Dofetilide

Base Information

• Chemical Name: Dofetilide
• CAS No.: 115256-11-6
• Molecular Formula: C19H27N3O5S2
• Molecular Weight: 441.572
• Hs Code.: 2935904000
• European Community (EC) Number: 638-817-5
• UNII: R4Z9X1N2ND
• DSSTox Substance ID: DTXSID5046433
• Nikkaji Number: J291.759I
• Wikipedia: Dofetilide
• Wikidata: Q3712521
• NCI Thesaurus Code: C47499
• RXCUI: 49247
• Pharos Ligand ID: 1T1U6CGXR87B
• Metabolomics Workbench ID: 42608
• ChEMBL ID: CHEMBL473
• Mol file: 115256-11-6.mol

Synonyms:1-(4-methanesulfonamidophenoxy)-2-(N-(4-methanesulfonamidophenethyl)-N-methylamine)ethane;1-MSPMPE;dofetilide;Tikosyn;UK 68798;UK-68,798

Chemical Property of Dofetilide

Chemical Property:

• Appearance/Colour: white crystalline solid
• Vapor Pressure: 5.13E-15mmHg at 25°C
• Melting Point: 147-149 °C
• Refractive Index: 1.613
• Boiling Point: 614.1 °C at 760 mmHg
• PKA: 7.0, 9.0, 9.6(at 25℃)
• Flash Point: 325.2 °C
• PSA: 121.57000
• Density: 1.344 g/cm³
• LogP: 4.29050
• Storage Temp.: Store at RT
• Solubility.: DMSO: >20mg/mL
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 11
• Exact Mass: 441.13921332
• Heavy Atom Count: 29
• Complexity: 672

Purity/Quality:

99%, ^*data from raw suppliers

Dofetilide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,N
• Hazard Codes: T,N
• Statements: 61-48/22-51
• Safety Statements: 53-22-36-57

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiarrhythmic Agents
• Canonical SMILES: CN(CCC1=CC=C(C=C1)NS(=O)(=O)C)CCOC2=CC=C(C=C2)NS(=O)(=O)C
• Recent ClinicalTrials: Improvement in Endothelial Dysfunction After Initiation of Anti-arrhythmic Therapy in Atrial Fibrillation Patients
• Description: Dofetilide was launched in the US as a novel class III antiarrhythmic for treatment of cardiac patients with highly symptomatic atrial fibrillation This bisarylsulfonamide can be obtained by a three step synthesis starting from 4-nitro-N-methylphenethylamine and involving simultaneous nitro reduction and mesylation on both aromatic amine functions. In contrast to other class III antiarrhythmic agents such as amiodarone, dofetilide potently and selectively inhibits a single potassium channel, Ikr, the rapidly acting component of the delayed rectifier potassium current, Accordingly, by blocking the open state of Ikr, dofetilide is able to prolong the effective refractory period (ERP) in both atrial and ventricular myocardium and the monophasic action potential duration. Moreover, as it targets only one cardiac ion channel, it does not produce any effects on the sinus node, cardiac conduction system and other extracardiac organs, making it unique among established class III agents. Several pharmacological studies with models using different animal species indicated that dofetilide was a potent and highly selective class III antiarrhythmic agent devoid of cardiodepressive effects. During clinical trials in patients with paroxysmal atrial or supraventricular fibrillation, dofetilide was found to increase atrial and ventricular refractory periods without affecting conduction or sinus node function. If increases in the QT/QTc interval after oral or intravenous dofetilide are expected, as for other class III antiarrhythmic agents, other electrocardiographic intervals are unaffected.
• Uses: Potassium channel blocker Dofetilide (90%) , is a potassium channel blocker. Antidysrhythmic drug.
• Therapeutic Function: Antiarrhythmic
• Clinical Use: Dofetilide (Tikosyn) is a “pure” class III drug. It prolongs the cardiac action potential and the refractory period by selectively inhibiting the rapid component of the delayed rectifier potassium current (IKr). Dofetilide is approved for the treatment of atrial fibrillation and atrial flutter. Because of the lack of significant hemodynamic effects, dofetilide may be useful in patients with CHF who are in need of therapy for supraventricular tachyarrhythmias. Dofetilide is not indicated for use in the setting of ventricular arrhythmias.
• Drug interactions: Verapamil increases serum dofetilide levels, as do drugs that inhibit cationic renal secretion, such as ketoconazole and cimetidine, raise serum levels.

Technology Process of Dofetilide

There total 12 articles about Dofetilide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 92.3%

methanesulfonyl chloride (124-63-0) + 1-(4-methanesulphonamidophenoxy)-2-[N-methyl-N-(4-aminophenethyl)amino]ethane (115256-12-7) → dofetilide (115256-11-6)

Guidance literature:

With triethylamine; In dichloromethane; at 0 ℃;

DOI:10.1016/S0960-894X(00)00412-1

Reference yield: 91.0%

methanesulfonamide (3144-09-0) + N-(4-chlorophenethyl)-2-(4-chlorophenoxy)-N-methylethanamine (1197186-15-4) → dofetilide (115256-11-6)

Guidance literature:

With bis(η3-allyl-μ-chloropalladium(II)); potassium carbonate; tert-butyl XPhos; In 2-methyltetrahydrofuran; at 80 ℃; Inert atmosphere;

DOI:10.1021/ol200660s

Reference yield: 51.0%

1-(4-aminophenoxy)-2-[N-(4-aminophenethyl)-N-methylamino]ethane (115256-13-8) + Methanesulfonic anhydride (7143-01-3) → dofetilide (115256-11-6)

Guidance literature:

In dichloromethane; Ambient temperature;

DOI:10.1021/jm00166a011

upstream raw materials:

1-(4-aminophenoxy)-2-[N-(4-aminophenethyl)-N-methylamino]ethane

Methanesulfonic anhydride

methanesulfonyl chloride

1-(4-methanesulphonamidophenoxy)-2-[N-methyl-N-(4-aminophenethyl)amino]ethane

Downstream raw materials:

Dofetilide N-oxide

Refernces

• 1、 Rosen, Brandon R.,Ruble, J. Craig,Beauchamp, Thomas J.,Navarro, Antonio. "Mild Pd-catalyzed N -arylation of methanesulfonamide and related nucleophiles: Avoiding potentially genotoxic reagents and byproducts". supporting information; experimental part. p. 2564 - 2567. Retrieved 2011/06/25.
• 2、 -. "Dofetilide polymorphs". . . Retrieved 2008/06/13.