(2R)-1-[4-(1-羟基-2-甲氧基乙基)苯氧基]-3-(丙-2-基氨基)丙-2-醇 | 110458-46-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: (2R)-1-[4-(1-羟基-2-甲氧基乙基)苯氧基]-3-(丙-2-基氨基)丙-2-醇
• 英文名称: (2R)-α-hydroxymetoprolol
• 英文别名: 3-(4-(1-Hydroxy-2-methoxyethyl)phenoxy)-1-(isopropylamino)-2-propanol；(2R)-1-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
• CAS: 110458-46-3
• 化学式: C₁₅H₂₅NO₄
• 分子量: 283.368
• InChiKey: OFRYBPCSEMMZHR-AFYYWNPRSA-N

物化性质

• 沸点：
  437.6±45.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  71
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

阿尔法-羟基美托洛尔是已知的人体代谢物，来源于（R）-美托洛尔。

Alpha-Hydroxymetoprolol 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 (2R)-1-[4-(1-羟基-2-甲氧基乙基)苯氧基]-3-(丙-2-基氨基)丙-2-醇
  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.