(S)-10-(4-ethylpiperazin-1-yl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid

• 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: (S)-10-(4-ethylpiperazin-1-yl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
• 英文别名: (S)-(-)-9-Fluoro-3-Methyl-10-(4-Ethyl-1-Piperazinyl)-7-Oxo-2,3-Dihydro-7H-Pyrido[1,2,3-de][1,4]Benzoxazine-6-Carboxylic Acid；Levofloxacin impurity 23；(2S)-6-(4-ethylpiperazin-1-yl)-7-fluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
• 化学式: C₁₉H₂₂FN₃O₄
• 分子量: 375.4
• InChiKey: JFUHXTFZSVKCSK-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  左旋氧氟沙星羧酸 生成 (S)-10-(4-ethylpiperazin-1-yl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
  参考文献：
  名称：

  XAYAKAVA, ISAO;SINKO, SEGO;JOKOXAMA, KEHJITI

  摘要：

  DOI：

文献信息

• Nano-Fe3O4@ZrO2-SO3H as Highly Efficient Recyclable Catalyst for the Green Synthesis of Fluoroquinolones
  作者：Ahmad Nakhaei、Shirin Ramezani、Sayyed Jalal Shams-Najafi、Sadaf Farsinejad

  DOI：10.2174/1570178615666171226162735

  日期：2018.7.26

  showed good catalytic performance in the both forms of water. However, the magnetized water showed better results. Therefore, this new procedure provides prompt achievement to the appropriate products with acceptable yields in water as a green solvent at reflux situations with an easy work‐up process. Furthermore, the catalyst was recyclable and could be reused at least three times without any discernible

  已经制备了带有磺酸基团的核壳氧化锆包覆磁铁矿纳米颗粒（纳米-Fe3O4@ZrO2-H3PO4），并将其用作一种有效的酸催化剂，用于通过 7-卤代-6 氟喹诺酮-3 羧酸与各种哌嗪衍生物和 (4aR,7aR)-八氢-1H-吡咯并[3,4-b] 吡啶。反应在普通水或磁化水作为溶剂中进行。在最终结果中，纳米 Fe3O4@ZrO2-SO3H 在两种形式的水中都表现出良好的催化性能。然而，磁化水显示出更好的结果。因此，这种新方法在回流条件下，在作为绿色溶剂的水中以可接受的收率和简单的后处理过程迅速实现了合适的产品。此外，
• Effect of N-1/C-8 Ring Fusion and C-7 Ring Structure on Fluoroquinolone Lethality
  作者：Muhammad Malik、Kevin R. Marks、Heidi A. Schwanz、Nadezhda German、Karl Drlica、Robert J. Kerns

  DOI：10.1128/aac.01054-10

  日期：2010.12

  Quinolones rapidly kill bacteria by two mechanisms, one that requires protein synthesis and one that does not. The latter, which is measured as lethal action in the presence of the protein synthesis inhibitor chloramphenicol, is enhanced by N-1 cyclopropyl and C-8 methoxy substituents, as seen with the highly lethal compound PD161144. In some compounds, such as levofloxacin, the N-1 and C-8 substituents are fused. To assess the effect of ring fusion on killing, structural derivatives of levofloxacin and PD161144 differing at C-7 were synthesized and examined with Escherichia coli . A fused-ring derivative of PD161144 exhibited a striking absence of lethal activity in the presence of chloramphenicol. In general, ring fusion had little effect on lethal activity when protein synthesis was allowed, but fusion reduced lethal activity in the absence of protein synthesis to extents that depended on the C-7 ring structure. Additional fused-ring fluoroquinolones, pazufloxacin, marbofloxacin, and rufloxacin, also exhibited reduced activity in the presence of chloramphenicol. Energy minimization modeling revealed that steric interactions of the trans -oriented N-1 cyclopropyl and C-8 methoxy moieties skew the quinolone core, rigidly orient these groups perpendicular to core rings, and restrict the rotational freedom of C-7 rings. These features were not observed with fused-ring derivatives. Remarkably, structural effects on quinolone lethality were not explained by the recently described X-ray crystal structures of fluoroquinolone-topoisomerase IV-DNA complexes, suggesting the existence of an additional drug-binding state.

  摘要 喹诺酮类药物通过两种机制迅速杀死细菌，一种需要蛋白质合成，另一种不需要。后者是指在蛋白质合成抑制剂氯霉素存在时的致死作用，N-1 环丙基和 C-8 甲氧基取代基增强了这种作用，高致死性化合物 PD161144 就具有这种作用。在某些化合物（如左氧氟沙星）中，N-1 和 C-8 取代基融合在一起。为了评估环融合对杀伤力的影响，我们合成了左氧氟沙星和 PD161144 在 C-7 处不同的结构衍生物，并用大肠杆菌进行了检测。 大肠杆菌 .PD161144 的一种环状融合衍生物在氯霉素存在的情况下明显缺乏致死活性。一般来说，在允许蛋白质合成的情况下，环融合对致死活性的影响很小，但在没有蛋白质合成的情况下，融合会降低致死活性，其程度取决于 C-7 环结构。其他融合环氟喹诺酮类药物帕珠沙星、马波沙星和芦氟沙星在氯霉素存在的情况下也表现出活性降低。能量最小化模型显示，反式氟哌酸和环氟哌酸的立体相互作用会导致活性降低。 反式 -N-1 环丙基和 C-8 甲氧基的立体相互作用使喹诺酮核心偏斜，使这些基团垂直于核心环刚性定向，并限制了 C-7 环的旋转自由度。在融合环衍生物中没有观察到这些特征。值得注意的是，最近描述的氟喹诺酮-拓扑异构酶 IV-DNA 复合物的 X 射线晶体结构无法解释结构对喹诺酮致死性的影响，这表明还存在另一种药物结合态。
• Conventional and microwave-assisted synthesis of quinolone carboxylic acid derivatives
  作者：Y. Mirzaie、J. Lari、H. Vahedi、M. Hakimi

  DOI：10.1134/s1070363216120525

  日期：2016.12

  Various antibacterial fluoroquinolone compounds are synthesized by the direct amination of 7-halo-6-fluoroquinolone-3-carboxylic acids with a variety of piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b]pyridine using microwave under different reaction conditions. Solvent free high yield microwave synthesis of antibacterial fluoroquinolone compounds is convenient, rapid and environmentally friendly method.
• Optically active pyridobenzoxazine derivatives
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0206283B1

  公开（公告）日：1993-01-27
• XAYAKAVA, ISAO;SINKO, SEGO;JOKOXAMA, KEHJITI
  作者：XAYAKAVA, ISAO、SINKO, SEGO、JOKOXAMA, KEHJITI

  DOI：——

  日期：——