7beta-[(Z)-2-(2-氨基噻唑-4-基)-2-(1-羧基-1-甲基乙氧基亚氨基)乙酰氨基]-3-乙酰氧基甲基-3-头孢烯-4-羧酸 | 73443-60-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: 7beta-[(Z)-2-(2-氨基噻唑-4-基)-2-(1-羧基-1-甲基乙氧基亚氨基)乙酰氨基]-3-乙酰氧基甲基-3-头孢烯-4-羧酸
• 英文名称: acide (acetoxy methyl)-3(<<(carboxy-1 methyl-1 ethoxy)-imino-2 Z (amino-2 thiazolyl-4)-2>-acetyl>-amino)-7 β cepheme-3 carboxylique-4
• 英文别名: (6R,7R)-3-Acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]ceph-3-em-4-carboxylic acid；(6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-acetoxymethyl-ceph-3-em-4carboxylic acid；acide (acetoxy methyl)-3({[(carboxy-1 methyl-1 ethoxy)-imino-2 Z (amino-2 thiazolyl-4)-2]-acetyl}-amino)-7 β cepheme-3 carboxylique-4；(6R,7R)-3-(acetyloxymethyl)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 73443-60-4
• 化学式: C₁₉H₂₁N₅O₉S₂
• 分子量: 527.536
• InChiKey: YWJLSGRPSYHXGF-LGAWNBMASA-N

物化性质

• 密度：
  1.75±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  264
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  7beta-[(Z)-2-(2-氨基噻唑-4-基)-2-(1-羧基-1-甲基乙氧基亚氨基)乙酰氨基]-3-乙酰氧基甲基-3-头孢烯-4-羧酸 生成 (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-3-[(4-methylsulfanylpyridin-1-ium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  KAMACHI, HAJIME;OKUMURA, JUN;NAITO, TAKAYUKI;OKA, MASAHISA

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基-2-丙基2-{[(Z)-{2-乙氧基-2-氧代-1-[2-(三苯甲基氨基)-1,3-噻唑-4-基]亚乙基}氨基]氧基}-2-甲基丙酸酯 在 氢氧化钾 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.25h， 生成 7beta-[(Z)-2-(2-氨基噻唑-4-基)-2-(1-羧基-1-甲基乙氧基亚氨基)乙酰氨基]-3-乙酰氧基甲基-3-头孢烯-4-羧酸
  参考文献：
  名称：

  Bucourt; Heymes; Perronnet, European Journal of Medicinal Chemistry, 1981, vol. 16, # 4, p. 307 - 316

  摘要：

  DOI：

文献信息

• Cephalosporin antibiotics
  申请人：Glaxo Group Limited

  公开号：US04427675A1

  公开（公告）日：1984-01-24

  Cephalosporin antibiotics of general formula ##STR1## (wherein R.sup.a and R.sup.b, which may be the same or different, each represent a C.sub.1-4 alkyl group, or together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene group). These compounds exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms. Particularly effective compounds of formula (I) are (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetami o]-3-(pyridazinium-1-ylmethyl)ceph-3-em-4-carboxylate and (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(t-carboxycyclobut-1-oxyimino)ace tamido]-3-(pyridazinium-1-ylmethyl)ceph-3-em-4-carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I), compositions containing the antibiotic compounds of the invention and a method of combatting bacterial infection utilizing the antibiotics.

  头孢菌素抗生素的一般结构式为##STR1##（其中R.sup.a和R.sup.b，可能相同也可能不同，每个代表一个C.sub.1-4烷基基团，或者与它们连接的碳原子一起形成一个C.sub.3-7环烷基亚基团）。这些化合物表现出广谱抗生素活性，对革兰氏阴性生物如假单胞菌菌株的活性异常高。特别有效的化合物的结构式（I）为（6R,7R）-7-[(Z)-2-(2-氨基噻唑-4-基)-2-(2-羧基丙-2-氧基亚氨基)乙酰胺]-3-(吡啶嘧啶-1-基甲基)头孢-3-烯-4-羧酸酯和（6R,7R）-7-[(Z)-2-(2-氨基噻唑-4-基)-2-(t-羧基环丁-1-氧基亚氨基)乙酰胺]-3-(吡啶嘧啶-1-基甲基)头孢-3-烯-4-羧酸酯。本发明还包括化合物（I）的无毒盐和无毒代谢易降解酯，含有本发明抗生素化合物的组合物以及利用这些抗生素对抗细菌感染的方法。
• 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.
• OCALLAGHAN, C. H.;LIVERMORE, D. G. H.;NEWALL, C. E.
  作者：OCALLAGHAN, C. H.、LIVERMORE, D. G. H.、NEWALL, C. E.

  DOI：——

  日期：——
• OCALLAGHAN, C. H.;AYRES, B. E.;LIVERMORE, D. G. H.;NEWALL, C. E.;WEIR, N.+
  作者：OCALLAGHAN, C. H.、AYRES, B. E.、LIVERMORE, D. G. H.、NEWALL, C. E.、WEIR, N.+

  DOI：——

  日期：——
• NOVEL 3-FUSED PYRIDINIUMMETHYL CEPHALOSPORINS
  申请人：CHEIL FOODS & CHEMICALS, INC.

  公开号：EP0589914A1

  公开（公告）日：1994-04-06