7-(4-(6-((tert-butoxycarbonyl)amino)hexanoyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1407510-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-(4-(6-((tert-butoxycarbonyl)amino)hexanoyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-Cyclopropyl-6-fluoro-7-[4-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid；1-cyclopropyl-6-fluoro-7-[4-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 1407510-82-0
• 化学式: C₂₈H₃₇FN₄O₆
• 分子量: 544.623
• InChiKey: NWDGSMNWLKKDSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  7-(4-(6-((tert-butoxycarbonyl)amino)hexanoyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 3.0h， 以98%的产率得到7-(4-(6-aminohexanoyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid trifluoroacetate
  参考文献：
  名称：

  Siderophore-Mediated Cargo Delivery to the Cytoplasm of Escherichia coli and Pseudomonas aeruginosa: Syntheses of Monofunctionalized Enterobactin Scaffolds and Evaluation of Enterobactin–Cargo Conjugate Uptake

  摘要：

  The design and syntheses of monofunctionalized enterobactin (Ent, L- and D-isomers) scaffolds where one catecholate moiety of enterobactin houses an alkene, aldehyde, or carboxylic acid at the C5 position are described. These molecules are key precursors to a family of 10 enterobactin-cargo conjugates presented in this work, which were designed to probe the extent to which the Gram-negative ferric enterobactin uptake and processing machinery recognizes, transports, and utilizes derivatized enterobactin scaffolds. A series of growth recovery assays employing enterobactin-deficient E. coli ATCC 33475 (ent-) revealed that six conjugates based on L-Ent having relatively small cargos promoted E. coli growth under iron limiting conditions whereas negligible-to-no growth recovery was observed for four conjugates with relatively large cargos. No growth recovery was observed for the enterobactin receptor deficient strain of E. coli H1187 (fepA-) or the enterobactin esterase deficient derivative of E. coli K-12 JW0576 (fes-), or when the D-isomer of enterobactin was employed These results demonstrate that the E. coli ferric enterobactin transport machinery identifies and delivers select cargo-modified scaffolds to the E. coli cytoplasm. Pseudomonas aeruginosa PAO1 K648 (pvd-, pch-) exhibited greater promiscuity than that of E. coli for the uptake and utilization of the enterobactin-cargo conjugates, and growth promotion was observed for eight conjugates under iron-limiting conditions. Enterobactin may be utilized for delivering molecular cargos via its transport machinery to the cytoplasm of E. coli and P. aeruginosa thereby providing a means to overcome the Gram-negative outer membrane permeability barrier.

  DOI：

  10.1021/ja3077268
• 作为产物：
  描述：

  叔丁氧羰酰基6-氨基己酸 、 环丙沙星 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成 7-(4-(6-((tert-butoxycarbonyl)amino)hexanoyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  ENTEROBACTIN CONJUGATES AND USES THEREOF

  摘要：

  本发明提供了新型肠杆菌铁胞内载体共轭物，如式(I)化合物及其盐，其中X是载体，可以是抗生素、荧光素或生物素。本发明还提供了涉及式(I)化合物的络合物、组合物、试剂盒和方法，用于将载体传递给细菌，治疗受试者的细菌感染、囊性纤维化和/或炎症性肠病，预防受试者的细菌感染、囊性纤维化和/或炎症性肠病，抑制或杀死细菌的生长，或确定生物样品中细菌的浓度。在某些实施例中，细菌是革兰氏阴性细菌。

  公开号：

  US20150105337A1

文献信息

• Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space
  作者：Audrey G. Ross、Bret M. Benton、Donovan Chin、Gianfranco De Pascale、John Fuller、Jennifer A. Leeds、Folkert Reck、Daryl L. Richie、Jason Vo、Matthew J. LaMarche

  DOI：10.1016/j.bmcl.2015.07.010

  日期：2015.9

  We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics. (C) 2015 Elsevier Ltd. All rights reserved.
• Siderophore-Mediated Cargo Delivery to the Cytoplasm of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>: Syntheses of Monofunctionalized Enterobactin Scaffolds and Evaluation of Enterobactin–Cargo Conjugate Uptake
  作者：Tengfei Zheng、Justin L. Bullock、Elizabeth M. Nolan

  DOI：10.1021/ja3077268

  日期：2012.11.7

  The design and syntheses of monofunctionalized enterobactin (Ent, L- and D-isomers) scaffolds where one catecholate moiety of enterobactin houses an alkene, aldehyde, or carboxylic acid at the C5 position are described. These molecules are key precursors to a family of 10 enterobactin-cargo conjugates presented in this work, which were designed to probe the extent to which the Gram-negative ferric enterobactin uptake and processing machinery recognizes, transports, and utilizes derivatized enterobactin scaffolds. A series of growth recovery assays employing enterobactin-deficient E. coli ATCC 33475 (ent-) revealed that six conjugates based on L-Ent having relatively small cargos promoted E. coli growth under iron limiting conditions whereas negligible-to-no growth recovery was observed for four conjugates with relatively large cargos. No growth recovery was observed for the enterobactin receptor deficient strain of E. coli H1187 (fepA-) or the enterobactin esterase deficient derivative of E. coli K-12 JW0576 (fes-), or when the D-isomer of enterobactin was employed These results demonstrate that the E. coli ferric enterobactin transport machinery identifies and delivers select cargo-modified scaffolds to the E. coli cytoplasm. Pseudomonas aeruginosa PAO1 K648 (pvd-, pch-) exhibited greater promiscuity than that of E. coli for the uptake and utilization of the enterobactin-cargo conjugates, and growth promotion was observed for eight conjugates under iron-limiting conditions. Enterobactin may be utilized for delivering molecular cargos via its transport machinery to the cytoplasm of E. coli and P. aeruginosa thereby providing a means to overcome the Gram-negative outer membrane permeability barrier.
• ENTEROBACTIN CONJUGATES AND USES THEREOF
  申请人：MASSACHUSETTS INSTITUTE OF TECHNOLOGY

  公开号：US20150105337A1

  公开（公告）日：2015-04-16

  The present invention provides novel enterobactin-cargo conjugates, such as compounds of Formula (I), and salts thereof, where X is the cargo and may be an antibiotic, a fluorophore, or biotin. The present invention also provides complexes, compositions, kits, and methods that involve the compounds of Formula (I) and are useful in delivering a cargo to a bacterium, treating a bacterial infection, cystic fibrosis, and/or inflammatory bowel disease in a subject, preventing a bacterial infection, cystic fibrosis, and/or inflammatory bowel disease in a subject, inhibiting the growth of or killing a bacterium, or determining the concentration of a bacterium in a biological sample. In certain embodiments, the bacterium is a Gram-negative bacterium.

  本发明提供了新型肠杆菌铁胞内载体共轭物，如式(I)化合物及其盐，其中X是载体，可以是抗生素、荧光素或生物素。本发明还提供了涉及式(I)化合物的络合物、组合物、试剂盒和方法，用于将载体传递给细菌，治疗受试者的细菌感染、囊性纤维化和/或炎症性肠病，预防受试者的细菌感染、囊性纤维化和/或炎症性肠病，抑制或杀死细菌的生长，或确定生物样品中细菌的浓度。在某些实施例中，细菌是革兰氏阴性细菌。