MEDICINAL CHEMISTRY

Structure-activity Relationships of β-adrenergic antagonist
Shortly thereafter, a major innovation in drug development for the β -adrenergic
antagonists was introduced when it was discovered that an oxymethylene bridge,OCH2,
could be inserted into the arylethanolamine structure of pronethalol to afford propranolol
(53), an aryl-substituted phenyloxypropanololamines and the first clinically successful
practolol, which selectively inhibited sympathetic β-blocker. Note that, along with the
introduction of the Oxymethylene Bridge, the side chain has been moved from C2 of the
naphthyl group to the Cl position.
O
OH
N H
Propranolol (53)
In general, aryloxypropanolamines are more potent β-blockers than the corresponding
arylethanolamines and most of β-blockers currently used clinically are
aryloxypropanolamines. β-blockers have found wide use in treating hypertension.
4. Cardiac Glycosides
Introduction
The cardiac glycosides are an important class of naturally occurring drugs whose actions
include both beneficial and toxic effects on the heart. Their desirable cardiotonic action
is of particular benefit in the treatment of congestive heart failure and associated edema
and their preparations have been used as medicinal agents as well as poisons since 1500
B.C. This dual application serves to highlight the toxic potential for this class of lifesaving
drugs.
The cardio active steroids and their glycosides are widely distributed in nature and have
characteristic actions on contractility and electrophysiology of heart. Their discovery is
an example of folk lore medicine, known to ancient people like Romans and Egyptians.
Most glycosides are obtained from leaves of the foxglove, Digitalis purpurea or Digitalis
lanata. William Withering (1785) was the first to notice their effects on heart; cardiac
glycosides are the combination of an aglycone or genin, and one to four sugars. The
steroidal aglycone of the glycosides is responsible for cardiac activity and sugars provide
favorable solubility and distribution, and thus, affect its potency and duration of action.
Now these glycosides are used less frequently. Patients are generally treated with
calcium channel blockers (verapamil), Acetyl Choline Esterase Inhibitors (ACEIs) and
diuretics.
Classification of Cardiac Glycosides
1. Cardenolides (107)
2. Bufadenolides (108)
CH 3
CH 3