1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[1'-(4'-N-(succinyloxymethyleneoxycarbonyl)piperazinyl)]-3-quinolinecarboxylic acid | 353289-19-7

• 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: 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[1'-(4'-N-(succinyloxymethyleneoxycarbonyl)piperazinyl)]-3-quinolinecarboxylic acid
• 英文别名: 7-[4-(3-Carboxypropanoyloxymethoxycarbonyl)piperazin-1-yl]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 353289-19-7
• 化学式: C₂₂H₂₄FN₃O₉
• 分子量: 493.446
• InChiKey: BSFHCAFTLDISRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[1'-(4'-N-(succinyloxymethyleneoxycarbonyl)piperazinyl)]-3-quinolinecarboxylic acid 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 14.0h， 生成 (4R)-3-[3-[[4-[[4-(3-carboxy-1-ethyl-6-fluoro-4-oxoquinolin-7-yl)piperazine-1-carbonyl]oxymethoxy]-4-oxobutanoyl]amino]propyl]-2-[(4R)-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-thiazol-4-yl]-1,3-thiazolidine-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin

  摘要：

  吡咯菌素是一种常见于铜绿假单胞菌和其他几种致病菌的铁载体。先前合成了一种在N3″位点功能化的吡咯菌素，其末端连接了一个丙胺基团。在本研究中，我们证实这种类似物能够与吡咯菌素的外膜受体FptA结合，并高效地将铁(III)转运至细菌内部。这种功能化的吡咯菌素似乎是抗生素载体化的良好候选药物，适用于特洛伊木马前药策略。在此背景下，通过稳定的或可在体内水解的接头臂，将吡咯菌素与三种氟喹诺酮类抗生素（诺氟沙星、环丙沙星和N-脱甲基氧氟沙星）合成了共轭物。某些吡咯菌素-氟喹诺酮共轭物在一些铜绿假单胞菌菌株的生长抑制实验中展现出了抗菌活性。然而，这些活性弱于单一抗生素。这些特性似乎与共轭物的溶解性和生物利用度以及所用接头臂的稳定性有关。

  DOI：

  10.1039/c1ob06250f
• 作为产物：
  描述：

  诺氟沙星 在 silver carbonate 、 1,8-双二甲氨基萘 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[1'-(4'-N-(succinyloxymethyleneoxycarbonyl)piperazinyl)]-3-quinolinecarboxylic acid
  参考文献：
  名称：

  Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin

  摘要：

  吡咯菌素是一种常见于铜绿假单胞菌和其他几种致病菌的铁载体。先前合成了一种在N3″位点功能化的吡咯菌素，其末端连接了一个丙胺基团。在本研究中，我们证实这种类似物能够与吡咯菌素的外膜受体FptA结合，并高效地将铁(III)转运至细菌内部。这种功能化的吡咯菌素似乎是抗生素载体化的良好候选药物，适用于特洛伊木马前药策略。在此背景下，通过稳定的或可在体内水解的接头臂，将吡咯菌素与三种氟喹诺酮类抗生素（诺氟沙星、环丙沙星和N-脱甲基氧氟沙星）合成了共轭物。某些吡咯菌素-氟喹诺酮共轭物在一些铜绿假单胞菌菌株的生长抑制实验中展现出了抗菌活性。然而，这些活性弱于单一抗生素。这些特性似乎与共轭物的溶解性和生物利用度以及所用接头臂的稳定性有关。

  DOI：

  10.1039/c1ob06250f

文献信息

• Synthesis of pyochelin–norfloxacin conjugates
  作者：Freddy Rivault、Clémence Liébert、Alain Burger、Françoise Hoegy、Mohamed A. Abdallah、Isabelle J. Schalk、Gaëtan L.A. Mislin

  DOI：10.1016/j.bmcl.2006.11.005

  日期：2007.2

  Using synthetic functionalized analogues of pyochelin, a siderophore common to several pathogenic Pseudomonas and Burkholderia species, four fluoroquinolone-pyochelin conjugates were efficiently synthesized and evaluated for their biological activities. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and Activities of Pyoverdin−Quinolone Adducts: A Prospective Approach to a Specific Therapy Against <i>Pseudomonas a</i><i>eruginosa</i>
  作者：Christophe Hennard、Que Chi Truong、Jean-François Desnottes、Jean-Marc Paris、Nicole J. Moreau、Mohamed A. Abdallah

  DOI：10.1021/jm990508g

  日期：2001.6.1

  Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia: coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of Fe-55 using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with II? aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is liabile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.
• Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin
  作者：Sabrina Noël、Véronique Gasser、Bénédicte Pesset、Françoise Hoegy、Didier Rognan、Isabelle J. Schalk、Gaëtan L. A. Mislin

  DOI：10.1039/c1ob06250f

  日期：——

  Pyochelin is a siderophore common to Pseudomonas aeruginosa and several other pathogenic bacteria. A pyochelin functionalized at the N3′′ position with a propyl-amine extension was previously synthesized. In the present work we proved that this analog binds FptA, the pyochelin outer membrane receptor, and transports iron(III) efficiently into bacteria. This functionalized pyochelin seemed to be a good candidate for antibiotic vectorization in the framework of a Trojan horse prodrug strategy. In this context, conjugates between pyochelin and three fluoroquinolones (norfloxacin, ciprofloxacin and N-desmethyl-ofloxacin) were synthesized with a spacer arm that was either stable or hydrolyzable in vivo. Some pyochelin–fluoroquinolone conjugates had antibacterial activities in growth inhibition experiments on several P. aeruginosa strains. However, these activities were weaker than those of the antibiotic alone. These properties appeared to be related to both the solubility and bioavailability of conjugates and to the stability of the spacer arm used.

  吡咯菌素是一种常见于铜绿假单胞菌和其他几种致病菌的铁载体。先前合成了一种在N3″位点功能化的吡咯菌素，其末端连接了一个丙胺基团。在本研究中，我们证实这种类似物能够与吡咯菌素的外膜受体FptA结合，并高效地将铁(III)转运至细菌内部。这种功能化的吡咯菌素似乎是抗生素载体化的良好候选药物，适用于特洛伊木马前药策略。在此背景下，通过稳定的或可在体内水解的接头臂，将吡咯菌素与三种氟喹诺酮类抗生素（诺氟沙星、环丙沙星和N-脱甲基氧氟沙星）合成了共轭物。某些吡咯菌素-氟喹诺酮共轭物在一些铜绿假单胞菌菌株的生长抑制实验中展现出了抗菌活性。然而，这些活性弱于单一抗生素。这些特性似乎与共轭物的溶解性和生物利用度以及所用接头臂的稳定性有关。