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

Amprenavir

IUPAC nomenclature

(3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1-phenylbutan-2-yl]carbamate

Classification

Amprenavir is an HIV protease inhibitor.

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 505.6 g/mol
2 Physical appearance Solid
3 Melting point °C
4 Solubility 40 mg/L in water
5 Octanol/water partition coefficient log Kow = 2.2 at 25oC
6 Presence of ring Furan, phenyl
7 Number of chiral centers 3
 

 

Mechanism of Action

i. Inhibition of HIV viral proteinase enzyme by amprenavir.

ii. Noninfectious, immature viral particles are produced.

  

Structure Activity Relationship

  • The receptors are bean shaped having a predominantly hydrophobic pocket in the upper half of the region with distinct ‘V’ shape.
  • The hydrophilic region is present at the periphery having H-bond acceptor rich area which can also accommodate a positive salt bridge in the form of terminal aromatic ring.
  • The bean shape structure of the inhibitor has a prominent H-bond acceptor region lies in the center depression.
  • In the ionic or hydrophilic sites, ligands may form H-bonds with the active site of the receptor.
  • The absolute planarity in the ligand structure is necessary for the pi-pi –interactions with the receptor. [1]

 

 

Method of synthesis

Co-catalyzed stereo    centered hydrolytic kinetic resolution of racemic 2-(1-azido-2-phenylethyl)oxirane as the chirality inducing step. There is also synthesis of (S)-3-hydroxytetrahydrofuran with 98% enantiomeric property.[2]

Therapeutic Uses

  • Amprenavir for the treatment and prevention of HIV infection.

 

Side Effects

Side effects of Amprenavir are:

  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain

 

MCQs

Q.1 What can be the brand name for drug Amprenavir?

a) Agenerase

b) Anethane

c) Xylocaine

d) Tricaine

Q.2 Which amongst the following statements is/are incorrect related to the SAR of amprenavir?

I. The receptors are bean shaped having a predominantly hydrophobic pocket in the upper half of the region with distinct ‘V’ shape.

II. The hydrophilic region is present at the periphery having H-bond acceptor rich area which can also accommodate a positive salt bridge in the form of terminal aromatic ring.

III. The bean shape structure of the inhibitor has a prominent H-bond acceptor region lies in the center depression.

IV. In the iomic or hydrophilic sites, ligands may form H-bonds with the active site of the receptor.

a) I, II

b) II, IV

c) III

d) None

Q.3 Type of ring present in the structure of Amprenavir?

I. Phenyl

II. Cyclopentane

III. Pyrimidine

IV. Furan

a) I, III

b) II, III

c) I, IV

d) II, IV

Q.4 Side effects of drug Amprenavir is/are?

a) Nausea

b) Vomitting

c) Diarrhea

d) All of the above

Q.5 Match the following drugs with their correct molecular weights-

i.  Amprenavir A. 226.27 gm/mol
ii.  Amobarbital B. 294.27 gm/mol
iii. Estazolam C. 505.6 gm/mol
iv. Quazepam D. 386.6 gm/mol

 a) i-C, ii-A, iii-B, iv-D

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

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

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

Q.6 An example of drug from class HIV protease inhibitor is?

a) Cytarabine

b) Methotraxate

c) Amprenavir

d) 5-FU 

Q.7 Number of chiral centers present in the structure of Amprenavir?

a) 0

b) 1

c) 2

d) 3

 

 

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ANSWERS

1-a

2-d

3-c

4-d

5-a

6-c

7-d

 

REFERENCES

[1] Dubey S, Gowtham G. Multidimensional QSAR modeling of amprenavir derivatives as HIV-Protease inhibitors. Open Journal of Medicinal Chemistry. 2011 Sep 28;1(01):1.

[2] Gadakh SK, Reddy RS, Sudalai A. Enantioselective synthesis of HIV protease inhibitor amprenavir via Co-catalyzed HKR of 2-(1-azido-2-phenylethyl) oxirane. Tetrahedron: Asymmetry. 2012 Jun 30;23(11-12):898-903.

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