N-(4-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}phenyl)methanesulfonamide

• ChemBase ID: 372
• Molecular Formular: C12H20N2O3S
• Molecular Mass: 272.3638
• Monoisotopic Mass: 272.11946351
• SMILES: S(=O)(=O)(Nc1ccc(C(O)CNC(C)C)cc1)C
• Canonical SMILES: CC(NCC(c1ccc(cc1)NS(=O)(=O)C)O)C
• 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

NAMES AND DATABASE IDS

Names

• IUPAC name: N-(4-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}phenyl)methanesulfonamide
• IUPAC Traditional name: sotalol
• Brand Name: Betapace; Betapace AF; Sorine
• Synonyms: Sotalol HCL; Sotalol; N-[4-[1-Hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]methanesulfonamide Hydrochloride; 4'-[1-Hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide Hydrochloride; Betapace; DL-MJ 1999; Darob; MJ 1999; Sotacor; Sotalex; dl-Sotalol Hydrochloride; Sotalol Hydrochloride

Database IDs

• CAS Number: 3930-20-9; 959-24-0
• PubChem SID: 160963835; 46505012
• PubChem CID: 5253
• ATC CODE: C07AA07
• CHEMBL: 471
• Chemspider ID: 5063
• DrugBank ID: DB00489
• KEGG ID: D08525
• Unique Ingredient Identifier: A6D97U294I
• Wikipedia Title: Sotalol
• Medline Plus: a693010

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.069403
• H Acceptors: 4
• H Donor: 3
• LogD (pH = 5.5): -3.138338
• LogD (pH = 7.4): -2.1217964
• Log P: -0.395064
• Molar Refractivity: 71.1191 cm^3
• Polarizability: 28.832848 Å^3
• Polar Surface Area: 78.43 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.85
• LOG S: -2.54
• Solubility (Water): 7.82e-01 g/l

PROPERTIES

Physical Property

• Solubility: Soluble (5510 mg/L); Water
• Apperance: White Crystalline Solid
• Melting Point: 218-220°C
• Hydrophobicity(logP): 1.1

Safety Information

• Storage Condition: Refrigerator

Pharmacology Properties

• Admin Routes: oral
• Bioavailability: >95%
• Excretion: Renal ; Lactic (In lactating females)
• Half Life: 12 hours
• Metabolism: Not metabolized
• Legal Status: Rx-only
• Pregnancy Category: B (US)

DETAILS

DrugBank - DB00489

• Drug Groups: approved
• Description: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [PubChem]
• Indication: For the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm. Also for the treatment of documented life-threatening ventricular arrhythmias.
• Pharmacology: Sotalol is an antiarrhythmic drug. It falls into the class of beta blockers (and class II antiarrhythmic agents) because of its primary action on the β-adrenergic receptors in the heart. In addition to its actions on the beta receptors in the heart, sotalol inhibits the inward potassium ion channels of the heart. In so doing, sotalol prolongs repolarization, therefore lengthening the QT interval and decreasing automaticity. It also slows atrioventricular (AV) nodal conduction. Because of these actions on the cardiac action potential, it is also considered a class III antiarrhythmic agent. The beta-blocking effect of sotalol is non-cardioselective, half maximal at about 80mg/day and maximal at doses between 320 and 640 mg/day. Sotalol does not have partial agonist or membrane stabilizing activity. Although significant beta-blockade occurs at oral doses as low as 25 mg, significant Class Ieffects are seen only at daily doses of 160 mg and above.
• Toxicity: The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycemia. In cases of massive intentional overdosage (2-16 grams) of sotalol the following clinical findings were seen: hypotension, bradycardia, cardiac asystole, prolongation of QT interval, Torsade de Pointes, ventricular tachy-cardia, and premature ventricular complexes.
• Affected Organisms: Humans and other mammals
• Biotransformation: Sotalol is not metabolized.
• Absorption: In healthy subjects, the oral bioavailability of sotalol is 90-100%. Absorption is reduced by approximately 20% compared to fasting when administered with a standard meal.
• Half Life: Mean elimination half-life is 12 hours. Impaired renal function in geriatric patients can increase the terminal elimination half-life.
• Protein Binding: Sotalol does not bind to plasma proteins.
• Elimination: Excretion is predominantly via the kidney in the unchanged form. Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk.
• References: Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP: Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet. 1996 Jul 6;348(9019):7-12. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - S677300

A potent α-adrenergic receptor antagonist. A class III antiarrythmic. It has been shown to prolong action potential and increases the refractory period.

REFERENCES

• Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP: Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet. 1996 Jul 6;348(9019):7-12. Pubmed
• Uloth, et al.: J. Med. Chem., 9, 88 (1966)
• Groh, W.J., et al.: Chirality, 5, 8 (1966)
• Pasnani, J.S., et al.: J. Pharmacol. Exp. Ther., 271, 184 (1966)