3,5-bis-(2,3-Diacetoxybenzoylamino)-benzoic Acid | 201296-72-2

• 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: 3,5-bis-(2,3-Diacetoxybenzoylamino)-benzoic Acid
• 英文别名: 3,5-Bis[(2,3-diacetyloxybenzoyl)amino]benzoic acid
• CAS: 201296-72-2
• 化学式: C₂₉H₂₄N₂O₁₂
• 分子量: 592.516
• InChiKey: PQSIBPCUZIOUPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  201
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  氯甲酸甲酯 、 3,5-bis-(2,3-Diacetoxybenzoylamino)-benzoic Acid 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成
  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：

  3,5-二氨基苯甲酸 、 2,3-diacetoxybenzoyl chloride 在 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以55%的产率得到3,5-bis-(2,3-Diacetoxybenzoylamino)-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] NEUE SYNTHETISCHE CATECHOLDERIVATE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG<br/>[EN] NEW SYNTHETIC CATECHOL DERIVATIVES, METHOD FOR PRODUCTION AND USE THEREOF<br/>[FR] NOUVEAUX DERIVES SYNTHETIQUES DE CATECHOL, LEUR PROCEDE DE PRODUCTION ET LEUR UTILISATION
  申请人：GRÜNENTHAL GMBH

  公开号：WO1997049670A1

  公开（公告）日：1997-12-31

  (DE) Die Erfindung betrifft neue Catecholderivate der allgemeinen Formel (I), bei denen Azomethincarbonsäurereste, Azobenzolcarbonsäurereste, Benzhydrazonreste, Aminobenzoesäurereste, Aminosäurereste oder Dipeptide, Pyrrolidin- und/oder Oxazolidincarbonsäurereste sowie Formylcarboxymethyloximreste als Strukturelemente fungieren, und deren Konjugate mit Wirkstoffen, insbesondere Antibiotika. Die erfindungsgemäßen Verbindungen sind bei gramnegativen Bakterienstämmen, insbesondere $i(Pseudomonaden), $i(E. coli-, Salmonella-, Klebsiella- und Proteus)-Stämmen als Siderophore wirksam und können in Form ihrer Konjugate mit Wirkstoffen, z.B. Antibiotika (als 'Siderophor-Antibiotikakonjugate') diese in Bakterienzellen einschleusen und deren antibakterielle Wirksamkeit verbessern bzw. erweitern, zum Teil auch bei gegenüber anderen $g(b)-Lactamen resistenten Bakterienstämmen. Außerdem sind die genannten Verbindungen als Eisenchelatoren zur Verwendung bei Erkrankungen geeignet, die auf einer Störung des Eisenstoffwechsels beruhen. In der obengenannten Formel (I) bedeuten R1 = OH oder OAcyl und R2 in 3- und/oder 4-Position aromatische Azomethincarbonsäurereste bzw. Azobenzolcarbonsäurereste, Benzhydrazonreste, Aminobenzoesäurereste, Aminosäurereste, Pyrrolidin- und/oder Oxazolidincarbonsäurereste und Formylcarboxymethyloxime und/oder Konjugate mit Wirkstoffen, insbesondere Antibiotika. Die genannten Verbindungen können als freie Säuren in Form ihrer Salze oder als leicht spaltbare Ester vorliegen.(EN) The invention concerns new catechol derivatives of the general formula (I), in which azomethine-carboxylic acid rests, azobenzene-carboxylic acid rests, benzhydrazon rests, aminobenzoic acid rests and amino acid rests or dipeptides, pyrrolidine and/or oxazolidine carboxylic acid rests and formylcarboxymethyloxime rests act as structural elements, and the conjugates thereof with active ingredients such as antibiotics. The compounds according to the invention act as siderophors in gram-negative bacterial strains, in particular in $i(pseudomonas) and strains of $i(E. coli, salmonella, klebsiella and proteus), and can in the form of their conjugates with active ingredients, e.g. antibiotics (as 'siderophor-antibiotic conjugates'), inject the latter into bacterial cells to improve or extend the anti-bacterial effectiveness of the cells, partly also for bacterial strains that are resistant to other $g(b)-lactams. In addition the said compounds are suitable for using as iron chelating agents for illnesses related to disruption of the iron metabolism. In the general formula (I), R1 = OH or OAcyl and R2 in third and/or fourth position means aromatic azomethine-carboxylic acid rests or azobenzene-carboxylic acid rests, benzhydrazon rests, aminobenzoic acid rests and amino acid rests, pyrrolidin and/or oxazolidine carboxylic acid rests and formylcarboxymethyloxime and/or conjugates with active ingredients, in particular antibiotics. Said compounds can be free acids in the form of their salts or esters that can be cleaved easily.(FR) L'invention concerne de nouveaux dérivés de catéchol de la formule générale (I), dans lesquels des restes acide carboxylique d'azométhine, des restes acide carboxylique d'azobenzène, des restes benzhydrazone, des restes acide aminobenzoïque, des restes aminoacides ou bien des dipeptides, des restes acide carboxylique de pyrrolidine et/ou d'oxazolidine ainsi que des restes formylcarboxyméthyloxime font office d'éléments structuraux, et leurs conjugués avec des principes actifs, notamment des antibiotiques. Ces composés agissent comme sidérophores dans des souches bactériennes Gram négatif, notamment des $i(pseudomonas), et des souches de $i(E. coli, salmonella, klebsiella, et proteus), et peuvent, sous forme de leurs conjugués avec des principes actifs, par exemple des antibiotiques (en tant que 'conjugués sidérophores-antibiotiques'), injecter ceux-ci dans des cellules bactériennes et améliorer ou élargir leur efficacité antibactérienne, en partie également en présence de souches bactériennes résistantes à d'autres $g(b)-lactames. En outre, les composés précités s'utilisent comme chélateurs du fer pour des maladies liées à un dérèglement du métabolisme ferrique. Dans la formule générale (I), R1 = OH ou bien OAcyl et R2 en position 3 ou 4 désigne des restes aromatiques acide carboxylique d'azométhine ou bien des restes acide carboxylique d'azobenzène, des restes benzhydrazone, des restes acide aminobenzoïque, des restes aminoacides, des restes acide carboxylique de pyrrolidine et/ou d'oxazolidine et du formylcarboxyméthyloxime et/ou des conjugués avec des principes actifs, notamment des antibiotiques. Lesdits composés peuvent se présenter comme des acides libres sous la forme de leurs sels ou bien comme des esters facilement clivables.

  该发明涉及一类新型类别化合物，通常称为（I）式的新酚类衍生物，其中包含多种结构元素，如亚胺甲基二羧酸酯、亚苯基二羧酸酯、呋喃二键、氨基苯二羧酸酯、氨基酸酯、二肽、吡咯二胺和/或环噻吩二胺二羧酸酯、以及甲酰羟基或羟哇基二羧酸酯、羟哇基二羧酸酯，以及与活性成分（尤其是抗生素）的共轭物。该发明所涉及的化合物能够在革兰氏阴性菌属（如大肠杆菌、沙父菌、金黄色葡萄球菌和铜绿假单胞菌）以及其它革兰氏阴性菌属中作为配位因子（如细菌的 siderophore）表现出活性，并且可以作为配位化合物与抗菌素之间的共轭物，从而将抗菌素注入细菌细胞内，以提高或增强细菌细胞的抗菌效果，部分菌也可能表现出抗菌效果的扩大。此外，这些化合物还可以作为配位成分应用于因为铁的转运障碍而导致的疾病。在（I）式中，R1=羟基或甲氧基，且R2在3位或/和4位均为芳香二羧酸酯，不仅包括亚胺甲基二羧酸酯、亚苯基二羧酸酯、呋喃二键、氨基苯二羧酸酯、氨基酸酯，以及吡咯二胺和/或环噻吩二胺二羧酸酯，还包含甲酰羟基或羟哇基二羧酸酯以及与其共轭的活性成分（尤其是抗生素）。这些化合物还可以以自由酸的形式出现，即它们的盐或易于水解的酯。
• NEUE SYNTHETISCHE CATECHOLDERIVATE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG
  申请人：Grünenthal GmbH

  公开号：EP0907633A1

  公开（公告）日：1999-04-14
• 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.
• US6380181B1
  申请人：——

  公开号：US6380181B1

  公开（公告）日：2002-04-30