A-羟基美托洛尔 | 56392-16-6

• 物质功能分类: 分析化学 - 分析试剂 - 离子色谱试剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: A-羟基美托洛尔
• 中文别名: Alpha-羟基美托洛尔；Α-羟基美托洛尔
• 英文名称: alpha-Hydroxymetoprolol
• 英文别名: α-hydroxymetoprolol；1-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
• CAS: 56392-16-6
• 化学式: C₁₅H₂₅NO₄
• mdl: MFCD00871829
• 分子量: 283.368
• InChiKey: OFRYBPCSEMMZHR-UHFFFAOYSA-N

物化性质

• 熔点：
  65-67°C
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

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

安全信息

• WGK Germany：
  3
• 储存条件：
  -20°C冷冻库

制备方法与用途

a-羟基美托洛尔是美托洛尔的代谢产物，其对美托洛尔的肾上腺素受体阻断作用几乎可以忽略不计。

反应信息

• 作为反应物：
  描述：

  A-羟基美托洛尔 生成 美托洛尔
  参考文献：
  名称：

  HUHTA, S. K.;KOSKENNISKA, L. A.

  摘要：

  DOI：
• 作为产物：
  描述：

  美托洛尔 在 unspecific monooxygenase 还原型辅酶II(NADPH)四钠盐 作用下， 以 phosphate buffer 为溶剂， 生成 A-羟基美托洛尔
  参考文献：
  名称：

  Identification of human cytochrome P 450 s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data

  摘要：

  Objective. Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P-450 (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vivo drug clearances from in vitro data.Methods. In vitro systems, rat and human liver microsomes (RLM, HLM) and recombinant cytochrome P-450 (rCYP), were used to determine the intrinsic clearance (CLint) and identify responsible CYPs and their relative contribution in the metabolism of 15 commonly used APDs.Results and discussion. CLint determined in RLM and HLM showed low (r(2)=0.50) but significant (P<0.01) correlation. The CLint values were scaled to predict in vivo hepatic clearance (CLH) using the 'venous equilibrium model'. The number of compounds with in vivo human CL data after intravenous administration was low (n=8), and the range of CL values covered by these compounds was not appropriate for a reasonable quantitative in vitro-in vivo correlation analysis. Using the CLH predicted from the in vitro data, the compounds could be classified into three different categories: high-clearance drugs (>70% liver blood flow; amodiaquine, praziquantel, albendazole, thiabendazole), low-clearance drugs (<30% liver blood flow; chloroquine, dapsone, diethylcarbamazine, pentamidine, primaquine, pyrantel, pyrimethamine, tinidazole) and intermediate clearance drugs (artemisinin, artesunate, quinine). With the exception of artemisinin, which is a high clearance drug in vivo, all other compounds were classified using in vitro data in agreement with in vivo observations. We identified hepatic CYP enzymes responsible for metabolism of some compounds (praziquantel-1A2, 2C19, 3A4; primaquine-1A2, 3A4; chloroquine-2C8, 2D6, 3A4; artesunate-2A6; pyrantel-2D6). For the other compounds, we confirmed the role of previously reported CYPs for their metabolism and identified other CYPs involved which had not been reported before.Conclusion. Our results show that it is possible to make in vitro-in vivo predictions of high, intermediate and low CLint drug categories. The identified CYPs for some of the drugs provide a basis for how these drugs are expected to behave pharmacokinetically and help in predicting drug-drug interactions in vivo.

  DOI：

  10.1007/s00228-003-0636-9

文献信息

• Chemical aspects of metoprolol metabolism. Asymmetric synthesis and absolute configuration of the 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1-(isopropylamino)-2-propanols, the diastereomeric benzylic hydroxylation metabolites
  作者：H. Umesha Shetty、Wendel L. Nelson

  DOI：10.1021/jm00396a009

  日期：1988.1

  for the diastereomers. The absolute configurations 1'S,2S and 1'S,2R were assigned for the diastereomers formed in excess on the basis of reductions on closely related alkyl phenyl ketones and the circular dichroism spectrum. Derivatization of the 1'-hydroxyl group of oxazolidinone 10 with a chiral Mosher acid chloride and the use of an HPLC procedure to resolve the resulting esters enabled us to determine

  描述了美托洛尔（1）的苄基羟化代谢产物3- [4-（1-羟基-2-甲氧基乙基）苯氧基] -1-（异丙氨基）-2-丙醇（2）的不对称合成，并描述了其绝对构型分配了非对映异构体。用（2S）-（-）-2-氨基-3-甲基-1,1-二苯基丁烷-1-醇（9）和硼烷的络合物将多步合成制得的酮3还原为2，非对映异构体的比例为82:18。过量构型的非对映异构体的绝对构型1'S，2S和1'S，2R基于紧密相关的烷基苯基酮的还原和圆二色性光谱而指定。1'的衍生化
• Transformation of metoprolol in UV/PDS process: Role and mechanisms of degradation and polymerization
  作者：Sui-Qin Yang、Rui-Qiu Ye、Yu-Hong Cui、Zheng-Qian Liu、Kai Sun、Yu-Ze Yu

  DOI：10.1016/j.jhazmat.2024.134498

  日期：2024.7

  Advanced oxidation processes for the treatment of organic pollutants in wastewater suffer from difficulties in mineralization, potential risks of dissolved residues, and high oxidant consumption. In this study, radical-initiated polymerization is dominated in an UV/peroxydisulfate (PDS) process to eliminate organic pollutant of pharmaceutical metoprolol (MTP). Compared with an ideal degradation-based

  高级氧化工艺处理废水中的有机污染物存在矿化困难、溶解残渣潜在风险和氧化剂消耗高等问题。在这项研究中，自由基引发聚合在紫外/过二硫酸盐（PDS）工艺中占主导地位，以消除药物美托洛尔（MTP）的有机污染物。与理想的基于降解的UV/PDS工艺相比，本工艺可以节省五分之四的PDS消耗，同时去除47.3%的溶解有机碳。同时，通过以初始化学需氧量50%的比例分离固体聚合物，可以从水溶液中回收有机碳。分析产物的化学结构以推断MTP的转化途径。与以往对简单有机污染物的研究中聚合可以独立发生不同，MTP的聚合依赖于MTP的部分降解，聚合中的主要单体是主要的降解产物（4-(2-甲氧基乙基)-苯酚，记为如 DP151）。分离出的固体聚合物是通过一系列中间低聚物对DP151或其衍生物进行重复氧化和偶联而形成的。这项概念验证研究证明了以聚合为主导的机制在处理具有复杂结构的大有机分子方面的优势，以及 UV/PDS 工
• The molecular and enzyme kinetic basis for the diminished activity of the cytochrome P450 2D6.17 (CYP2D6.17) variant
  作者：Tashinga E Bapiro、Julia A Hasler、Marianne Ridderström、Collen M Masimirembwa

  DOI：10.1016/s0006-2952(02)01351-5

  日期：2002.11

  In this study, the basis for the diminished capacity of CYP2D6.17 to metabolise CYP2D6 substrate drugs and the possible implications this might have for CYP2D6 phenotyping studies and clinical use of substrate drugs were investigated in vitro. Enzyme kinetic analyses were performed with recombinant CYP2D6.1, CYP2D6.2, CYP2D6.17 and CYP2D6.T107I using bufuralol, debrisoquine, metoprolol and dextromethorphan as substrates. In addition, the intrinsic clearance of 10 CYP2D6 substrate drugs by CYP2D6.1 and CYP2D6.17 was determined by monitoring substrate disappearance. CYP2D6.17 exhibited generally higher K-m values compared to CYP2136.1. The V-max values were generally not different except for metoprolol alpha-hydroxylation with the V-max value for CYP2D6.17 being half that of CYP2D6. L CYP2D6.1 and CYP2D6.2 displayed similar kinetics with all probe drugs except for dextromethorphan O-demethylation with the intrinsic clearance value of CYP2D6.2 being half that of CYP2D6.1. CYP2D6.17 exhibited substrate-dependent reduced clearances for the 10 substrates studied. In a clinical setting, the clearance of some drugs could be affected more than others in individuals with the CYP2D6*17 variant. The CYP2D6*17 allele might, therefore, contribute towards the poor correlation of phenotyping results when using different probe drugs in African populations. To investigate effects of CYP2D6*17 mutations on the structure of the enzyme, a homology model of CYP2D6 was built using the CYP2C5 crystal structure as a template. The results suggest an alteration in position of active-site residues in CYP2D6.17 as a possible explanation for the reduced activity of the enzyme. (C) 2002 Elsevier Science Inc. All rights reserved.
• SHETTY, H. UMESHA;NELSON, WENDEL L., J. MED. CHEM., 31,(1988) N 1, 55-59
  作者：SHETTY, H. UMESHA、NELSON, WENDEL L.

  DOI：——

  日期：——
• GYLLENHAAL O.; VESSMAN J., J. CHROMATOGR., 395,(1987) 445-453
  作者：GYLLENHAAL O.、 VESSMAN J.

  DOI：——

  日期：——