PROPRANOLOL Synthesis, SAR, MCQ,Structure,Chemical Properties and Therapeutic Uses

Propranolol

IUPAC nomenclature

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

Classification

Propranolol is a nonselective ß-adrenergic antagonist.

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 259.34 g/mol
2 Physical appearance Present in solid form.
3 Melting point 96°C
4 Solubility 61.7 mg/L
5 Octanol/water partition coefficient 3.48
6 Presence of ring Naphthalene
7 Number of chiral centers 1

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. [2]

 

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. [3]

Therapeutic Uses

Propranolol is used for treatment of:

  • Tremors
  • Angina
  • Hypertension
  • Heart rhythm disorders
  • Treatment and prevention of heart attacks
  • Reducing migraine headaches

 

Side Effects

Side effects of propranolol are:

  • Uneven or slow heartbeats
  • Lightheadedness
  • Wheezing
  • Trouble in breathing
  • Shortness of breath
  • Weakness
  • Vision problems
  • Coldness of hands and feet
  • Depression
  • Confusion
  • Hallucinations
  • Nausea
  • Stomach pain
  • Itching
  • Tiredness
  • Loss of appetite
  • Dark urine
  • Jaundice
  • Low blood sugar
  • Fever
  • Sore throat
  • Swelling of face and tongue
  • Eyes burning
  • Skin pain
  • Vomiting
  • Diarrhea
  • Constipation
  • Stomach cramp
  • Impotency
  • Decreased sex drive
  • Insomia

 MCQs

Q.1 What can be the correct IUPAC nomenclature of Propranolol?

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

b) methyl (RS)-3-{4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}propanoate

c) (RS)-1-{4-[(2-Isopropoxyethoxy)methyl]phenoxy}-3-(isopropylamino)propan-2-ol

d) (RS)-1-{4-[(2-Isopropoxyethoxy)methyl]phenoxybenzamide

Q.2 Which amongst the following statements is/are incorrect related to the SAR of Propranolol?

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

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

III. Aryloxypropalonamines permits a close overlap with the arylethanomine side chain.

a) I, III

b) II, III

c) I, II, III

d) I, II

Q.3 The correct order for the synthesis of drug propranolol from 1-naphthol can be?

I. Reaction with epichlorohydrin

II. Reaction with isopropylamine

III. Reduction

 a) III – II – I

b) I – III – II

c) I – II

d) III – I

Q.4 Side effects of drug propranolol is/are?

a) Uneven heartbeats

b) Trouble breathing

c) Vision problems

d) All of the above

Q.5 Match the following drugs with their correct molecular weights-

i. Propranolol A. 295.37 gm/mol
ii. Esmolol B. 309.4 gm/mol
iii. Bisoprolol C. 325.4 gm/mol
iv. Metipranolol D. 259.34 gm/mol

 a) i-B, ii-A, iii-D, iv-C

b) i-B, ii-A, iii-C, iv-D

c) i-B, ii-C, iii-A, iv-D

d) i-D, ii-A, iii-C, iv-B

Q.6 An example of drug from class Nonselective ß-adrenergic antagonist?

a) Dopamine

b) Dobutamine

c) Propranolol

d) Metaraminol

Q.7 The type of ring system found in Propranolol?

a) Naphthalene

b) Carbazoline

c) Imidazoline

d) No ring is present

 

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ANSWERS

1-a

2-c

3-c

4-d

5-d

6-c

7-a

REFERENCES

[1] Wilson AG, Brooke OG, Lloyd HJ, Robinson BF. Mechanism of action of βadrenergic receptor blocking agents in angina pectoris: Comparison of action of propranolol with dexpropranolol and practolol. Br Med J. 1969 Nov 15;4(5680):399-401.

[2] Lemke TL, Williams DA, Foye WO. Principles of medicinal chemistry. Williams & Wilkins; 2017, 356.

[3] Vardanyan R, Hruby V. Synthesis of essential drugs. Elsevier; 2006 Mar 10.

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