losartan N₂-D-glucuronide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: losartan N₂-D-glucuronide
• 英文别名: losartan-N2-glucuronide；(2S,3S,4S,5R)-6-[5-[2-[4-[[2-butyl-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]phenyl]tetrazol-2-yl]-3,4,5-trihydroxyoxane-2-carboxylic acid
• 化学式: C₂₈H₃₁ClN₆O₇
• 分子量: 599.043
• InChiKey: NGFMQMUIOUSHGR-JNKBPBDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  189
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  洛沙坦 、 uridine-5'-diphospho-α-D-glucuronic acid trisodium salt 在 磷酸 作用下， 反应 5.0h， 以7.4%的产率得到losartan N₂-D-glucuronide
  参考文献：
  名称：

  Enzyme-assisted synthesis and structure characterization of glucuronic acid conjugates of losartan, candesartan, and zolarsartan

  摘要：

  Three angiotensin II receptor antagonists-losartan, candesartan, and zolarsartan-were investigated. All the compounds, which are structural analogues, are metabolized via conjugation to glucuronic acid. Interestingly, both O- and N-glucuronidation take place, so that regioisomers are formed. One ether O-glucuronide, two acyl O-glucuronides, and five tetrazole-N-glucuronides were biosynthesized, in milligram scale, from the three sartan aglycones. Liver microsomes from bovine, moose, rat, and pig and recombinant human UDP-glucuronosyltransferases were used as catalysts. The synthesized compounds were identified as sartan glucuronides by mass spectrometry, while the sites of glucuronidation were determined by nuclear magnetic resonance spectroscopy. Drug metabolites are needed as standards for pharmaceutical research and, as the present study shows, they can easily be produced with enzymes as catalyst. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2008.02.004

文献信息

• Enzyme-assisted synthesis and structure characterization of glucuronic acid conjugates of losartan, candesartan, and zolarsartan
  作者：Anna Alonen、Johanna Jansson、Sirkku Kallonen、Alexandros Kiriazis、Olli Aitio、Moshe Finel、Risto Kostiainen

  DOI：10.1016/j.bioorg.2008.02.004

  日期：2008.6

  Three angiotensin II receptor antagonists-losartan, candesartan, and zolarsartan-were investigated. All the compounds, which are structural analogues, are metabolized via conjugation to glucuronic acid. Interestingly, both O- and N-glucuronidation take place, so that regioisomers are formed. One ether O-glucuronide, two acyl O-glucuronides, and five tetrazole-N-glucuronides were biosynthesized, in milligram scale, from the three sartan aglycones. Liver microsomes from bovine, moose, rat, and pig and recombinant human UDP-glucuronosyltransferases were used as catalysts. The synthesized compounds were identified as sartan glucuronides by mass spectrometry, while the sites of glucuronidation were determined by nuclear magnetic resonance spectroscopy. Drug metabolites are needed as standards for pharmaceutical research and, as the present study shows, they can easily be produced with enzymes as catalyst. (C) 2008 Elsevier Inc. All rights reserved.