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

Zanamivir

IUPAC nomenclature

(2R,3R,4S)-4-guanidino-3-(prop-1-en-2-ylamino)-2-((1R,2R)-1,2,3-trihydroxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid.

Classification

Zanamivir is a Neuraminidase inhibitor analogue.

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 332.31  g/mol
2 Physical appearance White to off-white powder
3 Melting point 256°C
4 Solubility 18 g/L in water
5 Octanol/water partition coefficient -3
6 Presence of ring Pyrane
7 Number of chiral centers 5
 

 

Mechanism of Action

  • Drug binds with neuraminidase protein and inhibits it which unable the virus to escape from the host cell and infect other cells.

Structure Activity Relationship

  • Zanamivir sulfonate exhibit stronger binding to avian influenza neuraminidase H5N1 than their carboxylate and phosphate analogues.
  • Alkoxyl ester derivatives have better bioavailability when administered orally.
  • C-4 modified drug having different alkyl chains are most efficient.
  • The C-4 derivatization of drug with thiocarbamates, α-amino acids or cyclic secondary amines led to decreased inhibitory activities.
  • L-aspargine bearing analogues show best results. [1]

 

Method of synthesis

i. Neu5Ac is converted into ethyl ester (1).

ii. Treatment with acetic anhydride in acetic acid containing a catalytic amount of sulfuric acid to give (2).

iii. Ring opening reaction with trimethylsilyl azide.

iv. (4) undergoes hydrogenation and converts into guanidine derivative (6) by treatment with (5) using HgCl2 as the promoter

v. Zanamivir is isolated after saponification and removal of tert-butoxycarbonyl using TFA. [1]

 

Therapeutic Uses

Zanamivir is used for:

  • Treatment of symptoms of influenza virus.
  • Swine flu treatment

 

Side Effects

Side effects of Zanamivir are:

  • Dizziness
  • Increased cough
  • Breathing problems 

                                                        MCQ

Q.1 Match the following with correct SAR of the drug zanamivir-

i. C-4 modified drug having different alkyl chains A. decreased inhibitory effects
ii. Alkoxy ester derivatives B. Better bioavailability when given orally.
iii. Sulfonates C. stronger binding with influenza
iv.C-4 derivaization with thiocarbamates D. most efficient

 a) i-A, ii-C, iii-B, iv-D

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

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

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

Q.2 Correct sequence for the True/False for correct IUPAC names of the drug can be?

  • Zanamivir: 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide.
  • Favipiravir: 7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepine-2-thione
  • Lopinavir: 22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
  • Benztropin: (RS)-2-[{4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino]ethanol

a) TFTF

b) TTFF

c) FFFF

d) TFTT

Q.3 Physical appearance of zanamivir drug is?

a) White to off white powder

b) Pale yellow powder

c) Yellow liquid

d) Transparent oil

Q.4 Zanamivir binds with?

a) Neuraminidase protein

b) α-receptors

c) Nicotinic receptor

d) None of the above

Q.5 Which amongst the following is a therapeutic use of drug Zanamivir?

a) Treatment of hepatitis C

b) Treatment of anxiety

c) Treatment of influenza

d) Treatment of HIV

Q.6 Which of the following drug and their classification are correct?

I. Acyclovir: Nonbezodiazepine sedative-hypnotic

II. Cidofivir: Synthetic guanosin neucleoside

III. Boceprivir: Non nucleoside analogue

IV. Amrenavir: HIV protease inhibitor

a) II, III

b) III, I

c) II, IV

d) III, IV 

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

a) -3

b) 2

c) 1.85

d) -2.0

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ANSWERS

1-d

2-b

3-a

4-a

5-c

6-d

7-a

 

REFERENCES

[1] Laborda P, Wang SY, Voglmeir J. Influenza neuraminidase inhibitors: synthetic approaches, derivatives and biological activity. Molecules. 2016 Nov;21(11):1513.

 

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