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

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

Omeprazole

IUPAC nomenclature

5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-benzimidazole

Classification

  • Proton pump inhibitors

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 345.4  g/mol
2 Physical appearance White to off-white crystalline powder
3 Melting point 155 oC
4 Solubility Very slightly soluble in water; freely soluble in ethanol; slightly soluble in acetone
5 Octanol/water partition coefficient 2.23
5 Presence of ring Imidazole, pyridine
6 Number of chiral centers Not present

 

 

Mechanism of Action

  • Omeprazole 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 acidsecretion 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

i. 2,3,5-trimethyl-pyridineN-oxide is reacted with HNO2/sulfuric acid followed by NaOH in ethanol to get 4-methoxy-2,3,5-trimethylpyridine N-oxide.

ii. The last is reacted with acetic anhydride to get 4-methoxy-3,5-dimethyl-2-pyridinemethanol acetate

iii. The above formed compound is reacted with sodium hydroxide to get 2-(hydroxymethyl)-3,5-dimethyl-4-methoxy-pyridine.

iv. On reaction of the last with thionyl chloride produces 2-(chloromethyl)-3,5-dimethyl-4-methoxy-pyridine.

v. The last is reacted with 5-methoxy2-mercaptobenzimidazole which is synthesized by reaction of 4-methoxy-o-henylenedimine and potassium ethylxanthogenate, in presence of NaOH, followed by reaction with 3-chloroperbenoic acid to get omeprazole. [2]

Medicinal Uses

Omeprazole 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
  • Pathologic hypersecretory conditions
  • Heart burn 

 

Side Effects

Side effects of Omeprazole are:

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

  

 

MCQs

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

a) 5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-benzimidazole

b) (R)-(+)-2-([3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole

c) (RS)-1-[(4-chlorophenyl)- phenyl-methyl]-4- [(4-tert-butylphenyl) methyl] piperazine

d) (R)-(+)-2-([3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl)-imidazole

Q.2 Which amongst the following statements is/are incorrect related to the General structure activity of Heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]Pyridine derivatives acting as acid pump antagonists?

I. The inhibitory property of drugs depends on hydrophobic group substituted at the left side ortho-position of the phenyl ring.

II. Increase in hydrophobic value decreases the activity.

III. Increasing the GTCI value increases the activity.

a) I

b) II, III

c) I, III

d) I, II, III

Q.3 Types of rings present in the structure of omeprazole?

I. Imidazole

II. Pyridine

III. Pyrolle

IV. Phenyl

a) I, II

b) I, IV

c) II, IV

d) II, III

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

a) Low magnesium blood level

b) Seizures

c) Lupus

d) All of the above

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

i. Omeprazole A. 426.6 gm/mol
ii. Carbinoxamine B. 266.4gm/mol
iii. Oxatomide C. 345.4 gm/mol
iv. Cyclizine D. 290.79 gm/mol

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

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

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

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

Q.6 An example of drug from class proton pump inhibitor?

a) Omeprazol

b) Sotalol

c) Glycopyrrolate

d) All of the above 

Q.7 Octanol/water partition coefficient of Omeprazole is?

a) 2.23

b) 3.2

c) 4.8

d) 7.1

 

 

 

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ANSWERS

1-a

2-b

3-a

4-d

5-c

6-a

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 essential drugs. Elsevier; 2006 Mar 10.

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