(5-methyl-3-phenyl-isoxazol-4-yl)-penicillin | 740789-23-5

• 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
• 英文名称: (5-methyl-3-phenyl-isoxazol-4-yl)-penicillin
• 英文别名: oxacillin；Oxazillin；3,3-Dimethyl-6-[(5-methyl-3-phenyl-1,2-oxazole-4-carbonyl)amino]-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 740789-23-5
• 化学式: C₁₉H₁₉N₃O₅S
• 分子量: 401.443
• InChiKey: UWYHMGVUTGAWSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (5-methyl-3-phenyl-isoxazol-4-yl)-penicillin 生成 penicilloic acid 、 2-{Carboxy-[(5-hydroxymethyl-3-phenyl-isoxazole-4-carbonyl)-amino]-methyl}-5,5-dimethyl-thiazolidine-4-carboxylic acid 、 5-hydroxymethyl derivative of oxacillin
  参考文献：
  名称：

  High performance liquid chromatographic analysis and pharmacokinetic investigation of oxacillin and its metabolites in man.

  摘要：

  Pharmacokinetic evaluation of oxacillin in man was carried out by detailed investigation of the urinary excretion profiles of unchanged oxacillin and metabolites. A new metabolite, penicilloic acid of the 5-hydroxymethyl derivative of oxacillin, was discovered in human urine excreted after oral administration of oxacillin. This metabolite was formed by cleavage of the β-lactam ring of the 5-hydroxymethyl derivative (a known active metabolite of oxacillin), not by hydroxylation of the 5-methyl group on the isoxazolyl moiety of penicilloic acid of oxacillin. The time courses of excretion of the new metabolite as well as unchanged oxacillin and known metabolites (penicilloic acid and 5-hydroxymethyl derivative) were measured by HPLC analysis of urine excreted after oral administration of oxacillin tablets to human subjects. The values for cumulative excretion amount at infinite time (X∞) and mean residence time (MRT) for each species were estimated by moment analysis of excretion rate vs. time curves. The rate constants for absorption, metabolism, and urinary excretion were calculated by non-linear least-squares fittings of the time course data using a one compartment model. The results indicate that the excretion ratio (X∞/D, D=500 mg) and MRT value as averages of five subjects are 27.4% and 1.76 h for unchanged oxacillin, 16.1% and 3.79 h for penicilloic acid, 22.2% and 2.04 h for 5-hydroxymethyl derivative, and 22.4% and 3.89 h for penicilloic acid of the 5-hydroxymethyl derivative. The conversion ratio at each elimination step and the MRT value intrinsic to each metabolite were evaluated from the results of moments.

  DOI：

  10.1248/cpb.29.3290

文献信息

• [EN] IMPROVED PROCESS FOR PREPARING PENICILLINS AND INTERMEDIATE COMPOUNDS<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE PÉNICILLINES ET AUTRES COMPOSÉS INTERMÉDIAIRES
  申请人：VARDHMAN CHEMTECH LTD

  公开号：WO2012164355A1

  公开（公告）日：2012-12-06

  Disclosed is an improved process for the preparation of isoxazolyl penicillins of formula (I), wherein X1 and X2 can be independently selected from the group comprising hydrogen, chlorine or fluorine, and its pharmaceutically suitable salts. The process is economic in -situ synthetic method without isolation of any intermediate. (I).

  公开了一种改进的制备式(I)异噁唑基青霉素的方法，其中X1和X2可以独立地选择自氢、氯或氟的群体，以及其药用盐。该方法是一种经济的原位合成方法，无需分离任何中间体。(I)。