2-(((Z)-(1-(2-aminothiazol-4-yl)-2-(((2S,3S)-1-(((3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)-4-(2-(methylsulfonyl)ethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)sulfonyl)carbamoyl)-2-methyl-4-oxoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid

• 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-aminothiazol-4-yl)-2-(((2S,3S)-1-(((3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)-4-(2-(methylsulfonyl)ethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)sulfonyl)carbamoyl)-2-methyl-4-oxoazetidin-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-[[(2S,3S)-1-[[3-(1,5-dihydroxy-4-oxopyridin-2-yl)-4-(2-methylsulfonylethyl)-5-oxo-1,2,4-triazol-1-yl]sulfonylcarbamoyl]-2-methyl-4-oxoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
• 化学式: C₂₄H₂₈N₁₀O₁₄S₃
• 分子量: 776.743
• InChiKey: AFNTYFUFKUQFOW-ZOTZNXGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  51
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  386
• 氢给体数：
  6
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  5-[4,5-双(苯甲氧基)-2-吡啶基]-1,3,4-恶二唑-2(3H)-酮 在 氢气 、 钯 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 11.0h， 生成 2-(((Z)-(1-(2-aminothiazol-4-yl)-2-(((2S,3S)-1-(((3-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)-4-(2-(methylsulfonyl)ethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)sulfonyl)carbamoyl)-2-methyl-4-oxoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid
  参考文献：
  名称：

  SAR and Structural Analysis of Siderophore-Conjugated Monocarbam Inhibitors of Pseudomonas aeruginosa PBP3

  摘要：

  A main challenge in the development of new agents for the treatment of Pseudomonas aeruginosa infections is the identification of chemotypes that efficiently penetrate the cell envelope and are not susceptible to established resistance mechanisms. Siderophore-conjugated monocarbams are attractive because of their ability to hijack the bacteria's iron uptake machinery for transport into the periplasm and their inherent stability to metallo-beta-lactamases. Through development of the SAR we identified a number of modifications to the scaffold that afforded active anti-P. aeruginosa agents with good physicochemical properties. Through crystallographic efforts we gained a better understanding into how these compounds bind to the target penicillin binding protein PBP3 and factors to consider for future design.

  DOI：

  10.1021/acsmedchemlett.5b00026