2-γ-[(p-fluorobenzyl-ol)propyl]-1,2,3,4,6,7,12,12a-octahydropyrazino(2',1':6,1)pyrido[3,4-b]indole | 41510-24-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-γ-[(p-fluorobenzyl-ol)propyl]-1,2,3,4,6,7,12,12a-octahydropyrazino(2',1':6,1)pyrido[3,4-b]indole
• 英文别名: 1-(4-fluoro-phenyl)-4-(3,4,6,7,12,12a-hexahydro-1H-pyrazino[1',2':1,6]pyrido[3,4-b]indol-2-yl)-butan-1-ol；1-(4-fluorophenyl)-4-[(8S)-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-6-yl]butan-1-ol
• CAS: 41510-24-1
• 化学式: C₂₄H₂₈FN₃O
• 分子量: 393.504
• InChiKey: JMVWLBXXTJHCFV-XGLRFROISA-N

物化性质

• 沸点：
  597.7±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  42.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  比立哌隆 在 sodium tetrahydroborate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 0.25h， 生成 2-γ-[(p-fluorobenzyl-ol)propyl]-1,2,3,4,6,7,12,12a-octahydropyrazino(2',1':6,1)pyrido[3,4-b]indole
  参考文献：
  名称：

  Metabolism and excretion of centbutindole (neuroleptic) in rats after oral administration

  摘要：

  摘要：对Sprague-Dawley大鼠进行口服给药后，研究了centbutindole的代谢和排泄。在4天内监测了排泄的剂量百分比。还努力评估了centbutindole在各种体外生物基质中的稳定性。发现centbutindole在大鼠中被代谢，只有微量的母药被排泄。胆汁和粪便中排泄的剂量百分比分别为0.2%和0.6%。口服给药后尿液中未检测到药物，但静脉注射后，仅有0.0012%的剂量通过尿液排泄。通过离子喷雾LC/MS/MS鉴定了两种代谢物，去烷基化代谢物和羟基代谢物，使用了母离子和产物离子扫描技术。Centbutindole的代谢主要途径包括还原丁酰苯酮侧链中的羰基官能团以及连接到吡啶吡啶吡哌啶环氮原子位置2的丁酰苯酮侧链的N-去烷基化。羟基代谢物在胆汁中排泄微量，尽管在其自由形式中与糖醛酸盐结合形式相比更多。

  DOI：

  10.1211/002235702324

文献信息

• Metabolism and excretion of centbutindole (neuroleptic) in rats after oral administration
  作者：M Issar、S K Singh、K P Madhusudanan、B Mishra、R C Gupta

  DOI：10.1211/002235702324

  日期：2010.2.18

  The metabolism and excretion of centbutindole was studied in Sprague-Dawley rats after oral administration. The percentage of dose excreted was monitored over 4 days. Efforts were also directed towards evaluating the stability of centbutindole in various in-vitro biomatrices. Centbutindole was found to be metabolised in rats and only a negligible amount of parent drug was excreted. The percentage of the dose excreted in bile and faeces was 0.2% and 0.6%, respectively. No drug was found in urine after oral administration, but after an intravenous dose only 0.0012% of the dose was eliminated through urine. Two metabolites, dealkylated metabolite and hydroxy metabolite, were identified by ion spray LC/MS/MS, using a combination of parent ion and product ion scanning techniques. The major routes of metabolism of centbutindole include reduction of the carbonyl functional group in the butyrophenone side chain and N-dealkylation of the butyrophenone side chain attached to the pyrazinopyridoindole ring nitrogen at position 2. The hydroxy metabolite was excreted negligibly in bile, although it was present in the form of glucuronide conjugates more in comparison to its free form.

  摘要：对Sprague-Dawley大鼠进行口服给药后，研究了centbutindole的代谢和排泄。在4天内监测了排泄的剂量百分比。还努力评估了centbutindole在各种体外生物基质中的稳定性。发现centbutindole在大鼠中被代谢，只有微量的母药被排泄。胆汁和粪便中排泄的剂量百分比分别为0.2%和0.6%。口服给药后尿液中未检测到药物，但静脉注射后，仅有0.0012%的剂量通过尿液排泄。通过离子喷雾LC/MS/MS鉴定了两种代谢物，去烷基化代谢物和羟基代谢物，使用了母离子和产物离子扫描技术。Centbutindole的代谢主要途径包括还原丁酰苯酮侧链中的羰基官能团以及连接到吡啶吡啶吡哌啶环氮原子位置2的丁酰苯酮侧链的N-去烷基化。羟基代谢物在胆汁中排泄微量，尽管在其自由形式中与糖醛酸盐结合形式相比更多。