candesartan-O-glucuronide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: candesartan-O-glucuronide
• 英文别名: Candesartan O-glucuronide；(2S,3S,4S,5R)-6-[2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• 化学式: C₃₀H₂₈N₆O₉
• 分子量: 616.587
• InChiKey: IQMPSFXZXNRDMY-GPKAUORGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  215
• 氢给体数：
  5
• 氢受体数：
  13

ADMET

代谢

(2S,3S,4S,5R)-6-[2-乙氧基-3-[[4-[2-(2H-四唑-5-基)苯基]苯基]甲基]苯并咪唑-4-羰基]氧基-3,4,5-三羟基氧杂环戊烷-2-羧酸是坎地沙坦已知的人体代谢物。

(2S,3S,4S,5R)-6-[2-Ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid is a known human metabolite of Candesartan.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  坎地沙坦 、 uridine-5'-diphospho-α-D-glucuronic acid trisodium salt 在 saccharic acid-1,4-lactone 、 recombinant human UDP-glucuronyltransferase 1A₈ 作用下， 反应 48.0h， 以7.4%的产率得到candesartan-O-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