氟哌啶醇葡糖苷酸 | 100442-88-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 氟哌啶醇葡糖苷酸
• 中文别名: 氟哌啶醇-β-D-葡萄糖醛酸；氟哌啶醇-Β-D-葡萄糖醛酸苷
• 英文名称: Haloperidol O-glucuronide
• 英文别名: haloperidol β-glucuronide；Haloperidol Glucuronide；(2S,3S,4S,5R,6S)-6-[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 100442-88-4
• 化学式: C₂₇H₃₁ClFNO₈
• 分子量: 551.996
• InChiKey: ZFNLYKVTHNLKNZ-AMWBNRJOSA-N

物化性质

• 熔点：
  180-182°C
• 沸点：
  754.2±60.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二甲基亚砜、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  氟哌啶醇 、 6-[[[5-(2,4-二氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-3,4,5-三羟基四氢吡喃-2-羧酸 在 UDP-glucuronosyltransferase in rat liver microsomes 、 magnesium chloride 作用下， 以 甲醇 为溶剂， 反应 0.33h， 生成 氟哌啶醇葡糖苷酸
  参考文献：
  名称：

  Glucuronidation of haloperidol by rat liver microsomes: involvement of family 2 UDP-glucuronosyltransferases

  摘要：

  The purposes of this study were to develop a HPLC method to assay for haloperidol glucuronide (HALG); to apply this assay method to the in vitro determination of haloperidol (HAL) UDP-glucuronosyltransferase (UGT) enzyme kinetics in rat liver microsomes (RLM); and to identify the UGT isoforms catalyzing glucuronidation of HAL in rats. Incubation of Brij-activated RLM with HAL and UDP-glucuronic acid (UDPGA) in TRIS pH 7.4 buffer resulted in the formation of a single peak in the HPLC chromatogram at 270 nm. The identity of this peak was confirmed to be that of HALG by 1) beta-glucuronidase hydrolysis; 2) incubation without UDPGA; 3) UV spectral analysis; and 4) LC/MS/MS to yield the expected mass of 552.1. Enzyme kinetic studies using single enzyme Michaelis-Menton model showed an apparent V-max = 271.9 +/- 10.1 pmoles min(-1) mg protein(-1) and K-m = 61 +/- 7.2 muM. Glucuronidation activity in homozygous Gunn j/j) rats was approximately 80% as compared to Sprague-Dawley RLM. HALG formation was approximately doubled in PB-induced RLM. There was no increase in glucuronidation activities in 3MC-induced RLM. The Gunn rat and the PB-induced RLM data suggest predominant but not exclusive involvement of the UGT2B family in the formation of HALG. Because the UGTs exhibit overlapping substrate specificities and most substrates are glucuronidated by more than one isoform, inhibition studies with UGT2B1 substrate probe testosterone and the UGT2B12 substrate probe borneol were conducted. UGT2B1 and UGT2B12 exhibited 40% and 90% inhibition of HAL glucuronidation, respectively. Thus, UGT2B12 and UGT2B1 isoforms are responsible for catalyzing HAL glucuronidation in rats. Our HPLC assay provides a specific and sensitive technique for the measurement of in vitro HAL-UGT activity. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.lfs.2003.10.009