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

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

Lansoprazole

IUPAC nomenclature

2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]-1H-benzimidazole

Classification

  • Proton pump inhibitors

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 369.4  g/mol
2 Physical appearance White to brownish-white crystalline powder
3 Melting point 178-182oC
4 Solubility Freely soluble in dimethylformamide; insoluble in hexane and water
5 Octanol/water partition coefficient N/A
5 Presence of ring Pyridine. Benzimidazole
6 Number of chiral centers Not present

 

Mechanism of Action

  • Lansoprazole is a prodrug which requires protonation via an acidic environment to get activated.
  • Lansoprazol 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

i. 2,3-dimethyl-4-nitropyridine-1-oxide is reacted with 2,2,2-trifluoroethanol in presence of potassium carbonate to give 2,3-dimethyl-4-(2,2,2-trifluoro-ethoxy)pyridine-1-oxide.

ii. The compound so formed is treated with acetic anhydride in acidic conditions followed by nutrilizing with sodium hydroxide solution to get 2-hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)-pyridine.

iii. Last is treated with thionyl chloride followed by reaction with 2-mercaptobenzimidazole to get 2-[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-ylmethylthio]benzimidazole.

iv. Above formed compound is reacted with m-chloro-perbenzoic acid to get lansoprazole.[2]

Medicinal Uses

Lansoprazole is used for treatment of:

  • Stomach ulcers
  • 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
  • NSAID induced gastric ulcers 

 

Side Effects

Side effects of Lansoprazole are:

  • Abdominal pain
  • Nausea
  • Constipation
  • Headache
  • Low magnesium blood level
  • Irregular heartbeat
  • Muscle spasms
  • Seizures
  • Lupus
  • Diarrhea
  • Blood in stool

  

 

MCQs

Q.1 Correct statements from the following related with the physicochemical properties of drug Lansoprazole are?

I. Molecular weight: 474.9 gm/mol

II. Appearance: Oil

III. Melting Point: 190 oC

IV. Solubility: Isoluble in water

a) I, II, III

b) I, III, IV

c) IV

d) I, II, III, IV

Q.2 Match the following of the drugs with their correct IUPAC names.

i. Lansoprazole A. (RS)-6-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole
ii. Isoxicam B. 4-hydroxy-2-methyl-N-(5-methyl-1,2-oxazol-3-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
iii. Doxylamine C. (RS)-N,N-dimethyl-2-(1-phenyl-1-pyridin-2-yl-ethoxy)-ethanamine
iv. Pentoprazole D. 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]-1H-benzimidazole

 a) i-D, ii-B, iii-C, iv-A

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

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

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

Q.3 Mechanism of action of drug Lansoprazole involves?

I. Protonoation to get activated

II. Inverse agonist for H1 receptor

III. Inhibition of the H+/K+ ATPase pump

a) I, III

b) I, IV

c) I, II, III

d) II, III

Q.4 Correct sequence for True/false for the classification of the drug can be?

  • Lansoprazole: H1-receptor antihistamine drug
  • Chlorprothixene: Sedative-hypnotics
  • Omeprazol: H1-antagonist
  • Desflurane: Corticoids

a) TFTF

b) TTFF

c) TFTT

d) FFFF

Q.5  In Heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]Pyridine derivatives acid-pump antagonists, inhibitory property depends on?

a) Hydrophobic group position

b) GTCIvalue

c) Hydrophobic value

d) All of the above

Q.6 Type of rings present in the structure of Lansoprazole?

I. Pyridine

II. Piperazine

III. Benimidazole

IV. Benzodiazepine

a) I, IV

b) I, II

c) I, III

d) II

Q.7 Side effect of drug Lansoprazole is/are?

a) Nausea

b) Seizures

c) Diarrhea

d) All of the above

 

 

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ANSWERS

1-c

2-a

3-a

4-d

5-d

6-c

7-d

 

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] EP 174 726 (Takeda; appl. 31.7.1985; J-prior. 16.8.1984).stabilized pharmaceutical formulation.

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