54143-56-5

Usage

Uses

Used in Pharmaceutical Industry:
Flecainide acetate is used as a class I antiarrhythmic agent for regulating heartbeats of the upper and lower heart chambers. It acts as a sodium channel blocker and is effective in treating ventricular tachycardias and ventricular arrhythmias.
Flecainide acetate is used as an anti-arrhythmic agent for slowing down an overactive heart, helping to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart).
Additionally, Flecainide acetate is used to inhibit hERG potassium channels at clinically relevant concentrations, which contributes to its antiarrhythmic properties.

Biological Activity

Open Na + channel blocker that inhibits fast Na + current in cardiac muscle in a use- and concentration-dependent manner. Orally-active class Ic antiarrhythmic agent.

Biochem/physiol Actions

Class IC antiarrhythmic agent; sodium channel blocker

Clinical Use

#N/A

Drug interactions

Potentially hazardous interactions with other drugs Anti-arrhythmics: concentration increased by amiodarone - halve dose of flecainide; increased myocardial depression with other anti-arrhythmics. Antidepressants: concentration increased by fluoxetine; increased risk of ventricular arrhythmias with tricyclics. Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid. Antihypertensives: increased myocardial depression and bradycardia with beta-blockers; increased myocardial depression and asystole with verapamil. Antimalarials: concentration increased by quinine; avoid with artemether/lumefantrine. Antimuscarinics: increased risk of ventricular arrhythmias with tolterodine. Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval and phenothiazines; increased risk of arrhythmias with clozapine. Antivirals: concentration possibly increased by fosamprenavir, indinavir, lopinavir, ritonavir and saquinavir, increased risk of ventricular arrhythmias - avoid; use telaprevir with caution. Diuretics: increased cardiac toxicity if hypokalaemia occurs.

Metabolism

Flecainide is extensively metabolised (subject to genetic polymorphism), the 2 major metabolites being m-Odealkylated flecainide and m-O-dealkylated lactam of flecainide, both of which may have some activity. Its metabolism appears to involve the cytochrome P450 isoenzyme CYP2D6, which shows genetic polymorphism.Flecainide is excreted mainly in the urine, approximately 30% as unchanged drug and the remainder as metabolites. About 5% is excreted in the faeces. Haemodialysis removes only about 1% of unchanged flecainide.

References

1) Rouet and Ducouret (1994), Use- and concentration-dependent effects of flecainide in guinea pig right ventricular muscle; J. Cardiovasc. Pharmacol.,?24?177 2) Singh?et al. (1984),?The electrophysiology and pharmacology of verapamil, flecainide, and amiodarone: correlations with clinical effects and antiarrhythmic actions; Ann. N.Y. Acad. Sci.,?432?210 3) Banitt?et al.?(1977),?Anti-arrhythmics. 2. Synthesis and antiarrhythmic activity of N-(piperidylalkyl)trifluoroethoxybenzamides; J. Med. Chem.,?20?821 4) Melgari?et al.?(2015),?Molecular basis of hERG potassium channel blockade by the class Ic antiarrhythmic flecainide; J. Mol. Cell. Cardiol.,?86?42

InChI:InChI=1/C17H20F6N2O3.C2H4O2/c18-16(19,20)9-27-12-4-5-14(28-10-17(21,22)23)13(7-12)15(26)25-8-11-3-1-2-6-24-11;1-2(3)4/h4-5,7,11,24H,1-3,6,8-10H2,(H,25,26);1H3,(H,3,4)

Upstream product

• 57415-36-8 2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide 
• 64-19-7 acetic acid 
• 54143-55-4 flecainide 

Relevant academic research and scientific papers

Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)-benzamide and salts thereof

A process for the preparation of Flecainide acetate, its salts, in particular its pharmaceutically acceptable salts, and intermediates thereof is described wherein 2,5-dibromotoluene is used as a starting material. The method involves a technique for preparing the starting material 2,5-bis(2,2,2-trifluroethoxy)toluene in high yields by reacting 2,5-dibromotoluene with 2,2,2-trifluoroethanol in the presence of a base and a copper-containing catalyst.

Preparation of acid addition salts of amine bases by solid phase-gas phase reactions

A process for the preparation of an acid addition salt of an organic base comprising exposing the organic base in solid form to a gaseous acid, with the proviso that ziprasidone, its acid addition salts and intermediates thereof are excluded.

Novel process for the preparation of flecainide, its pharmaceutically acceptable salts and important intermediates thereof

Process for the preparation of Flecainide, its pharmaceutically acceptable salts and important intermediates thereof that involves the use of the 2-halobenzoic acid and its derivatives as a starting material. The use of this process also allows for the synthesis of a novel intermediate useful in the production of Flecainide. This new process is an inexpensive and efficient process for the manufacture of these compounds.

α,α-dibromo-α-chloro-acetophenones as synthons

This disclosure relates to the use of α,α-dibromo-α-chloroacetophenone compounds as intermediates for the preparation of aromatic carbonyl compounds, especially aromatic amides. The compound 2,5-bis(2,2,2-trifluoroethoxy)-α,α-dibromo-α-chloroacetophenone is especially useful as an intermediate for the preparation of flecainide, a known pharmaceutical.

Process for the preparation of derivatives of pyrrolidine and piperidine

Processes and intermediates for the preparation of the antiarrhythmic agent 2,5-bis(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamide.