MEDICINAL CHEMISTRY

Synthesis of Moricizine:
(153)
H
N NH2 H
N
ClCO2C2H5
COCH2CH2Cl N
NHCO2C2H5 ClCH2CH2COCl
S
(150)
HN O
COCH 2CH 2 N O
N
S
Ethylchloroformate
NHCO 2C 2H 5
.HCl
Moricizine (145)
H
N
S
(152)
S 2/I 2/Heat
NHCO 2C 2H 5
(151)
NHCO 2C 2H 5
Structure activity relationship
(1) Substitution at the ortho position improved the biological activity. Ethyl group is
optimal.
(2) Replacement of pyridyl group with acylic amines gave good compounds.
Cyclohexyl group gave equally potent compound. Pentenamide showed a longer duration
of action than disopyramide.
(3) 2-Pyridyl is more potent than other isomers.
(4) Variation in the amino group only di-isopropylamine and 2, 6dimethylpiperidine
were the most suitable groups.
(5) A correlation between n values and ventricular arrhythmias was obtained.
Class IB Antiarrhythmic Drugs
CH 3
O
H
N C
CH 3
Lidocaine (154)
H 2
C N
C 2H 5
C 2H 5
C 6H 5
C 6H 5
O
N
H
NH
O
Phenytoin (155)
Lidocaine (154) is similar to procaine, is an effective, clinically used local. Its cardiac
effects, however, are distinctly different from those of procainamide or quinidine.
Lidocaine is normally reserved for the treatment of ventricular arrhythmias and is, in fact,
usually the drug of choice for emergency treatment of ventricular arrhythmias. Its utility
in these situations is due to the rapid onset of antiarrhythmic effects on intravenous
infusion. In addition, these effects cease soon after the infusion is terminated. Thus,
lidocaine therapy may be rapidly modified in response to changes in the patient's status.