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

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

Eszopiclone

IUPAC nomenclature

(S)-(+)-6-(5-Chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl-4-methyl-1-piperazinecarboxylate

 

Classification

Eszopiclone is a nonbenzodiazepine sedative-hypnotic.

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 388.8 g/mol
2 Physical appearance White to light yellow crystalline solid
3 Melting point 202-203°C
4 Octanol/water partition coefficient 0.81
5 Solubility Soluble in water
6 Presence of ring Pyrrolopyrazine, piperidine, benzene
7 Number of chiral centers 1
 

 

Mechanism of Action

The drug binds with GABAA receptors at the site near the diazepine site. This increases the GABAA channel currents significantly, which leads to CNS depression.

Structure Activity Relationship

  • Eszopiclone is having 50 folds higher affinity for GABAA receptors than the (R) enantiomer.
  • Racemic mixture has a shorter half-life.
  • Enantiomeric separation of the (S) –enantiomers decreases the side effects such as residual sedative effects. [1]

Method of synthesis

i. Reduction of 6-(5-chlorine-2-pyridyl)-5,6-dioxo-6,7-dihydro-5H-pyrrol(3,4-b)pyrazine chiral reagent to obtain 6-(5-chlorine-2-pyridyl)-5(S)-hydroxyl-7-oxo-6,7-dihydro-5H-pyrrol(3,4-b)pyrazine.

ii. Reaction of the (2) with 1-chloroformyl-4-methylpiperazine hydrochloride (2) under the action of organic base to obtain the Eszopiclone [2]

 

Therapeutic Uses

Eszopiclone is used for:

  • Treatment of insomnia

 Side Effects

Side effects of Eszopiclone are:

  • Dizziness
  • Difficulty in coordination
  • Dry mouth
  • Unpleasant taste
  • Hallucinations
  • Mood changes
  • Aggressiveness
  • Suicidal thoughts
  • Anxiety
  • Confusion
  • Depression

 

MCQ

Q.1 Correct statements related to the physicochemical properties of drug Eszopiclone are?

I. Molecular weight: 388.8 gm/mol

II. White to yellow in appearance

III. Octanol/water partition coefficient is 0.81

IV. No chiral carbon atoms are present in structure 

a) I, II

b) I II, III

c) II, IV

d) II, IV

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

i. Flavoxate A. 2-(1-piperidyl)ethyl 3-methyl-4-oxo-2-phenylchromene-8-carboxylate
ii. Eszopiclone B. 7-Chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one
iii. Chlordiazepoxide C. 7-Chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide
iv. Lorazepam D. (S)-(+)-6-(5-Chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl-4-methyl-1-piperazinecarboxylate

 a) i-B, ii-C, iii-A, iv-D

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

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

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

Q.3 Correct steps for the mechanism of action of the drug Eszopiclone?

I. Binding with GABA receptors

II. Increase the Binding of GABA to the GABAA receptors

III. Decreases of the binding of GABA to the GABAA receptors

IV.Enhancement of the GABA mediated chloride influx

a) I – III – IV

b) I – IV – II

c) II – III – IV

d) I – II – IV

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

  • Flavoxate: Nicotinic acetylcholine antagonist
  • Aszopiclone: nonbenzodiazepine sedative-hypnotic
  • Chlordiazepoxide: Muscarinic acetylcholine antagonist
  • Lorazepam: Benzodiazepine sedative hypnotic

a) TTFT

b) FFTT

c) FTFT

d) TFTT

Q.5 Correct order for the steps for synthesis of Eszopiclone from 6-(5-chlorine-2-pyridyl)-5,6-dioxo-6,7-dihydro-5H-pyrrol(3,4-b)pyrazine.

I. Reduction

II. Hydrolysis

III. Reaction with 1-chloroformyl-4-methylpiperazine hydrochloride 

a) II – I – III

b) I – III – II

c) II – III

d) I – III

Q.6 Types of ring structure present in Eszopiclone ?

I. Chromine

II. Benzene

III. Piperidine

IV. Pyrrolopyrazine

a) I, II, III, IV

b) II, IV

c) I, III

d) II, III, IV 

Q.7 Side effect of drug Eszopiclone?

a) Dizziness

b) Confusion

c) Hallucinations

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  Free Online Test for GPAT, Pharmacist,Drug Inspector

ANSWERS

1-b

2-d

3-d

4-c

5-d

6-d

7-d

 

 

REFERENCES

[1] Lemke TL, Zito SW, Roche VF, Williams DA. Essentials of Foye’s principles of medicinal chemistry. Wolters Kluwer; 2017, 473-474.

[2] Mandava VN, Kandala S, Jambula MR, Chinta RR, inventors; Reddy’s Laboratories Ltd, Reddy’s Laboratories Inc, assignee. Eszopiclone process. United States patent US 7,476,737. 2009 Jan 13.

Leave a Reply

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

11 + 20 =

×

Developed By Connect Globes