Tolazoline

IUPAC nomenclature

2-Benzyl-4,5-dihydro-1H-imidazole.

Classification

Tolazoline is nonselective α-adrenergic antagonist.

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES

1 Molecular weight 160.22 g/mol

2 Physical appearance Present in solid form

3 Melting point 174°C

4 Solubility 373 mg/L

5 Octanol/water partition coefficient 2.65

6 Presence of ring Benzene and imidazole

7 Number of chiral centers Not present

Mechanism of Action
Tolazoline has moderate α-adrenergic antagonist property and also having histamine agonist
activity.

It produces vasodilation through direct effect on peripheral vascular smooth muscles and indirect
effects through release of endogenous histamine.

It reduces pulmonary arterial pressure and vascular resistance.[1]

Structure Activity Relationship

Molecules with 2,6-disubstitutions, which assume an orientation where the phenyl and
imidazoline rings are in different plans are having the highest activity.

Electronic effects have only influence on the actions at H2; action on α-receptors are not
influenced.

Substitutions at 3, 4 or 5 positions of the phenyl ring preclude potent activity at H2-receptor sites
while the α-receptor activity is maintained.

Method of synthesis

Heterecyclation of the ethyl ester of iminophezylacetic acid with the help of ethylenediamine
give tolazoline.

Therapeutic Uses

Reducing PVR

Thrombophlebitis

Thromboangitis obliterans

Spasm

Scleroderma

Raynaud disease

Persistant fetal circulation syndrome

Peripheral vascular diseases

Causalgia

Arteriosclerosis obliterans

Side Effects

Stomach bleeding

Intestinal bleeding

Decreased urine production

Keidney failure

Hypotension

Fall in level of chlorine in blood

Widening of blood vessels

Vomiting

Goose bumps

Nausea

Fast heartbeat

Diarrhea

Dilated pupils

Propranolol

IUPAC nomenclature

(RS)-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol.
Classification

Propranolol is a nonselective ß-adrenergic antagonist.

Mechanism of Action

i. Propranolol blocks ß-adrenergic receptors.

ii. This leads to vasoconstriction, inhibition of angiogenic factors and basic growth factors of
fibroblast, induction of apoptosis of endothelial cells and regulation of RAAS system. [1]

Structure Activity Relationship

Increasing the chain length of the side chain prevents appropriate binding of the required
functional groups to the same receptors side.

Side chain of aryloxypropanolamines can adopt a conformation that places the hydroxyl and
amine groups into approximately the same position in space.

Aryloxypropalonamines permits a close overlap with the arylethanomine side chain.

Aryloxypropanolamines are more potent than aryloxyethanolamines.

Method of synthesis

i. Reaction of 1-naphthol with epichlorohydrin gives 1-chloro-3-(1-naphthyloxy)-2-propanol.

ii. Latter compound is reacted with iso-propylamine to give propranolol.

Therapeutic Uses

Propranolol is used for treatment of:

Tremors

Angina

Hypertension

Heart rhythm disorders

Treatment and prevention of heart attacks

Reducing migraine headaches