2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2R,3S)-2-[[[5-hydroxy-1-(methylamino)-4-oxopyridine-2-carbonyl]amino]methyl]-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid | 1445727-99-0

• 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-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2R,3S)-2-[[[5-hydroxy-1-(methylamino)-4-oxopyridine-2-carbonyl]amino]methyl]-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
• CAS: 1445727-99-0
• 化学式: C₂₀H₂₄N₈O₁₁S₂
• 分子量: 616.59
• InChiKey: WHWKKNXMDBHSKP-SXZTXGLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  320
• 氢给体数：
  7
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  (3S,4S)-3-amino-4-(hydroxymethyl)azetidin-2-one acetic acid 在 咪唑 、 palladium 10% on activated carbon 、 碘 、 三氧化硫吡啶 、 叠氮化四丁基铵 、 三氯化硼 、 碳酸氢钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 乙醇 、 二氯甲烷 、 对二甲苯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~35.0 ℃ 、206.85 kPa 条件下， 反应 36.08h， 生成 2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2R,3S)-2-[[[5-hydroxy-1-(methylamino)-4-oxopyridine-2-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

• 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.