2-[[2,3-Dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-[3-[[2,3-dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-methylamino]propyl]amino]acetic acid | 439216-87-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[[2,3-Dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-[3-[[2,3-dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-methylamino]propyl]amino]acetic acid
• CAS: 439216-87-2
• 化学式: C₂₈H₂₆Cl₄N₂O₁₆
• 分子量: 788.33
• InChiKey: ASFKDXZYMZZJLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  50
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  220
• 氢给体数：
  1
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2-[[2,3-Dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-[3-[[2,3-dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-methylamino]propyl]amino]acetic acid 在 N-甲基吗啉 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 N-[N',N''-bis-(2,3-dimethoxycarbonyloxy-5,6-dichloro-benzoyl)-N-(methylaminopropyl)glycyl]ampicillin
  参考文献：
  名称：

  Highly Antibacterial Active Aminoacyl Penicillin Conjugates with Acylated Bis-Catecholate Siderophores Based on Secondary Diamino Acids and Related Compounds

  摘要：

  New acylated bis-catecholates and 1,3-benzoxazine-2,4-dione derivatives based on secondary diamino acids (N-(aminoalkyl)glycines, N-aminopropyl-alanine, and N-aminopropyl-4-amino-valeric acid), on N-(aminoalkyl)aminomethyl benzoic acids, on N-(aminoalkyl)aminomethyl phenoxyacetic acids, or on 3,5-diaminobenzoic acid were synthesized as artificial siderophores. The corresponding diamino acids were obtained from the diamines and oxocarboxylic acids by catalytic hydrogenation. The acylated bis-catecholates and 1,3-benzoxazine-2,4-diones were coupled with ampicillin or amoxicillin to new siderophore aminoacylpenicillin conjugates. These conjugates exhibited very strong antibacterial activity in vitro against Gram-negative bacterial pathogens including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens. The ampicillin derivative 7b (HKI 9924154) and the corresponding amoxicillin derivative 8 (HKI 9924155) represent the most active compounds. The conjugates can use bacterial iron siderophore uptake routes to penetrate the Gram-negative outer membrane permeability barrier. This was demonstrated by assays with mutants deficient in components of the iron transport systems. New siderophore penicillin V conjugates with the siderophore component attached to the phenyl ring of penicillin V are inactive against these Gram-negative bacteria.

  DOI：

  10.1021/jm010546b
• 作为产物：
  描述：

  2,3-dichloro-5,6-di-(methoxycarbonyloxy)benzoic acid 在 五氯化磷 、 碳酸氢钠 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 1.0h， 生成 2-[[2,3-Dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-[3-[[2,3-dichloro-5,6-bis(methoxycarbonyloxy)benzoyl]-methylamino]propyl]amino]acetic acid
  参考文献：
  名称：

  Highly Antibacterial Active Aminoacyl Penicillin Conjugates with Acylated Bis-Catecholate Siderophores Based on Secondary Diamino Acids and Related Compounds

  摘要：

  New acylated bis-catecholates and 1,3-benzoxazine-2,4-dione derivatives based on secondary diamino acids (N-(aminoalkyl)glycines, N-aminopropyl-alanine, and N-aminopropyl-4-amino-valeric acid), on N-(aminoalkyl)aminomethyl benzoic acids, on N-(aminoalkyl)aminomethyl phenoxyacetic acids, or on 3,5-diaminobenzoic acid were synthesized as artificial siderophores. The corresponding diamino acids were obtained from the diamines and oxocarboxylic acids by catalytic hydrogenation. The acylated bis-catecholates and 1,3-benzoxazine-2,4-diones were coupled with ampicillin or amoxicillin to new siderophore aminoacylpenicillin conjugates. These conjugates exhibited very strong antibacterial activity in vitro against Gram-negative bacterial pathogens including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens. The ampicillin derivative 7b (HKI 9924154) and the corresponding amoxicillin derivative 8 (HKI 9924155) represent the most active compounds. The conjugates can use bacterial iron siderophore uptake routes to penetrate the Gram-negative outer membrane permeability barrier. This was demonstrated by assays with mutants deficient in components of the iron transport systems. New siderophore penicillin V conjugates with the siderophore component attached to the phenyl ring of penicillin V are inactive against these Gram-negative bacteria.

  DOI：

  10.1021/jm010546b

文献信息

• Catecholate beta-lactam conjugates, method for producing the same and the use thereof
  申请人：Gruenenthal GmbH

  公开号：US20040132707A1

  公开（公告）日：2004-07-08

  Catacholate beta-lactam conjugates, methods for producing these compounds, and compositions containing these compounds useful as siderophores or for treatment of bacterial infections are provided.
• PATHOGEN DETECTION
  申请人：University of Notre Dame Du Lac

  公开号：US20160319322A1

  公开（公告）日：2016-11-03

  A device for detecting bacteria in a sample, comprising: a substrate having a surface; and a plurality of Fe(III)-bound or Fe(III)-binding siderophores specific to the bacteria and covalently attached to the surface; wherein the siderophores are selected from the group consisting of one or more natural siderophores, siderophores having one or more of the formulas described herein, or combination thereof. Methods of detection are also provided.
• REDUCTION-TRIGGERED ANTIBACTERIAL SIDEROMYCINS
  申请人：MILLER Marvin J

  公开号：US20160368878A1

  公开（公告）日：2016-12-22

  A compound is provided, comprising: an Fe(III)-binding or an Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; a drug; and an Fe(III) to Fe(II) reduction triggered linker bound to the drug and the linker or, if no linker is present, then bound to the drug and the siderophore. Compositions and methods including the compound are also provided.
• [DE] SUBSTITUIERTE CATECHOLDERIVATE ABGELEITET VON MEHRBASISCHEN SEKUNDÄREN AMINOSÄUREN, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE ANWENDUNG<br/>[EN] SUBSTITUTED CATECHOL DERIVATIVES DERIVED FROM POLYBASIC SECONDARY AMINO ACIDS, METHOD FOR PRODUCTION AND USE THEREOF<br/>[FR] DERIVES DE CATECHOL SUBSTITUES, DERIVANT D'ACIDES AMINES SECONDAIRES POLYBASIQUES, LEUR PROCEDE DE PRODUCTION ET LEUR UTILISATION
  申请人：GRUENENTHAL GMBH

  公开号：WO2002085841A2

  公开（公告）日：2002-10-31

  Die Erfindung betrifft neue substituierte Catecholderivate abgeleitet von mehrbasischen sekundären Aminosäuren und analogen Strukturen der allgemeinen Formel (I). Die erfindungsgemässen Verbindungen sind bei Mykobakterien sowie Gram-negativen Bakterienstämmen, insbesondere Pseudomonaden, E.coli-und Salmonella-Stämmen, als Siderophore wirksam. Sie können als Transportvehikel zur Einschleusung von Wirkstoffen, z.B Antibiotika (als 'Siderophor-Antibiotikakonjugate'), in Bakterienzellen dienen und damit deren antibakterielle Wirksamkeit in stärkerem Masse verbessern bzw. erweitern als bisher bekannte Verbindungen. Ausserdem sind die genannten Verbindungen als potentielle Prodrugformen für Eisenchelatoren geeignet zur Verwendung bei Erkrankungen, die auf einer Störung des Eisenstoffwechsels beruhen. Formel (I), wobei R1 = H, Alkyl, Aryl, R?2 und R3¿ H oder Acyl, R?4 und R5¿ = H, Alkyl, Aryl und R?6 bzw. R7¿ = H, Alkyl Oder Catecholatgruppen, gegebenenfalls in acylierter Form oder zusammen mit Spacergruppen, X und Z direkte oder durch bestimmte Spacergruppen unterbrochene Bindungen und Y = OH (als freie Säuren, in Form ihrer Salze oder ihrer leicht spaltbaren Ester) bedeuten.
• Highly Antibacterial Active Aminoacyl Penicillin Conjugates with Acylated Bis-Catecholate Siderophores Based on Secondary Diamino Acids and Related Compounds
  作者：Lothar Heinisch、Steffen Wittmann、Thomas Stoiber、Albrecht Berg、Dorothe Ankel-Fuchs、Ute Möllmann

  DOI：10.1021/jm010546b

  日期：2002.7.1

  New acylated bis-catecholates and 1,3-benzoxazine-2,4-dione derivatives based on secondary diamino acids (N-(aminoalkyl)glycines, N-aminopropyl-alanine, and N-aminopropyl-4-amino-valeric acid), on N-(aminoalkyl)aminomethyl benzoic acids, on N-(aminoalkyl)aminomethyl phenoxyacetic acids, or on 3,5-diaminobenzoic acid were synthesized as artificial siderophores. The corresponding diamino acids were obtained from the diamines and oxocarboxylic acids by catalytic hydrogenation. The acylated bis-catecholates and 1,3-benzoxazine-2,4-diones were coupled with ampicillin or amoxicillin to new siderophore aminoacylpenicillin conjugates. These conjugates exhibited very strong antibacterial activity in vitro against Gram-negative bacterial pathogens including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens. The ampicillin derivative 7b (HKI 9924154) and the corresponding amoxicillin derivative 8 (HKI 9924155) represent the most active compounds. The conjugates can use bacterial iron siderophore uptake routes to penetrate the Gram-negative outer membrane permeability barrier. This was demonstrated by assays with mutants deficient in components of the iron transport systems. New siderophore penicillin V conjugates with the siderophore component attached to the phenyl ring of penicillin V are inactive against these Gram-negative bacteria.