azane,(2S,3S,4S,5R,6R)-6-[[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid | 78132-48-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: azane,(2S,3S,4S,5R,6R)-6-[[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• 英文别名: uridine-diphosphate-glucuronic acid triammonium salt；UDP-glucuronic acid triammonium salt
• CAS: 78132-48-6
• 化学式: C₁₅H₂₂N₂O₁₈P₂*3H₃N
• 分子量: 631.381
• InChiKey: WMWKTCPGFOEPBD-PBSHYCELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.54
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  349.06
• 氢给体数：
  10.0
• 氢受体数：
  17.0

安全信息

• 危险品标志：
  T
• 危险类别码：
  R23/24/25,R36/37/38
• 安全说明：
  S22,S26,S36,S45

反应信息

• 作为反应物：
  描述：

  对硝基苯酚 、 azane,(2S,3S,4S,5R,6R)-6-[[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid 以 水 为溶剂， 反应 0.17h， 生成 4-硝基苯-Β-D-葡萄糖苷酸
  参考文献：
  名称：

  Effects of Ca2+, Zn2+ and Cd2+ on uridine diphosphate-glucuronyltransferase and .BETA.-glucuronidase activities in rat liver microsomes.

  摘要：

  研究了各种金属对大鼠肝脏微粒体中二磷酸尿苷（UDP）-葡糖醛酸转移酶和β-葡糖醛酸酶活性的影响。在酶反应混合物中加入 Mn2+、Cd2+、Zn2+、V5+、Ni2+、Co2+、Cu+ 或 Ca2+（20μM）不会显著改变肝微粒体中 UDP-葡糖醛酸基转移酶的活性。在这些金属中，Zn2+ 和 Cd2+（20μM）能显著提高肝微粒体 β-葡萄糖醛酸酶的活性。Zn2+ 和 Cd2+ 在 5.0 μM 时对β-葡糖醛酸酶活性有明显影响，在 50 μM 时影响达到饱和。Ca2+ （5.0-50 μM）和/或 Ca2+ 结合蛋白雷公藤苷元（2.0 μM）对肝微粒体中的 UDP-葡萄糖醛酸转移酶和 β-葡萄糖醛酸酶活性没有明显影响。因此，Zn2+ 和 Cd2+ 能独特地提高 β-葡糖醛酸酶的活性。Zn2+ 和 Cd2+ 诱导的 β-葡糖醛酸酶活性的增加在存在 SH 基团保护试剂（二硫代苏氨酸）的情况下被完全逆转。经 0.2% Triton X-100 [聚氧乙烯（10）辛基苯基醚]处理后，微粒体酶对 Zn2+ 和 Cd2+ （20 μM）的反应不再出现，这表明这些金属的刺激作用依赖于膜结合。本研究表明，在测试的各种金属中，Zn2+ 和 Cd2+ 能独特地提高肝微粒体 β-葡萄糖醛酸酶的活性，它们的作用是基于与膜上的 SH 基团结合，而不是酶蛋白。

  DOI：

  10.1248/cpb.38.159

文献信息

• Glucuronidation in the chimpanzee (<b><i>Pan troglodytes</i></b>): Studies with acetaminophen, oestradiol and morphine
  作者：H. Wong、H. Wong、J. E. Grace Jr、M. R. Wright、H. Wong、J. E. Grace Jr、M. R. Wright、M. R. Browning、S. J. Grossman、S. A. Bai、H. Wong、J. E. Grace Jr、M. R. Wright、M. R. Browning、S. J. Grossman、S. A. Bai、D. D. Christ、H. Wong、J. E. Grace Jr、M. R. Wright、M. R. Browning、S. J. Grossman、S. A. Bai、D. D. Christ

  DOI：10.1080/00498250600911028

  日期：2006.1

  The chimpanzee has recently been characterized as a surrogate for oxidative drug metabolism in humans and as a pharmacokinetic model for the selection of drug candidates. In the current study, the glucuronidation of acetaminophen, morphine and oestradiol was evaluated in the chimpanzee to extend the characterization of this important animal model. Following oral administration of acetaminophen (600 mg) to chimpanzees (n=2), pharmacokinetics were comparable with previously reported human values, namely mean oral clearance 0.91 vs. 0.62 +/- 0.051h(-1) kg(-1), apparent volume of distribution 2.29 vs. 1.65 +/- 0.25 l kg(-1), and half- life 1.86 vs. 1.89 +/- 0.27 h, for chimpanzee vs. human, respectively. Urinary excretions ( percentage of dose) of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate were also similar between chimpanzees and humans, namely 2.3 vs. 5.0, 63.1 vs. 54.7, and 25.0 vs. 32.3%, respectively. Acetaminophen, oestradiol and morphine glucuronide formation kinetics were investigated using chimpanzee (n=2) and pooled human liver microsomes (n=10). V-max(app) and K-m(app) (or S-50(app)) for acetaminophen glucuronide, morphine 3- and 6-glucuronide, and oestradiol 3- and 17- glucuronide formation were comparable in both species. Eadie-Hofstee plots of oestradiol 3- glucuronide formation in chimpanzee microsomes were characteristic of autoactivation kinetics. Western immunoblot analysis of chimpanzee liver microsomes revealed a single immunoreactive band when probed with anti-human UGT1A1, anti-human UGT1A6, and anti-human UGT2B7. Taken collectively, these data demonstrate similar glucuronidation characteristics in chimpanzees and humans.