MEDICINAL CHEMISTRY

Encainide Hydrochloride: 4-Methoxy-2'-[2-(I-methyl-2-piperidyl) ethyl] benzanilide
hydrochloride (164) is similar pharmacologically to flecainide. However, its action after
long-term therapy seems to be affected by at least two active metabolites, Odemetliylencainide
(half-life 5 hours) and 3-methoxy-O-demethyl encainide. It is 12
times more active than quinidine. The benzanilido group seems to be essential for
activity. Replacement of 4-methoxy croup by 4-OH, 4-OAc, or 4-NH2 increases activity
dramatically. Introduction of additional methoxy groups, or substitution of methylthio or
chloro for 4-methoxy have decreased activity.
Indecainide (165) is structurally similar to aprindine and disopyramide. It has shown o
be highly efficacious and well treated antiarrhythmic drug for the suppression of
,entricular tachycardias. The principal metabolite of indecainide, Ndesisopropylndecainide,
has double half-life (18 hours) than the parent drug and has
substantial ntiarrhythmic activity. The activity is retained of the 9-carboxamido group is
,placed by a hydroxyl group.
Synthesis of Propafenone (169):
O
CH 2CH 2C
(170)
ONa
O CH 2CH 2C
ClH 2C CH 2
Epichlorohydrin
CH3-CH2-CH2-NH2
CH 2CH 2CO
O
(171)
Propafenone (169)
O
O CH 2CH CH 2
OH
OCH 2CHCH 2NHC 3H 7
Propafenone Hydrochloride: 2'-(2-Hydroxy-3-propyl amino propoxy)-3 -
phenylpropiophenone hydrochloride (169) is useful in supraventricular and ventricular
tachycardias and tachyarrhythmias. It resembles the β-adrenoceptor blockers of
aryloxypropanolamines. It is administered as a racemic mixture, wherein the Renantiomer
possesses the antiarrhythmic activity and the S-enantiomer is a non-selective
β-adrenergic antagonist. These complexities suggest that the drug should be used by only
expert cardiologists. It is metabolised to a 5-hydroxyl group attached to propiophenone
aryl ring and N-desalkylpropafenone. lntorduction of substituents in the β-phenyl ring (4-
CH3O, and (CH3)2N, 4-Cl) increases potency.
Class 11-Antiarrhythmic Drugs: β-Receptor antagonists (See antihypertensive agents)
Class II antiarrhythmic drugs are, β-adretiergic receptor blocking agents, which blocks
the role of the sympathetic nervous system in the genesis of certain cardiac arrhythmias.
Their dominant electrophysiological effect is to depress adrenergically enhanced calcium