2-[[(2,3-Diacetyloxybenzoyl)-[3-[(2,3-diacetyloxybenzoyl)-methylamino]propyl]amino]methyl]benzoic acid | 439216-89-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[[(2,3-Diacetyloxybenzoyl)-[3-[(2,3-diacetyloxybenzoyl)-methylamino]propyl]amino]methyl]benzoic acid
• CAS: 439216-89-4
• 化学式: C₃₄H₃₄N₂O₁₂
• 分子量: 662.65
• InChiKey: DCELNRNPESSFOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  183
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-[[(2,3-Diacetyloxybenzoyl)-[3-[(2,3-diacetyloxybenzoyl)-methylamino]propyl]amino]methyl]benzoic 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-{2-[N,N'-bis-(2,3-diacetoxybenzoyl)-N-(methylaminopropyl)aminomethyl]benzoyl}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：

  邻羧基苯甲醛 在 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 生成 2-[[(2,3-Diacetyloxybenzoyl)-[3-[(2,3-diacetyloxybenzoyl)-methylamino]propyl]amino]methyl]benzoic 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

• [DE] CATECHOLAT-CATECHOLATE BETA-LACTAM CONJUGATES, METHOD FOR PRODUCING THE SAME AND THE USE THEREOFCONJUGUES CATECHOL-BETA-LACTAME, PROCEDES DE PRODUCTION ET UTILISATIONS ASSOCIES20020912<br/>[EN] CATECHOLATE BETA-LACTAM CONJUGATES, METHOD FOR PRODUCING THE SAME AND THE USE THEREOF<br/>[FR] CONJUGUES CATECHOL-BETA-LACTAME, PROCEDES DE PRODUCTION ET UTILISATIONS ASSOCIES
  申请人：GRUENENTHAL GMBH

  公开号：WO2002070016A2

  公开（公告）日：2002-09-12

  Die Erfindung betrifft neue substituierte Catecholderivateabgeleitet von mehrbasisschen sekundären Aminosäuren und analogen Strukturen der allgemeinen Formel (I). Die Erfindungsgemä = H, Alkyl, Aryl, R<2> und R<3> H oder Acyl, R<4> und R<5> = H, Alkyl, Aryl und R<6> bzw. R<7> = 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.

  本发明涉及新的取代的儿茶酚衍生物，其衍生自多碱性次级氨基酸和类似的结构，其通用式为(I)。该发明的化合物在分枝杆菌和革兰氏阴性细菌株，特别是假单胞菌、大肠杆菌和沙门氏菌株中作为铁载体有效。它们可以作为运输工具，将药物如抗生素（作为“铁载体抗生素结合物”）引入细菌细胞中，从而比以前已知的化合物更有效地提高或扩展其抗菌活性。此外，所述化合物还可作为铁螯合剂的潜在前体形式，适用于基于铁代谢障碍的疾病的治疗。其中，式(I)中R?1> = H、烷基、芳基，R<2>和R<3>为H或酰基，R<4>和R<5>为H、烷基、芳基，R<6>和R<7>为H、烷基或儿茶酚基，可能为酰基化形式或与间隔基团一起，X和Z为直接或通过特定的间隔基团断裂的键，Y为OH（作为游离酸、其盐或易于水解的酯的形式）。
• CATECHOLAT-BETA-LAKTAMKONJUGATE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE ANWENDUNG
  申请人：Grünenthal GmbH

  公开号：EP1370296A2

  公开（公告）日：2003-12-17
• 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.