Joel T. Arcari、Rose Barham、Jeffrey Casavant、Brian S. Gerstenberger、Seungil Han、Joel R. Hardink、Thomas M. Harris、Thuy Hoang、Michael D. Huband、Manjinder S. Lall、M. Megan Lemmon、Chao Li、Jian Lin、Sandra P. McCurdy、Eric McElroy、Craig McPherson、Eric S. Marr、John P. Mueller、Lisa Mullins、Antonia A. Nikitenko、Mark C. Noe、Joseph Penzien、Mark S. Plummer、Brandon P. Schuff、Veerabahu Shanmugasundaram、Jeremy T. Starr、Jianmin Sun、Andrew Tomaras、Jennifer A. Young、Richard P. Zaniewski

  DOI：10.1021/jm400560z

  日期：2013.7.11

  Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monohactam analogues with in vitro, antibacterial activity against clinically relevant Grain-negative species including Pseuedomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Rat pharmacokinetic studies with,compound 17 demonstrate low clearance and low plasma protein binding. In addition evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.