62572-94-5

Usage

Uses

Used in Pharmaceutical Industry:
O-Desmethyl Metoprolol is used as an active metabolite for enhancing the therapeutic effects of Metoprolol. As a metabolite, it contributes to the overall pharmacological action of Metoprolol, which is primarily used to treat conditions such as hypertension, angina, and certain types of arrhythmias. The presence of O-Desmethyl Metoprolol can influence the drug's efficacy and duration of action, making it an important consideration in the development and optimization of Metoprolol-based treatments.
Additionally, O-Desmethyl Metoprolol may be used as a reference compound or impurity standard in the quality control and regulatory processes of Metoprolol drug formulations, ensuring the safety and efficacy of the medication.

InChI:InChI=1/C14H23NO3/c1-11(2)15-9-13(17)10-18-14-5-3-12(4-6-14)7-8-16/h3-6,11,13,15-17H,7-10H2,1-2H3

Upstream product

• 51384-51-1 (RS)-metoprolol 
• 104857-48-9 1-[4-(2-hydroxyethyl)phenoxy]-2,3-epoxypropane 
• 297741-05-0 (S)-1-[4-(2-hydroxyethyl)phenoxy]-2,3-epoxypropane 
• 501-94-0 p-hydroxyphenethyl alcohol 
• 1312687-84-5 C₁₈H₂₇NO₅ 
• 959279-50-6 C₂₀H₂₉NO₆ 
• 29122-68-7 (RS)-atenolol 
• 75-31-0 isopropylamine 
• 81024-43-3 (2R)-metoprolol 

Downstream Products

• 1237781-36-0 C₁₆H₂₅NO₄ 
• 1312687-84-5 C₁₈H₂₇NO₅ 
• 947340-61-6 (5S)-2-(4-((3-isopropyl-2-phenyloxazolidin)-5-methoxy)phenyl)-4-ethanol 
• 104857-50-3 (5S)-5-(4-((2-cyclopropylmethoxy)ethyl)phenoxy)methyl-3-isopropyl-2-phenyloxazolidine 

Relevant academic research and scientific papers

Regioselectivity and enantioselectivity of metoprolol oxidation by two variants of cDNA-expressed P4502D6

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-demethylmetoprolol and α-hydroxymetoprolol. The h2D6-Val microsomes highly favored the formation of the O-demethylmetoprolol regioisomer 6.3:1 and 2.8:1, respectively from (R)-metoprolol-d0 and (S)-metoprolol-d2, 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 α-hydroxymetoprolol formation was non-enantioselective. Similar Km values of metoprolol oxidation, 10-20 μM, 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.

Preparation method and application of 1-[(4-hydroxyethyl) phenoxy]-3-(isopropylamino) propan-2-ol

The invention belongs to the technical field of medicine preparation, and mainly relates to a preparation method of a compound 1-[(4-hydroxyethyl) phenoxy]-3-(isopropylamino) propyl-2-ol and application of the compound in betalol hydrochloride and betalol

Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes

The use of medicinal plants concomitantly with conventional drugs can result in herb-drug interactions that cause fluctuations in drug bioavailability and consequent therapeutic failure and/or toxic effects. The CYP superfamily of enzymes plays an importa

Technique for synthesizing levorotatory betaxolol hydrochloride (by machine translation)

The invention discloses a technique for synthesizing levorotatory betaxolol hydrochloride, the process adopts to hydroxy phenylacetic alcohol and R- epoxy halogen propane is used as starting material, under certain conditions after alkylation, amination,

Highly chemoselective reduction of amides (primary, secondary, tertiary) to alcohols using SmI2/amine/H2O under mild conditions

Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C-N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C-O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the nX → πC=O (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C-N/C-O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions.

Chemoenzymatic route to S-betaxolol

An efficient chemoenzymatic route to S-betaxolol is reported. A strain (Rhodotorula mucilaginosa DQ832198) screened from soil was used as biocatalyst for the kinetic resolution of the key acetylated intermediates. Excellent enantiomeric excess (ee99%) was

Preparation of human drug metabolites using fungal peroxygenases

The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites (HDMs) via selective monooxygenation remains a challenging task for synthetic organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1) secreted by the agaric fungi Agrocybe aegerita and Coprinellus radians catalyzed the H2O2-dependent selective monooxygenation of diverse drugs, including acetanilide, dextrorphan, ibuprofen, naproxen, phenacetin, sildenafil and tolbutamide. Reactions included the hydroxylation of aromatic rings and aliphatic side chains, as well as O- and N-dealkylations and exhibited different regioselectivities depending on the particular APO used. At best, desired HDMs were obtained in yields greater than 80% and with isomeric purities up to 99%. Oxidations of tolbutamide, acetanilide and carbamazepine in the presence of H218O2 resulted in almost complete incorporation of 18O into the corresponding products, thus establishing that these reactions are peroxygenations. The deethylation of phenacetin-d1 showed an observed intramolecular deuterium isotope effect [(kH/kD) obs] of 3.1 ± 0.2, which is consistent with the existence of a cytochrome P450-like intermediate in the reaction cycle of APOs. Our results indicate that fungal peroxygenases may be useful biocatalytic tools to prepare pharmacologically relevant drug metabolites.

Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data

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 P450 (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 P450 (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 (r2=0.50) but significant (Pint 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 (int 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.

The molecular and enzyme kinetic basis for the diminished activity of the cytochrome P450 2D6.17 (CYP2D6.17) variant: Potential implications for CYP2D6 phenotyping studies and the clinical use of CYP2D6 substrate drugs in some African populations

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 Km values compared to CYP2D6.1. The Vmax values were generally not different except for metoprolol α-hydroxylation with the Vmax value for CYP2D6.17 being half that of CYP2D6.1. 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.

Process for preparing substituted phenol ethers via oxazolidine-structure intermediates

Phenol ethers such as 1-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol, otherwise known as betaxolol, of formula: STR1 are prepared from p-hydroxyphenethyl alcohol by first reacting at the phenolic group, with epichlorohydrin followed by isopropylamine, to prepare the required secondary amine-hydroxy side chain. Protection of the alcoholic group is not required during these steps. Then the secondary amine-alcohol group is protected by reaction with a suitable aldehyde such as benzaldehyde to form an oxazolidine ring protectant while the alcohol chain is elaborated. The oxazolidine ring protectant is removed by simple acid hydrolysis.