Chemistry Reference
In-Depth Information
Racemic Drugs with one Major Bioactive Enantiomer
In this group, there are a number of cardiovascular drugs, agents widely used for the treatment of hypertension, heart
failure, arrhytmias, and other diseases. Among these are the -adrenergic blocking agents, calcium channel
antagonists and angiotensin-converting enzyme (ACE) inhibitors. The majority of racemic pharmaceuticals have one
major bioactive enantiomer (called eutomer), the other is inactive or less active (called distomer) or toxic or can
exert other desired or undesired pharmacological properties.
Levorotary-isomer of all -blockers is more potent in blocking -adrenoceptors than their dextrorotary-isomer, such
as (
S
)-(-)-propranolol (Fig.
2
) 100 times more active than its (
R
)-(+)-antipode [12,13]. A number of -blockers are
still marketed as racemic forms such as acebutolol, atenolol, alprenolol, betaxolol, carvedilol, metoprolol, labetalol,
pindolol, etc., except timolol and penbutolol (Fig.
2
) that are used as single (S)-(-)-isomers.
OH
H
N
O
H
2
N
O
N
H
O
OH
O
O
N
H
NH
OH
Atenolol
(
S
)-(-)-Propranolol
Acebutolol
O
O
O
N
H
O
OH
O
O
N
H
N
H
O
N
H
OH
OH
Alprenolol
Betaxolol
Carvedilol
OH
H
N
O
N
H
O
O
N
H
OH
HO
OH
N
H
O
2
Metoprolol
Labetalol
Pindolol
O
N
N
N
H
S
O
O
N
H
OH
N
OH
(
S
)-(-)-Penbutolol
(
S
)-(-)-Timolol
Figure 2:
Racemic drugs with one major bioactive enantiomer (-blockers).
Many calcium channel antagonists are used under racemic form such as verapamil, nicardipine, nimodipine,
nisoldipine, felodipine, manidipine…, except diltiazem (Fig.
3
) that is a single (
S,S
)-(+)-isomer.
For example, the pharmacological potency of (
S
)-(-)-verapamil is 10-20 times greater than its (
R
)-(+)-antipode in
terms of negative chromotropic effect on auricoventricular (AV) conduction and vasodilatator in man and animals
[14,15].
All ACE inhibitors such as captopril, benazepril, enalapril, imidapril (Fig.
3
) are diastereoisomeric compounds and
most of them are marketed as single isomers. Valsartan, an angiotensin II receptor antagonist, is used as its (
S
)-
enantiomer and the activity of the (
R
)-enantiomer is clearly lower than the (
S
)-enantiomer (Fig.
4
) [16].
