Dofetilide

Dofetilide 속성

Dofetilide MSDS

Dofetilide

Dofetilide C화학적 특성, 용도, 생산

개요

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.

화학적 성질

White Crystalline Solid

용도

Dofetilide (90%) , is a potassium channel blocker. Antidysrhythmic drug.

정의

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.

일반 설명

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.

생물학적 활성

Selective potassium channel blocker. Blocks hERG K + channels; inhibits the rapid delayed-rectifier K + current (I Kr ). Displays class III antiarrhythmic properties.

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.

부작용

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.

신진 대사

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.

주의 사항

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.

Dofetilide 준비 용품 및 원자재

원자재

준비 용품

Dofetilide 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Hebei Yanxi Chemical Co., Ltd.	+8617531190177	peter@yan-xi.com	China	5993	58
Henan Bao Enluo International TradeCo.，LTD	+86-17331933971 +86-17331933971	deasea125996@gmail.com	China	2503	58
Shaanxi Haibo Biotechnology Co., Ltd	+undefined18602966907	qinhe02@xaltbio.com	China	1000	58
Anhui Zhongda Biotechnology Co., Ltd	+8619956560829	justine@zhongda-biotech.com	China	300	58
Wuhan Xinhao Biotechnology Co., Ltd	+86-18120578002 +86-18120578002	xinhao-6@xinhaoshengwu.com	China	350	58
Beijing Cooperate Pharmaceutical Co.,Ltd	010-60279497	sales01@cooperate-pharm.com	CHINA	1811	55
Henan Tianfu Chemical Co.,Ltd.	+86-0371-55170693 +86-19937530512	info@tianfuchem.com	China	21695	55
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32480	60
career henan chemical co	+86-0371-86658258	sales@coreychem.com	China	29914	58
Zhejiang ZETian Fine Chemicals Co. LTD	18957127338	stella@zetchem.com	China	2141	58

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