4-羟基吡喹酮 | 60743-58-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 4-羟基吡喹酮
• 中文别名: 2-(4-羟基环己烷羰基)-2,3,6,7-四氢-1H-吡嗪并[2,1-A]异喹啉-4(11BH)-酮
• 英文名称: 4-hydroxyl-praziquantel
• 英文别名: 4'-hydroxypraziquantel；4-hydroxyl-PZQ；2-(4-hydroxy-cyclohexanecarbonyl)-1,2,3,6,7,11b-hexahydro-pyrazino[2,1-a]isoquinolin-4-one；trans-Hydroxy Praziquantel；2-(4-hydroxycyclohexanecarbonyl)-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one
• CAS: 60743-58-0
• 化学式: C₁₉H₂₄N₂O₃
• 分子量: 328.411
• InChiKey: OKTGUGBZQBTMHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  吡喹酮 在 盐酸 、 对甲苯磺酸 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 53.0h， 生成 4-羟基吡喹酮
  参考文献：
  名称：

  一种吡喹酮代谢产物的合成方法

  摘要：

  本发明涉及两种吡喹酮的代谢产物的合成方法，属于药物技术领域，分别以吡喹酮和4‑羟基环己烷甲酸甲酯为原料，吡喹酮和环己烯‑3‑甲酸为原料合成吡喹酮的两种代谢产物。其优点表现在：本发明首次合成了吡喹酮的这两种代谢产物。并且，这两种吡喹酮代谢产物的合成工艺简单，获得的产物纯度高。

  公开号：

  CN105061424B

文献信息

• Identification of human cytochrome P 450 s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data
  作者：Xue-Qing Li、Anders Bj�rkman、Tommy B. Andersson、Lars L. Gustafsson、Collen M. Masimirembwa

  DOI：10.1007/s00228-003-0636-9

  日期：2003.9.1

  Objective. Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P-450 (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vivo drug clearances from in vitro data.Methods. In vitro systems, rat and human liver microsomes (RLM, HLM) and recombinant cytochrome P-450 (rCYP), were used to determine the intrinsic clearance (CLint) and identify responsible CYPs and their relative contribution in the metabolism of 15 commonly used APDs.Results and discussion. CLint determined in RLM and HLM showed low (r(2)=0.50) but significant (P<0.01) correlation. The CLint values were scaled to predict in vivo hepatic clearance (CLH) using the 'venous equilibrium model'. The number of compounds with in vivo human CL data after intravenous administration was low (n=8), and the range of CL values covered by these compounds was not appropriate for a reasonable quantitative in vitro-in vivo correlation analysis. Using the CLH predicted from the in vitro data, the compounds could be classified into three different categories: high-clearance drugs (>70% liver blood flow; amodiaquine, praziquantel, albendazole, thiabendazole), low-clearance drugs (<30% liver blood flow; chloroquine, dapsone, diethylcarbamazine, pentamidine, primaquine, pyrantel, pyrimethamine, tinidazole) and intermediate clearance drugs (artemisinin, artesunate, quinine). With the exception of artemisinin, which is a high clearance drug in vivo, all other compounds were classified using in vitro data in agreement with in vivo observations. We identified hepatic CYP enzymes responsible for metabolism of some compounds (praziquantel-1A2, 2C19, 3A4; primaquine-1A2, 3A4; chloroquine-2C8, 2D6, 3A4; artesunate-2A6; pyrantel-2D6). For the other compounds, we confirmed the role of previously reported CYPs for their metabolism and identified other CYPs involved which had not been reported before.Conclusion. Our results show that it is possible to make in vitro-in vivo predictions of high, intermediate and low CLint drug categories. The identified CYPs for some of the drugs provide a basis for how these drugs are expected to behave pharmacokinetically and help in predicting drug-drug interactions in vivo.
• KIEC-KONONOWICZ, KATARZYNA;FARGHALY, ZINAB S.;BLASCHKE, GOTTFRIED, ARCH. PHARM., 324,(1991) N, C. 235-237
  作者：KIEC-KONONOWICZ, KATARZYNA、FARGHALY, ZINAB S.、BLASCHKE, GOTTFRIED

  DOI：——

  日期：——