Omeprazole

IUPAC nomenclature

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

Classification

• Proton pump inhibitors

Physiochemical Properties

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-

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