5-羟基甲基氟氯西林 | 75524-31-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 5-羟基甲基氟氯西林
• 中文别名: 1-[(E)-(1H-1,2,4-三唑-3-基亚氨基)甲基]-2-萘酚
• 英文名称: 5-Hydroxymethylflucloxacillin
• 英文别名: 5'-hydroxymethylflucloxacillin；5-hydroxymethyl flucloxacillin；(2S,5R,6R)-6-[[3-(2-chloro-6-fluorophenyl)-5-(hydroxymethyl)-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 75524-31-1
• 化学式: C₁₉H₁₇ClFN₃O₆S
• 分子量: 469.878
• InChiKey: ZUBWLMQDPXVIGD-JKIFEVAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  氟氯西林 在 glucose-6-phosphate dehydrogenase 、 glucose-6-phosphate 、 Bacillus megaterium CYP₁₀₂A₁ M₁₁ L₄₃₇E 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 5-羟基甲基氟氯西林
  参考文献：
  名称：

  Characterization of kinetics of human cytochrome P450s involved in bioactivation of flucloxacillin: inhibition of CYP3A-catalysed hydroxylation by sulfaphenazole

  摘要：

  Background and PurposeThe aim of this study was to characterize the human cytochrome P450s (CYPs) involved in oxidative bioactivation of flucloxacillin to 5‐hydroxymethyl flucloxacillin, a metabolite with high cytotoxicity towards biliary epithelial cells.Experimental ApproachThe CYPs involved in hydroxylation of flucloxacillin were characterized using recombinant human CYPs, pooled liver microsomes in the presence of CYP‐specific inhibitors and by correlation analysis using a panel of liver microsomes from 16 donors.Key ResultsRecombinant CYPs showing the highest specific activity were CYP3A4, CYP3A7 and to lower extent CYP2C9 and CTP2C8. Michaelis–Menten enzyme kinetics were determined for pooled human liver microsomes, recombinant CYP3A4, CYP3A7 and CYP2C9. Surprisingly, sulfaphenazole appeared to be a potent inhibitor of 5′‐hydroxylation of flucloxacillin by both recombinant CYP3A4 and CYP3A7.Conclusions and ImplicationsThe combined results show that the 5′‐hydroxylation of flucloxacillin is primarily catalysed by CYP3A4, CYP3A7 and CYP2C9. The large variability of the hepatic expression of these enzymes could affect the formation of 5′‐hydroxymethyl flucloxacillin, which may determine the differences in susceptibility to flucloxacillin‐induced liver injury. Additionally, the strong inhibition in CYP3A‐catalysed flucloxacillin metabolism by sulfaphenazole suggests that unanticipated drug–drug interactions could occur with coadministered drugs.

  DOI：

  10.1111/bph.14548

文献信息

• 19F NMR spectroscopy study of the metabolites of flucloxacillin in rat urine
  作者：J R Everett、K Jennings、G Woodnutt

  DOI：10.1111/j.2042-7158.1985.tb04991.x

  日期：2011.4.12

  19F NMR spectroscopy was used to monitor the metabolites of flucloxacillin in the urine of a rat dosed with its sodium salt. 19F NMR signals were detected and quantified from flucloxacillin and three metabolites. The 19F NMR method involves minimal sample preparation and is free from interference by endogenous urine components. High-field spin-echo 1H NMR spectroscopy and HPLC were used to confirm the results.

  摘要 本研究使用19F NMR光谱技术监测一只被注射了盐酸氟氯西林的大鼠尿液中的代谢物。从氟氯西林和三种代谢物中检测和量化了19F NMR信号。19F NMR方法需要最少的样品处理，并且不受内源性尿液成分的干扰。高场自旋回波1H NMR光谱和HPLC被用来确认结果。