(3S)-6-[(decanoyloxy)methyl] 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate | 1261134-58-0

• 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: (3S)-6-[(decanoyloxy)methyl] 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate
• 英文别名: decanoyloxymethyl (2S)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylate
• CAS: 1261134-58-0
• 化学式: C₂₉H₄₀FN₃O₆
• 分子量: 545.652
• InChiKey: DAMRFXIRQHSRIB-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  88.6
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  左氧氟沙星 、 癸酸氯甲酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.33h， 以79%的产率得到(3S)-6-[(decanoyloxy)methyl] 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate
  参考文献：
  名称：

  Novel lipophilic 7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid derivatives as potential antitumor agents: Improved synthesis and in vitro evaluation

  摘要：

  A convenient route for the synthesis of some acyloxymethyl esters and carboxamides of levofloxacin (LV) with modulated lipophilicity is described. The synthesized compounds were evaluated in vitro for their growth inhibitory effect in five human cancer cell lines. The most efficient LV derivatives (ester 2e and amide 4d) displayed IC50 values in the 0.2-2.2 mu M range, while IC50 values for parent LV ranged between 70 and 622 mu M depending on the cell line. The esters displayed no in vivo toxicity up to 80 mg/kg when administered intraperitoneally. This study thus shows that LV analogs displayed antitumor efficacy, at least in vitro, a feature that appeared to be independent from the lipophilicity of the grafted substituent. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.039

文献信息

• Novel lipophilic 7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid derivatives as potential antitumor agents: Improved synthesis and in vitro evaluation
  作者：Alexander Korolyov、Sandra Dorbes、Joëlle Azéma、Brigitte Guidetti、Mathieu Danel、Delphine Lamoral-Theys、Thierry Gras、Jacques Dubois、Robert Kiss、Robert Martino、Myriam Malet-Martino

  DOI：10.1016/j.bmc.2010.10.039

  日期：2010.12

  A convenient route for the synthesis of some acyloxymethyl esters and carboxamides of levofloxacin (LV) with modulated lipophilicity is described. The synthesized compounds were evaluated in vitro for their growth inhibitory effect in five human cancer cell lines. The most efficient LV derivatives (ester 2e and amide 4d) displayed IC50 values in the 0.2-2.2 mu M range, while IC50 values for parent LV ranged between 70 and 622 mu M depending on the cell line. The esters displayed no in vivo toxicity up to 80 mg/kg when administered intraperitoneally. This study thus shows that LV analogs displayed antitumor efficacy, at least in vitro, a feature that appeared to be independent from the lipophilicity of the grafted substituent. (C) 2010 Elsevier Ltd. All rights reserved.