Conduct a thorough and mechanistic SAR analysis of the 3 therapeutic options in the case.
N-isopropyl group directs it toward the -receptors without any selectivity. 1 receptor
selectivity occurs with aryloxypropanolamines that have a para-substituted phenyl as the aryl
moiety. 1 receptor antagonists block the effects of epinephrine and norepinephrine on the heart
structure 1 is a Class II antiarrythmic, primarily affecting the SA and AV nodes slowing phase 4
depolarization and slowing SA node firing and AV node conduction prolonging repolarization.
cyclase causing an increase in cGMP. The cGMP activates kinases that phosphorylate myosin
light chain kinase, deactivating it and leading to vascular smooth muscle relaxation. The
formed from either cysteine or glutathione reaction. Organic nitrates are metabolized by
aryloxypropanolamine and one would expect it to have -adrenergic receptor blocking activity.
In addition, structure 3 has a phenylpropanone moiety ortho to the oxypropanolamine on the aryl
class 1C antiarrhythmic acting on ventricular tissue, blocking Na+ channels, slowing the rate of
Na+ dissociation, slowing phase 0 depolarization and slowing impulse conduction. Hepatic
Apply the chemical understanding gained from the SAR analysis to this patient’s specific
Structure 1 is propranolol. It would be a good choice as the second drug to help protect
SB from a silent ischemic heart attack. However, it would be a poor choice in this case since -
Structure 2 is isosorbide mononitrate. It would be the drug of choice in this case since it
is a long-acting organic nitrate, can be used in the diabetic patient, and has a different mechanism
of action for treating silent ischemic heart disease than the calcium channel blocker nifedipine.
Structure 3 is propafenone and would be a very poor choice in this case. It is primarily
used to treat ventricular and supraventricular arrhythmias. It does not have very significant -
adrenergic blocking action but could still affect SB’s blood glucose levels.