(6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-3-[[(4-pyridyl)thio]methyl]-8-oxo-1-aza-5-thiabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 263153-97-5

• 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: (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-3-[[(4-pyridyl)thio]methyl]-8-oxo-1-aza-5-thiabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 263153-97-5
• 化学式: C₂₂H₂₂N₆O₇S₃
• 分子量: 578.651
• InChiKey: SPTPCESQRQIVMJ-LOBWNANLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.24
• 重原子数：
  38.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  197.4
• 氢给体数：
  4.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  5-Benzhydryloxy-2-chloromethyl-1H-pyridin-4-one 、 (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-3-[[(4-pyridyl)thio]methyl]-8-oxo-1-aza-5-thiabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 在 苯磺酰胺 、 三氟乙酸 、 sodium iodide 作用下， 生成 (6R,7R)-7-{2-(2-aminothiazol-4-yl)-2-[(Z)-(1-carboxy-1-methylethoxy)imino]acetamido}-3-({[1-(5-hydroxy-4-pyridon-2-yl)methylpyridinium-4-yl]thio}methyl)-8-oxo-1-aza-5-thiabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  头孢菌素，2-异烯和2-氧杂异烯与C-3'或C-7邻苯二酚或相关芳香族化合物的合成及构效关系。

  摘要：

  制备了一系列具有C-3'邻苯二酚的（4-吡啶鎓吡啶）甲基的头孢菌素，2-isophephems和2-oxaisocephephe和具有C-7-catechol相关芳香族化合物的2-isophephes，并进行了抗菌活性评估。事实证明，这些化合物对革兰氏阴性菌，特别是铜绿假单胞菌等耐药病原体具有很强的活性。该系列中活性最高的化合物是（6S，7S）-7- [2-（2-氨基噻唑-4-基）-2-[（Z）-[（1,5-二羟基-4-吡啶idon-2 -（基）甲氧基]亚氨基]乙酰胺基] -3-[[[（（4-甲基-5-羧甲基）噻唑-2-基]硫代]甲基] -8-氧代-1-氮杂-4-硫代双环[4.2.0 ]辛-2-烯-2-羧酸，对临床分离的P，铜绿假单胞菌和鲍曼不动杆菌均表现出强大的体外活性，而鲍曼不动杆菌也对许多抗感染药具有耐药性，

  DOI：

  10.1016/s0968-0896(96)00217-9
• 作为产物：
  描述：

  (6R,7R)-7-Amino-8-oxo-3-(pyridin-4-ylsulfanylmethyl)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 4-methoxy-benzyl ester 在 苯甲醚 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 反应 19.5h， 生成 (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-3-[[(4-pyridyl)thio]methyl]-8-oxo-1-aza-5-thiabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  头孢菌素，2-异烯和2-氧杂异烯与C-3'或C-7邻苯二酚或相关芳香族化合物的合成及构效关系。

  摘要：

  制备了一系列具有C-3'邻苯二酚的（4-吡啶鎓吡啶）甲基的头孢菌素，2-isophephems和2-oxaisocephephe和具有C-7-catechol相关芳香族化合物的2-isophephes，并进行了抗菌活性评估。事实证明，这些化合物对革兰氏阴性菌，特别是铜绿假单胞菌等耐药病原体具有很强的活性。该系列中活性最高的化合物是（6S，7S）-7- [2-（2-氨基噻唑-4-基）-2-[（Z）-[（1,5-二羟基-4-吡啶idon-2 -（基）甲氧基]亚氨基]乙酰胺基] -3-[[[（（4-甲基-5-羧甲基）噻唑-2-基]硫代]甲基] -8-氧代-1-氮杂-4-硫代双环[4.2.0 ]辛-2-烯-2-羧酸，对临床分离的P，铜绿假单胞菌和鲍曼不动杆菌均表现出强大的体外活性，而鲍曼不动杆菌也对许多抗感染药具有耐药性，

  DOI：

  10.1016/s0968-0896(96)00217-9

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.