7-(4-hexadecanoyl-piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid | 1186385-05-6

• 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-hexadecanoyl-piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
• 英文别名: 7-(4-hexadecanoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid；1-Cyclopropyl-6-fluoro-7-(4-hexadecanoylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
• CAS: 1186385-05-6
• 化学式: C₃₃H₄₈FN₃O₄
• 分子量: 569.76
• InChiKey: XUVBDBWTYVPRGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  环丙沙星 、 棕榈酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以58%的产率得到7-(4-hexadecanoyl-piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: Synthesis and in vitro biological evaluation as potential antitumor agents

  摘要：

  Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC50 values ranging from mu M to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC50 values were <= 10 mu M in three (derivative 2) or four (derivative 6h) cancer cell lines. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.053

文献信息

• Anticancer and antimicrobial effects of novel ciprofloxacin fatty acids conjugates
  作者：Alicja Chrzanowska、Piotr Roszkowski、Anna Bielenica、Wioletta Olejarz、Karolina Stępień、Marta Struga

  DOI：10.1016/j.ejmech.2019.111810

  日期：2020.1

  cell line was the most sensitive to the presence of the obtained conjugates. The value of IC50 for oleic acid conjugate (4) was 7.7 μM, and it was 12 times lower than for CP alone (101.4 μM). The studied derivatives induced late apoptosis in all cancer cell lines, but not in normal cells. The most potent apoptosis inducer was conjugate 4, that resulted in the highest percentage of PC3 cells in late

  环丙沙星（CP）对某些癌细胞具有确定的细胞毒性作用，但浓度高且无药理学作用。考虑到天然脂肪酸的特性，例如生物相容性，生物降解性以及癌细胞对细胞吸收的增加，似乎将它们与药物结合可以改善其生物利用度，从而改善细胞毒性。因此，本研究的目的是将CP与饱和和不饱和脂肪酸偶联，并评估它们在人原发性（SW480）和转移性（SW620）结肠癌，转移性癌中的细胞毒性，凋亡诱导作用以及IL-6释放的抑制作用。前列腺癌（PC3）和正常（HaCaT）细胞系。PC3细胞系对获得的结合物最敏感。油酸共轭物（4）的IC50值为7.7μM，比单独的CP（101.4μM）低12倍。研究的衍生物在所有癌细胞系中诱导晚期凋亡，但在正常细胞中不诱导。最有效的凋亡诱导剂是缀合物4，其在晚期凋亡中导致PC3细胞的百分比最高（81.5％±3.9），其次是花生油酰胺5（75％±4.8）。DHA（8）和山梨酸（2）酸的结合物显示出对SW4
• Fluoroquinolones and use thereof to treat bacterial infections
  申请人：UNIVERSITÉ PIERRE ET MARIE CURIE—PARIS 6 (UPMC)

  公开号：US10087165B2

  公开（公告）日：2018-10-02

  The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.

  本发明涉及新型氟喹诺酮类药物、药物组合物或含有它们的药物以及使用它们治疗细菌感染。
• NOVEL FLUOROQUINOLONES AND USE THEREOF TO TREAT BACTERIAL INFECTIONS
  申请人：Université Pierre et Marie Curie - Paris 6 (UPMC)

  公开号：EP3157911A1

  公开（公告）日：2017-04-26
• [EN] NOVEL FLUOROQUINOLONES AND USE THEREOF TO TREAT BACTERIAL INFECTIONS<br/>[FR] NOUVEAUX FLUOROQUINOLONES ET LEUR UTILISATION POUR TRAITER DES INFECTIONS BACTÉRIENNES
  申请人：UNIVERSITÉ PIERRE ET MARIE CURIE PARIS 6 UPMC

  公开号：WO2015193454A1

  公开（公告）日：2015-12-23

  The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.
• 7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: Synthesis and in vitro biological evaluation as potential antitumor agents
  作者：Joëlle Azéma、Brigitte Guidetti、Janique Dewelle、Benjamin Le Calve、Tatjana Mijatovic、Alexander Korolyov、Julie Vaysse、Myriam Malet-Martino、Robert Martino、Robert Kiss

  DOI：10.1016/j.bmc.2009.06.053

  日期：2009.8

  Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC50 values ranging from mu M to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC50 values were <= 10 mu M in three (derivative 2) or four (derivative 6h) cancer cell lines. (C) 2009 Elsevier Ltd. All rights reserved.