1-甲基-5-((3-(3-(1-哌啶基甲基)苯氧基)丙基)氨基)-1H-1,2,4-三唑-3-羧酸 | 80343-52-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-甲基-5-((3-(3-(1-哌啶基甲基)苯氧基)丙基)氨基)-1H-1,2,4-三唑-3-羧酸
• 中文别名: 苯磺酸,4-氯-2-羟基-,盐(1:1)钠
• 英文名称: 1-methyl-5-[[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amino]-1H-1,2,4-triazole-3-carboxylic acid
• 英文别名: 1-Methyl-5-((3-(3-(1-piperidinylmethyl)phenoxy)propyl)amino)-1H-1,2,4-triazole-3-carboxylic acid；1-methyl-5-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1,2,4-triazole-3-carboxylic acid
• CAS: 80343-52-8
• 化学式: C₁₉H₂₇N₅O₃
• 分子量: 373.455
• InChiKey: FVXKKIQNOGUXPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  92.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  酒石酸 、 1-甲基-5-((3-(3-(1-哌啶基甲基)苯氧基)丙基)氨基)-1H-1,2,4-三唑-3-羧酸 在 氯化亚砜 作用下， 以 N-甲基乙酰胺 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 生成 1-Methyl-5-[[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amino]-1H-1,2,4-triazole-3-carboxamide tartrate dihydrate
  参考文献：
  名称：

  Triazole amine compounds, their pharmaceutical compositions and method

  摘要：

  该发明提供了一般式（I）的化合物##STR1##及其生理上可接受的盐、水合物和生物前体，在其中取代基在详细描述中定义。这些化合物显示了作为选择性组织胺H.sub.2受体拮抗剂的药理活性。

  公开号：

  US04670448A1
• 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 3-(1-哌啶基甲基)苯酚 、 3-[3-(哌啶-1-基甲基)苯氧基]丙酸 、 1-甲基-5-((3-(3-(1-哌啶基甲基)苯氧基)丙基)氨基)-1H-1,2,4-三唑-3-羧酸 、 loxtidine glucuronide
  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

• US4670448A
  申请人：——

  公开号：US4670448A

  公开（公告）日：1987-06-02
• Triazole amine compounds, their pharmaceutical compositions and method
  申请人：Glaxo Group Limited

  公开号：US04670448A1

  公开（公告）日：1987-06-02

  The invention provides compounds of the general formula (I) ##STR1## and physiologically acceptable salts, hydrates and bioprecursors thereof, in which the substituents are defined in the detailed description. The compounds show pharmaceutical activity as selective histamine H.sub.2 -antagonists.

  该发明提供了一般式（I）的化合物##STR1##及其生理上可接受的盐、水合物和生物前体，在其中取代基在详细描述中定义。这些化合物显示了作为选择性组织胺H.sub.2受体拮抗剂的药理活性。
• 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.