MEDICINAL CHEMISTRY

NHCOCH3) on the aromatic ring possess more antiarrhythmic activity than the analog
with an electron-withdrawing group (NO2).
(H 3C) 2CH
(H 3C) 2CH
NCH 2CH 2
N
C
Disopyramide (144)
O
CNH 2
Synthesis of Disopyramide (144)
CH 2CN
+
Br NaNH 2
N
Phenylacetonitrile 2-Bromopyridine (147)
(146)
CONH 2
C - (CH 2) 2 - N[CH(CH 3) 2] 2
N
Disopyramide (144)
H 2SO 4
COCH 2CH 2 N O
N
S
Moricizine (145)
CH-CN
N
NHCOOC 2H 5
Cl-(CH2) 2N[CH(CH3) 2] 2
2-(di-isopropylamino)-eth
yl chloride + NaNH2 CN
C - (CH2) 2 - N[CH(CH3) 2] 2
Disopyramide Phosphate (α-[2-(Diisopro pylamino) ethyl]-(x-phenyl-2-pyridine
acetamide phosphate) is approved for oral administration in the treatment of ventricular
arrhythmias as an alternative to quinidine and procainamide. It has both direct and
indirect actions of the heart, which resemble those of quinidine. Disopyramide is
administered as a racemic mixture, but its antiarrhythmic activity resides primarily in the
S-enantiomer. It is metabolised by mono-N-desalkylation with loss of one Nitroisopropyl
group. This metabolite is responsible for its anticholinergic actions.
Moricizine Hydrochloride (Ethyl 10-(3-morpholino nothiazine-2-carbamate
hydrochloride) (145). It causes frequency-dependent inhibition of the fast sodium ion
current during the action potential. It also shows conduction throughout the heart. It has
in particularly useful in patients with impaired cardiac function.
Therefore, it is contraindicated to patients with glaucoma, myasthenia gravis, or urinary
retention.
(149)
N
(148)