(5-氨基-1-甲基-1,2,4-三唑-3-基)甲醇 | 90359-00-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (5-氨基-1-甲基-1,2,4-三唑-3-基)甲醇
• 英文名称: 5-Amino-1-methyl-1H-1,2,4-triazole-3-methanol
• 英文别名: (5-amino-1-methyl-1,2,4-triazol-3-yl)methanol
• CAS: 90359-00-5
• 化学式: C₄H₈N₄O
• 分子量: 128.134
• InChiKey: NQDFUNABLVGWTB-UHFFFAOYSA-N

物化性质

• 沸点：
  385.5±44.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  拉伏替丁 在 hepatocytes 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 (5-氨基-1-甲基-1,2,4-三唑-3-基)甲醇 、
  参考文献：
  名称：

  Utility of hepatocytes to model species differences in the metabolism of loxtidine and to predict pharmacokinetic parameters in rat, dog and man

  摘要：

  1. The metabolism of loxtidine (1-methyl-5-[3-[3-[(1-piperidinyl) methyl] phenoxy] propyl] amino-1H-1,2,4-triazole-3-methanol) was studied in freshly isolated rat, dog and human hepatocytes. Metabolism in vitro was comparable with previously available in vivo data in all three species with the marked species differences observed in vivo being reproduced in the hepatocyte model.2. The major route for the metabolism of loxtidine by rat hepatocytes was N-dealkylation to form the propionic acid and hydroxymethyl triazole metabolites. A minor metabolic route was the oxidation of loxtidine to a carboxylic acid metabolite. The major route of metabolism for loxtidine in dog hepatocytes was glucuronidation with oxidation to the carboxylic acid metabolite being of minor importance. Incubation of loxtidine with human hepatocytes resulted in the drug remaining largely unchanged but with the carboxylic acid metabolite being produced in minor amounts.3. In vitro studies were undertaken with rat, dog and human hepatocytes to determine the Michaelis-Menten parameters V-max and K-m for the sum of all the metabolic pathways. These kinetic parameters were used to calculate the intrinsic clearance of loxtidine. Using appropriate scaling factors, the predicted in vivo hepatic clearance was then calculated. The predicted intrinsic clearances were 51.4+/-12.4, 8.0+/-0.8 and 1.0+/-0.6 ml/min/kg for rat, dog and human hepatocytes respectively. These data were then used to calculate hepatic clearances of 24.5, 3.1 and 0.2 ml/min/kg for rat, dog and man respectively.4. In vivo hepatic and intrinsic clearances for loxtidine were determined in rat, dog and human volunteers. The hepatic clearances of loxtidine were 26.6, 6.6 and 0.4 ml/min/kg in rat, dog and man respectively and intrinsic clearances were 58.5, 18.5 and 2.0 ml/min/kg in rat, dog and man respectively.5. The present studies demonstrate that the hepatocyte model map be a valuable in vitro tool for predicting both qualitative and quantitative aspects of the metabolism of a drug in animals and man at an early stage of the drug development process.

  DOI：

  10.1080/004982599238650

文献信息

• Utility of hepatocytes to model species differences in the metabolism of loxtidine and to predict pharmacokinetic parameters in rat, dog and man
  作者：M. K. BAYLISS

  DOI：10.1080/004982599238650

  日期：1999.1

  1. The metabolism of loxtidine (1-methyl-5-[3-[3-[(1-piperidinyl) methyl] phenoxy] propyl] amino-1H-1,2,4-triazole-3-methanol) was studied in freshly isolated rat, dog and human hepatocytes. Metabolism in vitro was comparable with previously available in vivo data in all three species with the marked species differences observed in vivo being reproduced in the hepatocyte model.2. The major route for the metabolism of loxtidine by rat hepatocytes was N-dealkylation to form the propionic acid and hydroxymethyl triazole metabolites. A minor metabolic route was the oxidation of loxtidine to a carboxylic acid metabolite. The major route of metabolism for loxtidine in dog hepatocytes was glucuronidation with oxidation to the carboxylic acid metabolite being of minor importance. Incubation of loxtidine with human hepatocytes resulted in the drug remaining largely unchanged but with the carboxylic acid metabolite being produced in minor amounts.3. In vitro studies were undertaken with rat, dog and human hepatocytes to determine the Michaelis-Menten parameters V-max and K-m for the sum of all the metabolic pathways. These kinetic parameters were used to calculate the intrinsic clearance of loxtidine. Using appropriate scaling factors, the predicted in vivo hepatic clearance was then calculated. The predicted intrinsic clearances were 51.4+/-12.4, 8.0+/-0.8 and 1.0+/-0.6 ml/min/kg for rat, dog and human hepatocytes respectively. These data were then used to calculate hepatic clearances of 24.5, 3.1 and 0.2 ml/min/kg for rat, dog and man respectively.4. In vivo hepatic and intrinsic clearances for loxtidine were determined in rat, dog and human volunteers. The hepatic clearances of loxtidine were 26.6, 6.6 and 0.4 ml/min/kg in rat, dog and man respectively and intrinsic clearances were 58.5, 18.5 and 2.0 ml/min/kg in rat, dog and man respectively.5. The present studies demonstrate that the hepatocyte model map be a valuable in vitro tool for predicting both qualitative and quantitative aspects of the metabolism of a drug in animals and man at an early stage of the drug development process.