MEDICINAL CHEMISTRY

conduction velocity, and decrease spontaneous diastolic depolarization in pacemaker
cells. The decrease in diastolic depolarization tends to suppress ectopic foci activity.
Prolongation of the refractory period tends to abolish reentry arrhythmias. This class is
further subclassified into class IA, IB, and IC based on the primary pharmacologic effect.
Class IA Antiarrhythmic Drugs
H 3CO
6'
H
HO
C N
9
H
8
N
H
Quinidine (138)
CH=CH 2
H
CONHCH 2CH 2N
NH 2
Procainamide (139)
Quinidine (138) is a d-isomer of quinine. It is obtained from bark of various species of
cinchona and from Remijia pendunculata. Quinidine has a direct myocardial depressant
action. It increases refractory period, depresses contractility, depresses excitability and
slows speed of conduction in cardiac muscle.
Synthesis of Procainamide (139)
COOH
NO 2
SOCl 2
p-Nitrobenzoic acid
(140)
COCl
NO 2
(141)
-HCl
+ H2NCH2CH2N(C2H5) 2
+ -
CONH(CH2) 2-N(C2H5) 2Cl
NH 2
Procainamide (139)
C 2H 5
C 2H 5
CONH(CH 2) 2-N(C 2H 5) 2
NO 2
(1) Sn/HCl
(2) HCl
Procainamide (p-Amino-N-[2diethylamino)-ethyl] benzamide hydrochloride) (139)
differs from local anaesthetic procaine in that the ester linkage of procaine is replaced by
an amide linkage. This difference had distinct advantages as an antiarrhythmic drug, that
is, greater stability from enzymatic hydrolysis and fewer CNS effects of procaine.
Procainamide is so similar in its action to quinidine that the two drugs can be used
interchangeably. It is particularly effective in promptly abolishing ventricular premature
depolarization and paroxysmal ventricular tachycardia. Acute glaucoma and urinary
retention is observed. Procainamide analogs with electron-donating groups (OH, NH2,
(142)