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

Esmolol

IUPAC nomenclature

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

 

 

Classification

Esmolol is a cardioselective ß1-adrenergic antagonist

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 295.37 g/mol
2 Physical appearance Solid
3 Melting point 90°C
4 Solubility Very soluble in hydrochloride salt
5 Octanol/water partition coefficient 1.7
6 Presence of ring Benzene
7 Number of chiral centers 1

 

Mechanism of Action

  • Esmolol competitively binds with ß1-receptors in cardiac tissues and blocks the agonist effect of sympathetic neurotransmitters.
  • It blocks the adrenergic stimulation of cardiac pacemaker potential and produces antiarrhythemic activity. [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. Methyl 3-(4-hydroxyphenyl)propanoate reacts with 2-(chloromethyl)oxirane to give methyl 3-(4-((oxirane-2-yl)methoxy)phenyl)propanoate.

ii. The latter compound is reacted with propan-2-amine to give esmolol.

 

 

Therapeutic Uses

Esmolol is used for treatment of:

  • Heart rhythm disorders
  • Atrial fibrillation
  • Atrial flutter
  • Regulation of blood pressure during surgery

 

 Side Effects

Side effects of esmolol are:

  • Headache
  • Hunger
  • Low blood sugar
  • Irritability
  • Dizziness
  • Nausea
  • Fast heart rate
  • Anxiety
  • Coldness in hands and feet
  • Pain or swelling near the injection site
  • Weak and shallow breathing
  • Wheezing
  • Chest pain
  • Shortness of breath
  • Slow heart beats
  • Lightheadedness

 

MCQs

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

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 esmolol?

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 esmolol from Methyl 3-(4-hydroxyphenyl)propanoate can be?

Reaction with 2-(chloromethyl)oxirane

Reaction with propan-2-amine

III. Reduction with help of Pt-Pd catalyst

 a) III – II – I

b) I – III – II

c) I – II

d) III – I

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

a) Headache

b) Fast heart rate

c) Anxiety

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 ß1-adrenergic antagonist?

a) Dopamine

b) Dobutamine

c) Propranolol

d) Esmolol

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

a) Naphthalene

b) Carbazoline

c) Imidazoline

d) Benzene

 

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ANSWERS

1-b

2-c

3-c

4-d

5-d

6-d

7-d

 

REFERENCES

[1] Benfield P, Sorkin EM. Esmolol. Drugs. 1987 Apr 1;33(4):392-412.

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

 

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