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Dofetilide

Dofetilide Structure
Dofetilide
  • CAS No.115256-11-6
  • Chemical Name:Dofetilide
  • CBNumber:CB3381832
  • Molecular Formula:C19H27N3O5S2
  • Formula Weight:441.56
  • MOL File:115256-11-6.mol
Dofetilide Property
  • Melting point 147-1490C
  • Boiling point 614.1±65.0 °C(Predicted)
  • Density 1.344±0.06 g/cm3(Predicted)
  • storage temp. 2-8°C
  • solubility DMSO: >20mg/mL
  • pka 7.0, 9.0, 9.6(at 25℃)
  • form powder
  • color white to off-white
  • Stability Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
  • InChIKey IXTMWRCNAAVVAI-UHFFFAOYSA-N
  • CAS DataBase Reference 115256-11-6(CAS DataBase Reference)
  • FDA UNII R4Z9X1N2ND
  • ATC code C01BD04
  • UNSPSC Code 41116107
  • NACRES NA.77
Safety
Hazard and Precautionary Statements (GHS)
  • Symbol(GHS)
  • Signal wordDanger
  • Hazard statements H302-H360
  • Precautionary statements P201-P202-P264-P270-P301+P312-P308+P313
Dofetilide Price More Price(2)
  • Brand: Sigma-Aldrich(India)
  • Product number: PZ0016
  • Product name : Dofetilide
  • Purity: ≥98% (HPLC)
  • Packaging: 5MG
  • Price: ₹15891.1
  • Updated: 2022/06/14
  • Buy: Buy
  • Brand: Sigma-Aldrich(India)
  • Product number: PZ0016
  • Product name : Dofetilide
  • Purity: ≥98% (HPLC)
  • Packaging: 25MG
  • Price: ₹63477.8
  • Updated: 2022/06/14
  • Buy: Buy

Dofetilide Chemical Properties,Usage,Production

  • 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.
  • Chemical Properties White Crystalline Solid
  • Originator Pfizer (US)
  • Uses Dofetilide (90%) , is a potassium channel blocker. Antidysrhythmic drug.
  • Definition ChEBI: A tertiary amino compound that is N-ethyl-N-methylethanamine substituted by a 4-[(methylsulfonyl)amino]phenoxy and a 4-[(methylsulfonyl)amino]phenyl group at the terminal carbon atoms respectively. It is used as an an i-arrhythmia drug.
  • Manufacturing Process To a solution of N-methyl-4-nitrophenethylamine (1.5 g) (J.O.C., [1956], 21, 45) and 2-[4-nitrophenoxy]ethyl chloride (1.55 g) (C.A., [1955], 49, 3163e) in acetonitrile (50 ml) was added potassium carbonate (1.25 g) and sodium iodide (1.2 g) and the suspension was stirred at reflux for 72 hours. After evaporation to dryness, the residual oily solid was partitioned between a 2 N aqueous sodium bicarbonate solution and ethyl acetate. After two further extractions with ethyl acetate, the organic portions were combined, washed with a saturated aqueous brine solution, dried over magnesium sulfate, filtered and evaporated. The resultant orange solid (2.7 g) was crystallised from ethanol to give 1-(4-nitrophenoxy)-2-[N-methyl-N-(4- nitrophenethyl)amino]ethane (1.9 g), m.p. 74°C.
    A solution of 1-(4-nitrophenoxy)-2-[N-methyl-N-(4- nitrophenethyl)amino]ethane (1.5 g) in ethanol (100 ml) was stirred for 16 hours at room temperature under three atmospheres of hydrogen in the presence of Raney nickel. The reaction mixture was filtered and evaporated to dryness. The residual oil was re-dissolved in ether, filtered and evaporated to give a yellow solid (1.1 g), which was crystallised from ethyl acetate/petroleum ether (b.p. 60-80°C) to give 1-(4-aminophenoxy)-2-[N-(4- aminophenethyl)-N-methylamino]ethane (0.9 g), m.p. 73-74°C.
    A solution of 1-(4-aminophenoxy)-2-[N-(4-aminophenethyl)-Nmethylamino]ethane (0.75 g) and methanesulphonic anhdyride (1.0 g) in dry methylene chloride (50 ml) was stirred at room temperature overnight. After evaporation, the resultant oil was partitioned between a 2 N aqueous sodium bicarbonate solution and ethyl acetate. After two further extractions with ethyl acetate, the organic portions were combined, dried over magnesium sulfate, filtered and evaporated. The resultant colourless solid (1.2 g) was crystallised from ethyl acetate/methanol to give methanesulfonamide, N-(4-(2-(methyl(2- (4-((methylsulfonyl)amino)phenoxy)ethyl)amino)ethyl)phenyl)-, (0.6 g), m.p. 147-149°C.
  • brand name Tikosyn (Pfizer).
  • Therapeutic Function Antiarrhythmic
  • General Description Dofetilide, N-[4-(3-{[2-(4-methanesulfonylaminophenyl)ethyl]methylamino}propoxy)phenyl]methane-sulfonamide (Tikosyn), acts by blocking thecardiac ion channel carrying the rapid component of thedelayed rectifier potassium currents (Ikr) and is used toterminate supraventricular arrhythmias, prevent the recurrenceof atrial fibrillation, and treat life-threatening ventriculararrhythmias. Unlike sotalol and ibutilide, whichare also methanesulfonanilides, it has no effect on adrenergicreceptors or sodium channels, respectively. Dofetilidehas high specificity for the delayed rectifier potassiumcurrents.
  • Biological Activity Selective potassium channel blocker. Blocks hERG K + channels; inhibits the rapid delayed-rectifier K + current (I Kr ). Displays class III antiarrhythmic properties.
  • Biochem/physiol Actions Dofetilide is a Class III antiarrhythmic and hERG channel blocker. Dofetilide selectively blocks the rapid component of the delayed rectifier outward potassium current (IKr).
  • 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.
  • Side effects The incidence of noncardiac adverse events is not different from that of placebo in controlled clinical trials. The principal cardiac adverse effect is the risk of torsades de pointes due to QT prolongation.The risk is approximately 3%, and most cases are observed in the first 3 days of therapy.As such, initiation of therapy should be performed with the patient in hospital.
  • Drug interactions Verapamil increases serum dofetilide levels, as do drugs that inhibit cationic renal secretion, such as ketoconazole and cimetidine, raise serum levels.
  • Metabolism Dofetlide is used orally to suppress atrial fibrillation and flutter. It is more potent and selective than other Class III methanesulfonanilides, including sotalol. Dofetilide is well absorbed from the gastrointestinal tract, with a bioavailability of 96 to 100%. The bioavailability of oral dofetilide is not affected by food or antacids. Protein binding is 60 to 70%. Dofetilide is metabolized by the hepatic CYP3A4 enzyme system via N-dealkylation and N-oxidation to inactive or minimally active metabolites. Of the approximately 80% of a dose excreted in urine, approximately 80% is excreted unchanged, with the other 20% as metabolites.
  • storage Room temperature
  • Precautions Contraindications include baseline prolongation of the QT interval, use of other QT-prolonging drugs; history of torsades de pointes; a creatinine clearance of less than 20 mL/minute; simultaneous use of verapamil, cimetidine, or ketoconazole; uncorrected hypokalemia or hypomagnesemia; and pregnancy or breast-feeding.
  • References 1) Gwilt et al. (1991) UK-68,798: a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells; J. Pharmacol. Exp. Ther., 256 318 2) Snyders and Chaudhary, (1996) High affinity open channel block by dofetilide of HERG expressed in a human cell line; Mol. Pharmacol., 49 949
Dofetilide Preparation Products And Raw materials
Raw materials
Preparation Products
Dofetilide Suppliers
Global(326)Suppliers
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Dofetilide Spectrum
115256-11-6, DofetilideRelated Search:
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  • 多非利特系列
  • C19H27N3O5S2
  • 15256-11-6
  • 115226-11-6
  • 多非利特,10 MM DMSO 溶液
  • DOFETILIDE,HERG K+ CHANNEL BLOCKER
  • N-(4-(2-(甲基(2-(4-(甲基磺酰胺基)苯氧基)乙基)氨基)乙基)苯基)甲磺酰胺
  • 多非利特 USP标准品
  • 多非利特杂质
  • N-[4-(2-{2-[4-(甲磺酰胺基)苯氧基]-N-甲基乙基氨基}乙基)苯基]-甲磺酰胺
  • N-[4-[2-[甲基[2-[4-[(甲磺酰基)氨基]苯氧基]乙基]氨基]乙基]苯基]甲磺酰胺
  • 多菲菜德
  • DOFETILIDE 多非利特
  • 多非利特
  • 多菲利特
  • 4-(2-氯乙氧基)硝基苯
  • 2-[4-硝基苯氧基]氯乙烷
  • 115256-11-6
  • Dofetilide - Bio-X ?
  • DOFETILIDE USP
  • Dofetilide, 10 mM in DMSO
  • Dofetilide, hERG K+ channel blocker
  • Dofetilide Impurity
  • Dofetilide (1224937)
  • DofetilideQ: What is Dofetilide Q: What is the CAS Number of Dofetilide Q: What is the storage condition of Dofetilide Q: What are the applications of Dofetilide
  • Dofetilide (UK 68789)
  • N-(4-(2-(Methyl(2-(4-(methylsulfonamido)phenoxy)ethyl)amino)ethyl)phenyl)methanesulfonamide
  • Dofetilide (>90%)

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