5051-22-9

Basic information

• Product Name: R(+)-PROPRANOLOL HCL
• Synonyms: (+)-2-propano;(+)-propranolol;(r)-2-propano;2r-propranolol;d-(+)-propranolol;dexpropranolol;dextropropranolol;d-propranolol
• CAS NO: 5051-22-9
• Molecular Formula: C₁₆H₂₁NO₂
• Molecular Weight: 295.80438
• EINECS: 225-749-2
• Product Categories: Adrenoceptor
• Mol File: 5051-22-9.mol
• Article Data: 50

Chemical Properties

• Melting Point: 96 °C
• Boiling Point: 434.9 °C at 760 mmHg
• Flash Point: 216.8 °C
• Appearance: /
• Density: 1.093 g/cm³
• Vapor Pressure: 2.48E-08mmHg at 25°C
• Refractive Index: 1.58
• Storage Temp.: Store at RT
• PKA: pKa 9.53±0.01(H2O,t=25±0.5,I=0.15(KCl))(Approximate)
• CAS DataBase Reference: R(+)-PROPRANOLOL HCL(CAS DataBase Reference)
• NIST Chemistry Reference: R(+)-PROPRANOLOL HCL(5051-22-9)
• EPA Substance Registry System: R(+)-PROPRANOLOL HCL(5051-22-9)

Safety Data

• Hazardous Substances Data: 5051-22-9(Hazardous Substances Data)

Usage

Description

R(+)-PROPRANOLOL HCL, also known as Inderal, is a prototypical and nonselective β-blocker. It blocks both β1and β2-receptors with equal affinity, lacks intrinsic sympathomimetic activity (ISA), and does not block β-receptors. As a competitive blocker, its receptor-blocking actions can be reversed with sufficient concentrations of β-agonists.

Uses

Used in Cardiology:
R(+)-PROPRANOLOL HCL is used as an anti-arrhythmic agent for conditions such as ventricular tachycardia, arrhythmia caused by digitalis drug overdose, or as a result of thyrotoxosis or excess catecholamine activity. It is considered the first choice of drugs for these conditions, although other β-adrenoblockers and calcium blockers can be just as effective.
Used in Hypertension Treatment:
R(+)-PROPRANOLOL HCL is used as an antihypertensive agent for treating hypertension, angina pectoris, supraventricular arrhythmia, and migraines. It is also used following a myocardial infarction to help manage the postanginal phase and prevent further complications.
Used in Other Medical Applications:
R(+)-PROPRANOLOL HCL is used as a therapeutic agent for various conditions, including hypertrophic subaortic stenosis, pheochromocytosis, and extrasystole. Its versatile application in different medical fields highlights its importance in modern medicine.

Indications

Propranolol slows heart rate, increases the effective refractory period of atrioventricular ganglia, suppresses automatism of heart cells, and reduces excitability and contractibility of the myocardium. It is used for supraventricular and ventricular arrhythmias.

Synthesis Reference(s)

Tetrahedron Letters, 31, p. 2157, 1990 DOI: 10.1016/0040-4039(90)80097-6

Biological Activity

Less active enantiomer of the β -adrenoceptor antagonist propranolol ((RS)-1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol hydrochloride ).

Mechanism of action

Propranolol is a nonselective β-adrenoblocker that affects both the mechanical and electrophysiological properties of the myocardium. It lowers myocardial contractibility, heart rate, blood pressure, and the myocardial need for oxygen. These properties make propranolol and other β-adrenoblockers useful antianginal drugs.

Clinical Use

Currently, R(+)-PROPRANOLOL HCL is approved for use inthe United States for hypertension, cardiac arrhythmias,angina pectoris, postmyocardial infarction, hypertrophiccardiomyopathy, pheochromocytoma, migraine prophylaxis,and essential tremor. In addition, because of its highlipophilicity (log P=3.10) and thus its ability to penetratethe CNS, propranolol has found use in treating anxiety andis under investigation for the treatment of a variety of otherconditions, including schizophrenia, alcohol withdrawalsyndrome, and aggressive behavior.

Side effects

The toxicity associated with propranolol is for the most part related to its primary pharmacological action, inhibition of the cardiac β-adrenoceptors. In addition, propranolol exerts direct cardiac depressant effects that become manifest when the drug is administered rapidly by the IV route.Glucagon immediately reverses all cardiac depressant effects of propranolol, and its use is associated with a minimum of side effects. The inotropic agents amrinone (Inocor) and milrinone (Primacor) provide alternative means of augmenting cardiac contractile function in the presence of β-adrenoceptor blockade. Propranolol may also stimulate bronchospasm in patients with asthma. Since propranolol crosses the placenta and enters the fetal circulation, fetal cardiac responses to the stresses of labor and delivery will be blocked. Additionally, propranolol crosses the blood-brain barrier and is associated with mood changes and depression. School difficulties are commonly associated with its use in children. Propranolol may also cause hypoglycemia in infants.

Synthesis

Propranolol, 1-(iso-propylamino)-3-(1-naphthyloxy)-2-propanol (12.1.2), is synthesized in two ways from the same initial substance. The first way consists of reacting 1-naphthol with epichlorohydrin. Opening of the epoxide ring gives 1-chloro-3- (1-naphthyloxy)-2-propanol (12.1.1), which is reacted further with iso-propylamine, giving propranolol (12.1.2). The second method uses the same reagents in the presence of a base and consists of initially making 3-(1-naphthyloxy)propylenoxide (12.1.3), the subsequent reaction with isopropylamine which results in epoxide ring opening leading to the formation of propranolol (12.1.2) [1–6].

Metabolism

Propranolol (Inderal) is suitable for both parental and oral administration. Absorption from the gastrointestinal tract is extensive. The peak therapeutic effect after oral administration occurs in 1 to 1.5 hours.The plasma half-life of propranolol is approximately 3 hours. The drug is concentrated in the lungs and to a lesser extent in the liver, brain, kidneys, and heart. Binding to plasma proteins is extensive (90%). The liver is the chief organ involved in the metabolism of propranolol, and the drug is subject to a significant degree of first-pass metabolism. At least eight metabolites have been recovered from the urine, the major excretory route.

Precautions

Propranolol is contraindicated for patients with depressed myocardial function and may be contraindicated in the presence of digitalis toxicity because of the possibility of producing complete A-V block and ventricular asystole. Patients receiving anesthetic agents that tend to depress myocardial contractility (ether, halothane) should not receive propranolol. Propranolol should be used with extreme caution in patients with asthma. Up-regulation of β-receptors follows long-term therapy, making abrupt withdrawal of β-blockers dangerous for patients with ischemic heart disease.

InChI:InChI=1/C16H21NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h3-9,12,14,17-18H,10-11H2,1-2H3/t14-/m1/s1

Upstream product

• 525-66-6 propranolol 
• 90-15-3 α-naphthol 
• 61248-78-0 (R)-3-(1-naphthyloxy)-1,2-propanediol 
• 75-31-0 isopropylamine 
• 129520-27-0 (R)-propranolol O-acetyl ester 
• 20133-93-1 1-chloro-3-(1-naphthoxy)-2-propanol 
• 183428-30-0 1-{[1-Naphthalen-1-yl-meth-(Z)-ylidene]-amino}-3-(naphthalen-1-yloxy)-propan-2-ol 
• 20862-11-7 (S)-1-Amino-3-(naphthalen-1-yloxy)-propan-2-ol 
• 67-64-1 acetone 
• 589-96-8 (+/-)-1-Acetoxy-2,3-dichloropropane 
• 149874-40-8 (R)-N-butyryl propranolol 
• 103470-56-0 N-[2-Hydroxy-3-(naphthalen-1-yloxy)-propyl]-2-phenyl-acetamide 
• 88547-39-1 (+)-Desisopropylpropranolol 
• 81102-69-4 Toluene-4-sulfonic acid (S)-2-hydroxy-3-(naphthalen-1-yloxy)-propyl ester 

Relevant articles and documents

Preparation of a novel hydroxypropyl-γ-cyclodextrin functionalized monolith for separation of chiral drugs in capillary electrochromatography

In this study, a novel hydroxypropyl-γ-cyclodextrin (HP-γ-CD) functionalized monolithic capillary column was prepared by one-pot sequential strategy and used for chiral separation in capillary electrochromatography for the first time. In one pot, GMA-HP-γ-CD as functional monomer was allowed to be formed via the ring opening reaction between HP-γ-CD and glycidyl methacrylate (GMA) catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and then copolymerized directly with ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) in the presence of porogenic solvents via thermally initiated free radical polymerization. The preparation conditions of monoliths were optimized. Enantiomer separations of six chiral drugs including pindolol, clorprenaline, tulobuterol, clenbuterol, propranolol, and tropicamide were achieved on the monolith. Among them, pindolol, clorprenaline, and tropicamide were baseline separated with resolution values of 1.62, 1.73, and 1.55, respectively. The mechanism of enantiomer separation was discussed by comparison of the HP-γ-CD and HP-β-CD functionalized monoliths.

Enantioseparation of mandelic acid on vancomycin column: Experimental and docking study

So far, no detailed view has been expressed regarding the interactions between vancomycin and racemic compounds including mandelic acid. In the current study, a chiral stationary phase was prepared by using 3-aminopropyltriethoxysilane and succinic anhydride to graft carboxylated silica microspheres and subsequently by activating the carboxylic acid group for vancomycin immobilization. Characterization by elemental analysis, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, and thermogravimetric analysis demonstrated effective functionalization of the silica surface. R and S enantiomers of mandelic acid were separated by the synthetic vancomycin column. Finally, the interaction between vancomycin and R/S mandelic acid enantiomers was simulated by Auto-dock Vina. The binding energies of interactions between R and S enantiomers and vancomycin chiral stationary phase were different. In the most probable interaction, the difference in mandelic acid binding energy was approximately 0.2 kcal/mol. In addition, circular dichroism spectra of vancomycin interacting with R and S enantiomers showed different patterns. Therefore, R and S mandelic acid enantiomers may occupy various binding pockets and interact with different vancomycin functions. These observations emphasized the different retention of R and S mandelic acid enantiomers in vancomycin chiral column.

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.