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

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

Rabeprazole

IUPAC nomenclature

(RS)-2-([4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole.

Classification

  • Proton pump inhibitors

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 359.4  g/mol
2 Physical appearance White to yellowish white solid
3 Melting point 99-100oC
4 Solubility Very soluble in water and methanol; insoluble in ether
5 Octanol/water partition coefficient 0.6
5 Presence of ring Pyridine, benzimidazole
6 Number of chiral centers Not present

 

 

Mechanism of Action

  • Rabeprazole is a prodrug which requires protonation via an acidic environment to get activated form Sulphenamide.
  • Sulphenamide covalently binds with cystien residues via disulfide bridges on the α subunit of H/K ATPaseenzyme 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. 4-nitro-2,3-dimethylpyridine-N-oxide is heated with conc. HCl to get 4-chloro-2,3-dimethylpyridine-N-oxide.

ii. Last is reacted with sodium 3-methoxypropan-1-olate in DMSO to get 4-alkoxy intermediate.

iii. On reaction of intermediate with acetic anhydride, produces O-acetyl intermediate.

iv. On alkaline hydrolysis of the above formed intermediate produces pyridine-2-ylmethanol.

v. The last is chlorinated using thionyl chloride to get a chloro intermediate.

vi. The above formed intermediate is condensed with help of 2-mercaptobenzimidazole in the presence of a base to get 2-((pyridine-2-ylmethyl)thio)-1H-benzo[d]imidazole derivative.

vii. Oxidation of last with meta-chloroperbenzoic acid yields rabeprazole.[2]

Medicinal Uses

Rabeprazole is used for treatment of:

  • Stomach ulcers
  • Active duodenal ulcers
  • Active benign gastric ulcer
  • GERD
  • Erosive esophagitis
  • Zollinger-Errison syndrome
  • pylori eradication 

 

 

Side Effects

Side effects of Rabeprazole are:

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

 

 

MCQs

Q.1 “(RS)-2-([4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole” is the IUPAC nomenclature of which drug?

a) Rabeprazole

b) Nimodipine

c) Promethazine

d) Clemastine

Q.2 Melting point of Rabeprazole is?

a) 100oC

b) 193oC

c) 160 oC

d) 652oC

Q.3 Match the following with correct classifications of the drugs.

i. Rabeprazol A. Proton pump inhibitor
ii. Ranitidine B. Calcium channel blocker
iii. Metformin C. Antidiabetic agent
iv. Nimodipine D. H2-antihistamine

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

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

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

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

Q.4 Mechanism of action of Rabeprazole includes?

I. Inhibition of H+/K+ ATPase pump

II. Antagonistic effects on H2-receptor.

III. Effects on Muscarinic receptors

IV. Reduction in acidity of stomach

a) I, II

b) I, IV

c) I, II, III

d)I,  III

Q.5   Correct sequence for True and False for general structure activity of Heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]Pyridine derivatives acting as acid pump antagonists drugs can be?

  • 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

a) TTFT

b) TFTF

c) TTTT

d) FFTT

Q.6 Type of ring structure present in the structure of rabeprazole is?

a) Benzimidazole

b) Pyrimidine

c) Pyran

d) Phenyl

Q.7 The drug Rabeprazole is mainly used for treatment of?

a) Stomach ulcers

b) GERD

c) Zollinger-Errison syndrome

d) All of the above

 

 

 

For More Standard and Quality Question Bank you can Join Our Test Series Programme for GPAT, NIPER JEE, Pharmacist Recruitment Exam, Drug Inspector Recruitment Exams, PhD Entrance Exam for Pharmacy

Participate in Online FREE  GPAT  TEST: CLICK HERE

  Participate in Online FREE  Pharmacist  TEST: CLICK HERE 

Participate in Online FREE  Drug Inspector  TEST: CLICK HERE 

Participate in CSIR NET JRF Mock Test

Participate GATE Mock Test

 

 

ANSWERS

1-a

2-a

3-a

4-b

5-c

6-a

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

 

Leave a Reply

Your email address will not be published. Required fields are marked *

20 − twelve =

×
PG Diploma in Advance Clinical Research 2020
Apply now

Developed By Connect Globes