Sotalol Chemical Properties

Melting point:

206.5-207 °C

Boiling point:

443.3±55.0 °C(Predicted)

Density 

1.298 g/cm3

storage temp. 

Hygroscopic, -20°C Freezer, Under inert atmosphere

solubility 

Chloroform (Slightly, Heated), Methanol (Slightly, Sonicated)

pka

pK1 8.2, pK2 9.8(at 25℃)

form 

Solid

color 

Pale Yellow to Light Yellow

BCS Class

1

Stability:

Hygroscopic

InChI

InChI=1S/C12H20N2O3S/c1-9(2)13-8-12(15)10-4-6-11(7-5-10)14-18(3,16)17/h4-7,9,12-15H,8H2,1-3H3

InChIKey

ZBMZVLHSJCTVON-UHFFFAOYSA-N

SMILES

CS(NC1=CC=C(C(O)CNC(C)C)C=C1)(=O)=O

CAS DataBase Reference

3930-20-9(CAS DataBase Reference)

NIST Chemistry Reference

Methanesulfonanilide, 4'-(1-hydroxy-2-(isopropylamino)ethyl)-(3930-20-9)

EPA Substance Registry System

Methanesulfonamide, N-[4-[1-hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]- (3930-20-9)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

Sotalol Usage And Synthesis

Originator

Sotagard,Glaxo

Definition

ChEBI: A sulfonamide that is N-phenylmethanesulfonamide in which the phenyl group is sustituted at position 4 by a 1-hydroxy-2-(isopropylamino)ethyl group. It has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and ardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. It is used (usually as the hydrochloride salt) for the management of ventricular and supraventricular arrhythmias.

Manufacturing Process

As a resulting of reaction of methansulfonylchloride reacted with aniline methansulfonanilide was obtained. The methansulfonanilide reacted with bromacetylbromide at the presence of AlCl3 and CS2 and 4-(bromacetyl)- methansulfonanilide was prepeared.
Then to the 4-(bromacetyl)-methansulfonanilide isopropylamine was added to give 4-(1-oxo-2-isopropylaminoethyl)methansulfonanilide.The 4-(1-oxo-2-isopropylaminoethyl)methansulfonanilide was reduced by hydrogenesation in the presence of Pd-C catalyst and sodium borohydride. So 4-(1-hydroxy-2-isopropylaminoethyl)methansulfonanilide was obtained.
The 4-(1-hydroxy-2-isopropylaminoethyl)methansulfonanilide hydrochloride may be prepared by treatment of base with hydrochloric acid.

Therapeutic Function

Beta-adrenergic blocker, Antiarrhythmic

World Health Organization (WHO)

Sotalol is a non-selective?-adrenoreceptor antagonist. It should be noted that when stopping sotalol the dose should be reduced gradually.

General Description

Sotalol, 4＇[1-hydroxy-2-(isopropylamino)ethyl]methylsulfonanilide (Betapace), is a relatively new antiarrhythmicdrug, characterized most often as a class IIIagent, and although it has effects that are related to the classII agents, it is not therapeutically considered a class II antiarrhythmic.It contains a chiral center and is marketed as theracemic mixture. Because of its enantiomers, its mechanismof action spans two of the antiarrhythmic drug classes. Thel(-) enantiomer has both β-blocking (class II) and potassiumchannel-blocking (class III) activities. The d(+) enantiomerhas class III properties similar to those of the (-) isomer,but its affinity for the -adrenergic receptor is 30 to 60 timeslower.

Biological Activity

sotalol hydrochloride is an adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias.

Mechanism of action

Sotalol acts as an antiarrhythmic by β- receptor blockade as well as by prolonging the action potential duration in atrium and ventricle and the refractory period in atrium and AV node . Activity against supraventricular and ventricular arrhythmiaswas demonstrated.

Clinical Use

The sotalol enantiomers produce different effects onthe heart. Class III action of d-sotalol in the sinus node isassociated with slowing of sinus heart rate, whereas -adrenergicblockade contributes to the decrease in heart rate observedwith 1- or d,1-sotalol. Sotalol is not metabolized, noris it bound significantly to proteins. Elimination occurs byrenal excretion, with more than 80% of the drug eliminatedunchanged. Sotalol is characteristic of class III antiarrhythmicdrugs, in that it prolongs the duration of the action potentialand, thus, increases the effective refractory period of myocardialtissue. It is distinguished from the other class III drugs(amiodarone and bretylium) because of its -adrenergicreceptor–blocking action.

Side effects

Side effects of sotalol include those attributed to both β-adrenoceptor blockade and proarrhythmic effects. This arrhythmia is a serious threat, as it may lead to ventricular fibrillation. Adverse effects attributable to its β- blocker activity include fatigue, dyspnea, chest pain, headache, nausea, and vomiting.

Drug interactions

Drugs with inherent QT interval–prolonging activity (i.e., thiazide diuretics and terfenadine) may enhance the class III effects of sotalol.

Precautions

The contraindications that apply to other β-adrenoceptor blocking agents also apply to sotalol. In addition, hypokalemia and drugs known to prolong the QT interval may be contraindicated, as they enhance the possibility of proarrhythmic events.

Sotalol(3930-20-9)Related Product Information

• Ethylparaben
• 2-Ethylaniline
• 3-Diethylaminophenol
• 4-Hydroxyaniline hydrochloride
• Isopropylamine
• Phenylhydrazine
• CHLOROPHOSPHONAZO III
• Ethanesulfonyl chloride
• Ethyl acrylate
• Diisopropylammonium dichloroacetate
• PHENYL VALERATE
• p-(2-Methoxyethyl) phenol
• Diisopropylamine
• Ethanol
• Ethyl acetate
• [2H6]-Sotalol
• (S)-Sotalol
• D,L-Sotalol, Hydrochloride,SOTALOL HYDROCHLORIDE,SOTALOL HCL,(+/-)-SOTALOL HYDROCHLORIDE,SOTALOL HYDROCHLORIDE BP