56715-13-0

Basic information

• Product Name: (+)-4-[2-HYDROXY-3-[(1-METHYLETHYL)-AMINO]PROPOXY]BENZENEACETAMIDE
• Synonyms: (R)-(+)-ATENOLOL;R(+)-ATENOLOL LESS ACTIVE ENANTIOME;Benzeneacetamide, 4-[(2R)-2-hydroxy-3-[(1-methylethyl)amino]propoxy]-;Benzeneacetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-, (R)-;4-[(R)-2-Hydroxy-3-[(1-methylethyl)amino]propoxy]benzeneacetamide;2-[4-[(2R)-2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetamide;2-[4-[(2R)-2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]acetamide;2-[4-[(2R)-2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]ethanamide
• CAS NO: 56715-13-0
• Molecular Formula: C₁₄H₂₂N₂O₃
• Molecular Weight: 266.34
• Product Categories: Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 56715-13-0.mol
• Article Data: 16

Chemical Properties

• Melting Point: 148-152 °C(lit.)
• Boiling Point: 508°Cat760mmHg
• Flash Point: 261.1°C
• Appearance: pale yellow/solid
• Density: 1.125g/cm³
• Vapor Pressure: 3.82E-11mmHg at 25°C
• Refractive Index: 1.54
• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: >6.0 m
• PKA: 13.88±0.20(Predicted)
• CAS DataBase Reference: (+)-4-[2-HYDROXY-3-[(1-METHYLETHYL)-AMINO]PROPOXY]BENZENEACETAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (+)-4-[2-HYDROXY-3-[(1-METHYLETHYL)-AMINO]PROPOXY]BENZENEACETAMIDE(56715-13-0)
• EPA Substance Registry System: (+)-4-[2-HYDROXY-3-[(1-METHYLETHYL)-AMINO]PROPOXY]BENZENEACETAMIDE(56715-13-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 56715-13-0(Hazardous Substances Data)

Usage

Description

(+)-Atenolol is an enantiomer of the β1-adrenergic receptor (β1-AR) antagonist (±)-atenolol . (+)-Atenolol inhibits radioligand binding to β-ARs on sarcolemma-enriched membranes (Ki = 8.61 μM). Unlike (–)-atenolol and (±)-antenolol, (+)-atenolol has no effect on blood pressure in spontaneously hypertensive rats.

Definition

ChEBI: The (R)-enantiomer of atenolol.

references

[1] stoschitzky k, egginger g, zernig g, et al. stereoselective features of (r)- and (s)-atenolol: clinical pharmacological, pharmacokinetic, and radioligand binding studies[j]. chirality, 1993, 5(1): 15-19.

InChI:InChI=1/C14H22N2O3/c1-10(2)16-8-12(17)9-19-13-5-3-11(4-6-13)7-14(15)18/h3-6,10,12,16-17H,7-9H2,1-2H3,(H2,15,18)/t12-/m1/s1

Upstream product

• 108-05-4 vinyl acetate 
• 29122-68-7 (RS)-atenolol 
• 108-22-5 Isopropenyl acetate 
• 143925-21-7 1--2-acetoxy-3-chloropropane 
• 75-31-0 isopropylamine 
• 115538-83-5 1--3-chloropropan-2-ol 
• 56715-12-9 (S)-2-(4-(3-chloro-2-hydroxypropoxy)phenyl)acetamide 
• 29122-69-8 (S)-1-[p-(carbamoylmethyl)phenoxy]-2,3-epoxypropane 
• 885601-11-6 (2R)-1-isopropylamino-3-[4-(2-acetamido)phenoxy]-2-propanol-(2R,3R)-O,O-di-p-toluoyltartrate 
• 144017-04-9 (S)-1-phenoxy>-2-acetoxy-3-chloropropane 
• 143925-24-0 1-phenoxy>-2-acetoxy-3-chloropropane 
• 144015-98-5 (S)-1-phenoxy>-3-chloropropan-2-ol 
• 143925-23-9 1-phenoxy>-3-chloropropan-2-ol 
• 79419-46-8 4-hydroxyphenylacetic acid butyl este 

Relevant articles and documents

The Reaction Mechanism and Kinetics Data of Racemic Atenolol Kinetic Resolution via Enzymatic Transesterification Process Using Free Pseudomonas fluorescence Lipase

A thorough study on free-enzyme transesterification kinetic resolution of racemic atenolol in a batch system was investigated to gain knowledge for (S)-atenolol kinetics. Analyses of enzyme kinetics using Sigma-Plot 11 Enzyme Kinetics Module on the process are based-on Michaelis-Menten and Lineweaver-Burk plot, which give first-order reaction and ordered-sequential Bi-Bi mechanism, where Vmax, KM-vinyl acetate, and KM-(S)-atenolol are 0.80 mM/h, 29.22 mM, and 25.42 mM, respectively. Further analyses on enzyme inhibitions find that both substrates inhibit the process where (S)-atenolol and vinyl acetate develop competitive inhibition and mixed inhibition, respectively. Association of (S)-atenolol with free enzyme to inhibit the enzyme is higher than reaction of active enzyme-substrate complex with vinyl acetate.

Enantioseparation of (RS)-atenolol with the use of lipases immobilized onto new-synthesized magnetic nanoparticles

The enzymatic method was used for the direct resolution of racemic atenolol. The catalytic activities of commercially available lipases from Candida rugosa (MY and OF) immobilized onto new-synthesized chitosan magnetic nanoparticles [Fe3O4-CS-Et(NH2)2, Fe3O4-CS-Et(NH2)3] in the kinetic resolution of racemic atenolol were compared. The best results were obtained by using Candida rugosa lipase OF immobilized onto Fe3O4-CS-Et(NH2)3. Additionally, the enzyme reusability was investigated. It was established that even after 5 reaction cycles, both lipases from Candida rugosa maintained their high catalytic activities and operational stabilities. This approach is extremely important from an economical point of view, because it allows for a direct cost reduction of the biotransformation.

Enantioseparation of chiral pharmaceuticals by vancomycin-bonded stationary phase and analysis of chiral recognition mechanism

The drug chirality is attracting increasing attention because of different biological activities, metabolic pathways, and toxicities of chiral enantiomers. The chiral separation has been a great challenge. Optimized high-performance liquid chromatography (HPLC) methods based on vancomycin chiral stationary phase (CSP) were developed for the enantioseparation of propranolol, atenolol, metoprolol, venlafaxine, fluoxetine, and amlodipine. The retention and enantioseparation properties of these analytes were investigated in the variety of mobile phase additives, flow rate, and column temperature. As a result, the optimal chromatographic condition was achieved using methanol as a main mobile phase with triethylamine (TEA) and glacial acetic acid (HOAc) added as modifiers in a volume ratio of 0.01% at a flow rate of 0.3?mL/minute and at a column temperature of 5°C. The thermodynamic parameters (eg, ΔH, ΔΔH, and ΔΔS) from linear van 't Hoff plots revealed that the retention of investigated pharmaceuticals on vancomycin CSP was an exothermic process. The nonlinear behavior of lnk′ against 1/T for propranolol, atenolol, and metoprolol suggested the presence of multiple binding mechanisms for these analytes on CSP with variation of temperature. The simulated interaction processes between vancomycin and pharmaceutical enantiomers using molecular docking technique and binding energy calculations indicated that the calculated magnitudes of steady combination energy (ΔG) coincided with experimental elution order for most of these enantiomers.

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase

As the (R)-enantiomer of racemic atenolol has no β-blocking activity and no lack of side effects, switching from the racemate to the (S)-atenolol is more favorable. Transesterification of racemic atenolol using free enzymes investigated as a resource to resolve the racemate via this method is limited. Screenings of enzyme, medium, and acetyl donor were conducted first to give Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical design of the experiment was then developed using Central Composite Design on some operational factors, which resulted in the conversions of 11.70–61.91% and substrate enantiomeric excess (ee) of 7.31–100%. The quadratic models are acceptable with R2 of 95.13% (conversion) and 89.63% (ee). The predicted values match the observed values reasonably well. Temperature, agitation speed, and substrate molar ratio factor have low effects on conversion and ee, but enzyme loading affects the responses highly. The interaction of temperature–agitation speed and temperature–substrate molar ratio show significant effects on conversion, while temperature–agitation speed, temperature–substrate molar ratio, and agitation speed–substrate molar ratio affect ee highly. Optimum conditions for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate were found at 45°C, 175?rpm, 2000?U, and 1:3.6 substrate molar ratio.