3,5-bis-[(8-methoxycarbonyloxy-2,4-dioxo-1,3-benzoxazin-3-yl)-acetylamino]-benzoic acid | 212777-05-4

• 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: 3,5-bis-[(8-methoxycarbonyloxy-2,4-dioxo-1,3-benzoxazin-3-yl)-acetylamino]-benzoic acid
• 英文别名: 3,5-Bis[[2-(8-methoxycarbonyloxy-2,4-dioxo-1,3-benzoxazin-3-yl)acetyl]amino]benzoic acid
• CAS: 212777-05-4
• 化学式: C₃₁H₂₂N₄O₁₆
• 分子量: 706.533
• InChiKey: NFHNXMDJXAKTGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  51
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  260
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  3,5-bis-[(8-methoxycarbonyloxy-2,4-dioxo-1,3-benzoxazin-3-yl)-acetylamino]-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-{[3,5-N',N''-bis-(8-methoxycarbonyloxy-1,3-benzoxazine-2,4-dione-3-yl)acetylamino]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：

  3,5-二氨基苯甲酸 、 (8-methoxycarbonyloxy-1,3-benzoxazine-2,4-dione-3-yl)acetyl chloride 以 碳酸氢钠 为溶剂， 以53%的产率得到3,5-bis-[(8-methoxycarbonyloxy-2,4-dioxo-1,3-benzoxazin-3-yl)-acetylamino]-benzoic acid
  参考文献：
  名称：

  Benzoxazinedione derivatives, method of producing them and uses thereof

  摘要：

  该发明涉及与以下式I对应的新苯并噁唑二酮衍生物：##STR1## 其中R.sup.1=H或羧基烷基，R.sup.2=H、烷基或苯基，而R.sup.3代表源自氨基酸、二肽和醛腙或其与活性成分（如抗生素）的结合物的不同酸基。这些化合物可以以游离酸的形式存在，也可以以其盐的形式或易于水解的酯的形式存在。根据本发明的化合物构成了杂环保护的邻苯二酚衍生物，对革兰氏阴性细菌株，特别是对铜绿假单胞菌和大肠杆菌和沙门氏菌株具有有效作用。作为与活性成分（例如抗生素）结合物的形式（如“铁载体-抗生素结合物”），它们可以将后者运送到细菌细胞内，并可以改善或延长其抗菌作用，有时甚至相对于对其他β-内酰胺类抗生素具有耐药性的细菌株。此外，所述化合物作为铁螯合剂的潜在前药形式，适用于用于对抗由铁代谢紊乱引起的疾病。该发明可应用于制药研究、制药工业和农业中。

  公开号：

  US06013647A1

文献信息

• Benzoxazinedione derivatives, method of producing them and uses thereof
  申请人：Gruenenthal GmbH

  公开号：US06013647A1

  公开（公告）日：2000-01-11

  This invention relates to new benzoxazinedione derivatives corresponding to the formula I: ##STR1## wherein R.sup.1 =H or carboxyalkyl, R.sup.2 =H, alkyl or phenyl, and R.sup.3 represents different acid groups derived from amino acids, dipeptides and hydrazones or conjugates thereof with active ingredients, e.g. antibiotics. The compounds may be present as free acids, in the form of their salts or as readily cleavable esters. The compounds according to the invention constitute heterocyclically protected catechol derivatives and are effective as siderophores against gram-negative bacterial strains, particularly against Pseudomonads and strains of E. coli and Salmonella. In the form of their conjugates with active ingredients, e.g. antibiotics (as "siderophore-antibiotic conjugates"), they can transport the latter into bacterial cells and can improve or extend the antibacterial effect thereof, sometimes even in relation to bacterial strains which are resistant to other .beta.-lactams. In addition, said compounds, as potential prodrug forms for iron chelating agents, are suitable for use against diseases which are caused by a disorder of the iron metabolism. The invention can be employed in pharmaceutical research and in the pharmaceutical industry, and in agriculture.

  该发明涉及与以下式I对应的新苯并噁唑二酮衍生物：##STR1## 其中R.sup.1=H或羧基烷基，R.sup.2=H、烷基或苯基，而R.sup.3代表源自氨基酸、二肽和醛腙或其与活性成分（如抗生素）的结合物的不同酸基。这些化合物可以以游离酸的形式存在，也可以以其盐的形式或易于水解的酯的形式存在。根据本发明的化合物构成了杂环保护的邻苯二酚衍生物，对革兰氏阴性细菌株，特别是对铜绿假单胞菌和大肠杆菌和沙门氏菌株具有有效作用。作为与活性成分（例如抗生素）结合物的形式（如“铁载体-抗生素结合物”），它们可以将后者运送到细菌细胞内，并可以改善或延长其抗菌作用，有时甚至相对于对其他β-内酰胺类抗生素具有耐药性的细菌株。此外，所述化合物作为铁螯合剂的潜在前药形式，适用于用于对抗由铁代谢紊乱引起的疾病。该发明可应用于制药研究、制药工业和农业中。
• 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.
• 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.