SAR of Adrenergic blockers (Antagonist) (Beta blockers), Synthesis of Propranolol and Tolazoline

1. UNIT- II
Drugs acting on Autonomic nervous system
❖Adrenergic Antagonists synthesis
❖ SAR OF Beta Blockers
Dr P Parthiban
Professor
Vellalar college of Pharmacy

2. Propranolol
Propranolol is used to treat tremors,
angina (chest pain), hypertension
(high blood pressure), heart rhythm
disorders, and other heart or
circulatory conditions. It is also used
to treat or prevent heart attack, and
to reduce the severity and frequency
of migraine headaches.
Synthesis
1-Naphthol Epichlorohydrin
Propranolol
Isopropyl amine

3. Tolazoline
Tolazoline is a non-selective competitive α-adrenergic
receptor antagonist. It is a vasodilator that is used to
treat spasms of peripheral blood vessels.
Synthesis
Tolazoline

4. SAR of Beta blockers
Most of the beta blockers are in the chemical class of Aryloxypropanolamine
Two carbon chains are essential for the activity.
Secondary amines having optimal activity.

5. The configuration of the hydroxyl group bearing carbon of the aryloxypropanolamine side
chain play a critical role in the interaction of beta antagonist drugs with beta receptor.
The carbon must possess the S- configuration for optimal affinity to the beta receptor.
The enantiomer with the S- configuration is typically 100 times more potent.

6.  More lipophilic beta blockers enters the CNS much better than less lipophilic drug and
causes more CNS side effects.
 High lipophilicity: Propranolol, Labetalol.
 Intermediate lipophilicity: Metoprolol, Bisoprolol, Carvedilol, Acebutolol, Timolol, Pindolol.
 Low lipophilicity (also known as hydrophilic beta blockers): Atenolol, Nadolol, and Sotalol.
 Presence of amide group at the p-position of the aromatic ring retain selectivity for the
cardiac β1- receptors.eg: Atenolol, Labetalol etc.

7. THANK YOU