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

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

Esomeprazole

 

IUPAC nomenclature

(S)-(−)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole

Classification

  • Proton pump inhibitors

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 345.4  g/mol
2 Physical appearance Solid
3 Melting point 155 oC
4 Solubility Very soluble in water
5 Octanol/water partition coefficient 0.6
5 Presence of ring Imidazole, pyridine
6 Number of chiral centers Not present

 

Mechanism of Action

  • Esomeprazole covalently binds with cystien residues via disulfide bridges on the α subunit of H+/K+ ATPase enzyme system.
  • Thereby it inhibits the H+/K+ ATPase pump which in turn inhibits the gastric acid secretion or formation of hydrochloric acid in parietal cells

 

Structure Activity Relationship

General structure activity of Heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]Pyridine derivatives acting as acid pump antagonists can be summarized as:

  • The inhibitory property of drugs depends on hydrophobic group substituted at the left side ortho-position of the phenyl ring.
  • Increase in hydrophobic value increases the activity.
  • Increasing the GTCI value decreases the activity.
  • Small molecule substitutions may participate in hydrophobic interaction as well as steric interactions. [1]

 

Method of synthesis

Large scale asymmetric synthesis of esomeprazole can be done by following method:

i. The suspension of pyrmeprazole in toluene is added to water solution of (S, S)-diethyl tartrate and titanium tetraisopropoide.

ii. N, N-diisopropylehylamine and cumene hydroperoxide are added.

iii. Sodium salt is obtained using sodium hydroxide and acetonitrile.[2]

Medicinal Uses

Esomeprazole is used for treatment of:

  • Active duodenal ulcers
  • To reduce the risk of duodenal ulcers by eradicating Helicobacter
  • Active benign gastric ulcer
  • GERD
  • Erosive esophagitis
  • Zollinger-Errison syndrome
  • Reduce heart burn symptoms

  

 

Side Effects

Side effects of Esomeprazole are:

  • Abdominal pain
  • Headache
  • Low magnesium blood level
  • Irregular heartbeat
  • Muscle spasms
  • Seizures
  • Lupus
  • Diarrhea
  • Blood in stool
  • Vitamin B12 deficiency

 

 

MCQs

Q.1 Match the following with correct SAR of the Heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]Pyridine derivative acid-pump antagonists:

i. Increasing the hydrophobic value A. Increases the activity
ii. Increasing  the GTCI value B. Decreases the activity
  C. Increases the activity
  D. Decreases the activity

 a) i-A, ii-C

b) i-A, ii-D

c) i-B, ii-C

d) i-B, ii-D

Q.2 Correct sequence for the True/False for correct IUPAC names of the drug can be?

  • Esomeprazole: 4-(5H-Dibenzo)-1-methylpiperidine
  • Dacarbazine: 4-(diphenylmethoxy)-N,N-dimethylethanamine
  • Loperamide: 2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
  • Zolpidem: 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1λ6,2-benzothiazine

a) TFFT

b)TFFF

c) TTTT

d) FFFF

Q.3 Molecular weight of Esomeprazole is?

a) 453 gm/mol

b) 432.0 gm/mol

c) 187.4 gm/mol

d) 345.4 gm/mol

Q.4 Esomeprazole acts on which system?

a) Sodium potassium pump

b) The respiratory system

c) H+/K+ ATPase pump

d) All of the above

Q.5 Which amongst the following is not a therapeutic use of drug Esomeprazole?

a) GERD

b) Erosive esophagitis

c) Itching

d) Heart burn symptoms

Q.6 Which of the following drug and their classification are correct?

I. Esomeprazole: Proton pump inhibitor

II. Meprilcaine: Local anesthetics

III. Rabeprazole: Diuretics

III. Quinidine: Anti-arrhythmic drug

a) I, III

b) II, III, IV

c) III, IV

d) I, II, IV

Q.7 Number of chiral carbons present in the structure of Esomeprazole?

a) 0

b) 3

c) 4

d) 5

 

 

 

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ANSWERS

1-b

2-d

3-d

4-c

5-c

6-d

7-a

 

REFERENCES

[1] Agarwal N, Bajpai A, Gupta SP. A quantitative structure-activity relationship and molecular modeling study on a series of heteroaryl-and heterocyclyl-substituted imidazo [1, 2-a] pyridine derivatives acting as acid pump antagonists. Biochemistry Research International. 2013 Jan 1;2013.

[2] Vardanyan R, Hruby V. Synthesis of best-seller drugs. Academic press; 2016 Jan 7.

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