trans-3-[(Z)-2-(2-aminothiazol-4-yl)-2-[[4-[[2-(4-hydroxybenzylidene)hydrazino]carbonyl]benzyloxy]imino]acetamido]-4-methyl-2-oxoazetidine-1-sulfonic acid triethylammonium salt

• 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: trans-3-[(Z)-2-(2-aminothiazol-4-yl)-2-[[4-[[2-(4-hydroxybenzylidene)hydrazino]carbonyl]benzyloxy]imino]acetamido]-4-methyl-2-oxoazetidine-1-sulfonic acid triethylammonium salt
• 英文别名: (2S,3S)-3-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[[4-[[(E)-(2-hydroxyphenyl)methylideneamino]carbamoyl]phenyl]methoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid;N,N-diethylethanamine
• 化学式: C₆H₁₅N*C₂₄H₂₃N₇O₈S₂
• 分子量: 702.813
• InChiKey: TWFRSBCZPQQOHU-JREVVAEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  266
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  4-[[2-(tert-butoxycarbonyl)hydrazino]carbonyl]benzyl chloride 在 4-二甲氨基吡啶 、 sodium hydroxide 、 potassium carbonate 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 sodium iodide 、 肼 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.25h， 生成 trans-3-[(Z)-2-(2-aminothiazol-4-yl)-2-[[4-[[2-(4-hydroxybenzylidene)hydrazino]carbonyl]benzyloxy]imino]acetamido]-4-methyl-2-oxoazetidine-1-sulfonic acid triethylammonium salt
  参考文献：
  名称：

  Antimicrobial effects of novel siderophores linked to β-lactam antibiotics

  摘要：

  As a strategy to increase the penetration of antibiotic drugs through the outer membrane of Gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-P-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities, suggesting that multiple factors influenced the intracellular concentration of the drugs. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00261-8

文献信息

• Antimicrobial effects of novel siderophores linked to β-lactam antibiotics
  作者：T Kline、M Fromhold、T.E McKennon、S Cai、J Treiberg、N Ihle、D Sherman、W Schwan、M.J Hickey、P Warrener、P.R Witte、L.L Brody、L Goltry、L.M Barker、S.U Anderson、S.K Tanaka、R.M Shawar、L.Y Nguyen、M Langhorne、A Bigelow、L Embuscado、E Naeemi

  DOI：10.1016/s0968-0896(99)00261-8

  日期：2000.1

  As a strategy to increase the penetration of antibiotic drugs through the outer membrane of Gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-P-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities, suggesting that multiple factors influenced the intracellular concentration of the drugs. (C) 2000 Elsevier Science Ltd. All rights reserved.