54143-55-4 Usage
Description
Flecainide is a synthetic antiarrhythmic drug, chemically described as a monocarboxylic acid amide derived from the formal condensation of 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with the primary amino group of piperidin-2-ylmethylamine. It is an analog of procainamide, with a 2.2.2-trifluoroethoxyl group added at C2 and C3 of the benzene ring and a diaminoethyl side chain attached to the piperidine ring. Flecainide is characterized by its white crystalline powder appearance and is used to prevent and treat tachyarrhythmia, which is an abnormal fast rhythm of the heart.
Uses
Used in Cardiology:
Flecainide is used as an antiarrhythmic agent in the form of its acetate salt for the prevention and treatment of tachyarrhythmia. It is classified as a class IC antiarrhythmic, which means it works by blocking both the fast and slow sodium channels in the heart, thus stabilizing the heart rhythm.
Used in Ventricular Arrhythmia Treatment:
Flecainide is utilized as a treatment for naturally occurring ventricular arrhythmia, a condition characterized by irregular and rapid heartbeats originating in the ventricles of the heart. Its application helps to regulate the heart's rhythm and prevent potentially life-threatening complications.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Flecainide is used as an active pharmaceutical ingredient (API) for the development of medications aimed at treating various types of arrhythmias. Its chemical properties and antiarrhythmic effects make it a valuable component in the formulation of heart rhythm regulation drugs.
Originator
Tambocor,Kettelhack Riker,W. Germany,1982
Manufacturing Process
Under a nitrogen atmosphere 2-aminomethylpiperidine (0.249 mol, 28.4 g) is
treated dropwise over 25 minutes with 2,2,2-trifluoroethyl 2,5-bis(2,2,2-
trifluoroethoxy)benzoate (0.0249 mol, 10.0 g). After 3 hours 50 ml of
benzene is added to the thick mixture and stirred for about 40 hours at 45°C.
The mixture is then concentrated under vacuum with heating to remove the
volatile components. The residue solidifies after cooling, is steam distilled for
further purification and is separated by filtration and extracted into
dichloromethane. The dichloromethane solution is washed with saturated
sodium chloride solution, and the organic layer is dried over anhydrous
magnesium sulfate. The magnesium sulfate is removed by filtration and 4 ml
of 8.4 N hydrogen chloride in isopropanol is added to the dichloromethane
solution with stirring.After 2 hours the mixture is cooled to about 0°C and the crude product is
collected by filtration, washed with diethyl ether and dried in a vacuum oven.
After treatment with decolorizing charcoal and recrystallization from an
equivolume mixture of isopropanol and methanol, the product, 2,5-bis(2,2,2-
trifluoroethoxy)-N-(2-piperidylmethyl)benzamide hydrochloride has a MP of
228°C to 229°C.
Therapeutic Function
Antiarrhythmic
World Health Organization (WHO)
The membrane-stabilizing antiarrhythmic agent flecainide was
introduced into medicine in 1982. The decision to delete the indications for
patients with asymptomatic and less severe symptomatic ventricular arrhythmias
was taken on the basis of the results of a trial (CAST study) that showed a two-fold
increase in deaths in post-myocardiac patients taking flecainide compared with the
placebo group.
Hazard
Human systemic effects.
Clinical Use
Flecainide (Tambocor) is a fluorinated aromatic hydrocarbon
examined initially for its local anesthetic
action and subsequently found to have antiarrhythmic
effects. Flecainide inhibits the sodium channel, leading
to conduction slowing in all parts of the heart, but
most notably in the His-Purkinje system and ventricular
myocardium. It has relatively minor effects on repolarization.
Flecainide also inhibits abnormal automaticity.
Flecainide is effective in treating most types of atrial arrhythmias.
It is also used for life-threatening ventricular
arrhythmias. However, flecainide should be used with extreme
caution in any patient with structural heart disease.
Flecainide crosses the placenta, with fetal levels reaching
approximately 70% of maternal levels. In many centers,
it is the second-line drug after digoxin for therapy of fetal
arrhythmias. Because of the high incidence of proarrhythmia,
initiation of therapy or significant increases in
dosing should be performed only on inpatients.
Side effects
Most adverse effects occur within a few days of initial
drug administration. The most frequently reported effects
are dizziness, light-headedness, faintness, unsteadiness,
visual disturbances, blurred vision (e.g., spots before
the eyes, difficulty in focusing), nausea, headache,
and dyspnea.
Worsening of heart failure and prolongation of the PR
and QRS intervals are likely to occur with flecainide, and
an increased risk of proarrhythmia has been reported.
Synthesis
Flecainide, N-(2-piperidylmethyl)-2,5-bis-(2,2,2-trifluoroethoxy)benzamide
(18.1.14), is synthesized from 2,5-dihydroxybenzoic acid. Reacting this with trifluoroethylfluoromethylsulfonate
gives 2.2.2-trifluoroethoxylation of all three hydroxyl groups, to produce
2,2,2-trifluoroethyl ester of 2,5-bis-(2,2,2-trifluoroethoxy)benzoic acid (18.1.12).
Reacting this with 2-aminomethylpiridine gives the corresponding amide (18.1.13), which
upon reduction of the pyridine ring with hydrogen gives flecainide (18.1.14).
Drug interactions
In patients whose condition has been stabilized by flecainide,
the addition of cimetidine may reduce the rate
of flecainide’s hepatic metabolism, increasing the potential
for toxicity. Flecainide may increase digoxin concentrations
on concurrent administration.
Precautions
Flecainide is contraindicated in patients with preexisting
second- or third-degree heart block or with bundle
branch block unless a pacemaker is present to maintain
ventricular rhythm. It should not be used in patients
with cardiogenic shock.
Check Digit Verification of cas no
The CAS Registry Mumber 54143-55-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,4,1,4 and 3 respectively; the second part has 2 digits, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 54143-55:
(7*5)+(6*4)+(5*1)+(4*4)+(3*3)+(2*5)+(1*5)=104
104 % 10 = 4
So 54143-55-4 is a valid CAS Registry Number.
InChI:InChI=1/C17H20F6N2O3/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/h4-5,7,11,24H,1-3,6,8-10H2,(H,25,26)
54143-55-4Relevant articles and documents
Novel process for the preparation of flecainide, its pharmaceutically acceptable salts and important intermediates thereof
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Page/Page column 4-5, (2010/02/11)
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.
Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-n-(2-piperidyl-methyl)-benzamide (flecanide)
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, (2008/06/13)
Process for the synthesis of FLECAINIDE comprising the reaction between 2,5-dihydroxybenzoic acid with trifluoroethanol perfluorobutanesulphonate to give the intermediate trifluoroethanol 2,5-bis-trifluoroethoxybenzoate, the reaction of said intermediate with 2-aminomethylpiperidine to give FLECAINIDE.