托特罗定杂质 | 131564-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 托特罗定杂质
• 英文名称: (+)-O-Demethylmetoprolol
• 英文别名: 4-((2R)-2-Hydroxy-3-((1-methylethyl)amino)propoxy)benzeneethanol；(2R)-1-[4-(2-hydroxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
• CAS: 131564-70-0
• 化学式: C₁₄H₂₃NO₃
• 分子量: 253.342
• InChiKey: CUKXSBOAIJILRY-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  61.7
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

O-去甲基美托洛尔是已知的人体内(r)-美托洛尔的代谢物。

O-Demethylmetoprolol is a known human metabolite of (r)-metoprolol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  美托洛尔 在 potassium phosphate buffer 、 microsomal protein h2D₆v2 、 NADPH-generating system 作用下， 反应 0.5h， 生成 托特罗定杂质
  参考文献：
  名称：

  摘要：

  Purpose. The oxidative metabolism of metoprolol was investigated in two human lymphoblastoma cell-lines transfected with variants of cDNA for cytochrome P4502D6.Methods. The regioselective and enantioselective features of the oxidations of deuterium-labeled pseudoracemic metoprolol were characterized by GC/MS analysis of the substrate and products.Results. There were significant differences between the two P4502D6 variants in the formation kinetics of O-demethylnetoprolol and alpha-hydroxymetoprolol. The h2D6-Val microsomes highly favored the formation of the O-demethylmetoprotol regioisomer 6.3:1 and 2.8:1, respectively from (R)-metoprolol-d(0) and (S)-metoprolol-d(2), while the corresponding ratios for h2D6v2 microsomes were much lower. For both variants, O-demethylmetoprolol formation favored the (R)-substrate 1.5 to 2-fold, while alpha-hydroxymetoprolol formation was non-enantioselective. Similar Km values of metoprolol oxidation, 10-20 mu M, were observed for the two microsomal preparations.Conclusions. The regioselectivity, enantioselectivity, and Km values for the h2D6-Val microsomes resemble those observed for the native P4502D6 in human liver microsomes, whereas the h2D6v2 microsomes deviated remarkably in regioselectivity.

  DOI：

  10.1023/a:1016233115443

文献信息

• ——
  作者：Douglas S. Mautz、Danny D. Shen、Wendel L. Nelson

  DOI：10.1023/a:1016233115443

  日期：——

  Purpose. The oxidative metabolism of metoprolol was investigated in two human lymphoblastoma cell-lines transfected with variants of cDNA for cytochrome P4502D6.Methods. The regioselective and enantioselective features of the oxidations of deuterium-labeled pseudoracemic metoprolol were characterized by GC/MS analysis of the substrate and products.Results. There were significant differences between the two P4502D6 variants in the formation kinetics of O-demethylnetoprolol and alpha-hydroxymetoprolol. The h2D6-Val microsomes highly favored the formation of the O-demethylmetoprotol regioisomer 6.3:1 and 2.8:1, respectively from (R)-metoprolol-d(0) and (S)-metoprolol-d(2), while the corresponding ratios for h2D6v2 microsomes were much lower. For both variants, O-demethylmetoprolol formation favored the (R)-substrate 1.5 to 2-fold, while alpha-hydroxymetoprolol formation was non-enantioselective. Similar Km values of metoprolol oxidation, 10-20 mu M, were observed for the two microsomal preparations.Conclusions. The regioselectivity, enantioselectivity, and Km values for the h2D6-Val microsomes resemble those observed for the native P4502D6 in human liver microsomes, whereas the h2D6v2 microsomes deviated remarkably in regioselectivity.