Microwave Assisted Synthesis and Molecular Docking Studies of Some 4-(3H)-quinazolinone Derivatives as Inhibitors of Human Gamma-Aminobutyric Acid Receptor, the GABA (A)R-BETA3 Homopentamer
Authors: Amrutkar Rakesh Devidas , Ranawat Mahendra Sing 
Published: December 2019

Background:

Quinazolines and quinazolinones constitute a major class of biologically
active molecules, both from natural and synthetic sources. The quinazolinone moiety is an important
pharmacophore showing many types of pharmacological activities as shown in recent exhaustive
review on the chemistry of 2-heteroaryl & heteroalkyl-4-quinazolinones4-quinazolinones that
are the formal condensation products of anthranilic acid and amides. They can also be prepared in
this fashion through the Niementowski quinazolinone synthesis, named after it’s discoverer Stefan
Niementowski. Quinazoline and condensed quinazoline exhibit potent central nervous system
(CNS) activities like anti-anxiety, analgesic, anti-inflammatory and anticonvulsant. Quinazolin-4-
ones with 2, 3-disubstitution is reported to possess significant analgesic, anti-inflammatory and
anticonvulsant activities.

Methods:

To expand these views and application profiles, efforts have been made for the synthesis
of a new class of quinazolinone by incorporating different amines into synthesized benzoxazinone
ring by replacing O atom in the ring. Up till now, a great number of various procedures have been
proposed for the synthesis of quinazolin-4-ones in the past few years. Using microwave radiation,
this reaction could be easily and rapidly performed in very good yields, providing a large number
of various 3-substituted-2- propyl-quinazolin-4-one derivatives which can be employed as useful
bioactive compounds. We report a facile and efficient method for the synthesis of 3-substituted-2-
propyl-quinazolin-4-one by the condensation reaction of anthranilic acid or halogen substituted anthranilic
acid or methyl anthranilate, butanoic anhydride with various amines. We also report a
drug/ligand or receptor/protein interactions by identifying the suitable active sites in the human
gamma-aminobutyric acid receptor, the gaba (a)r-beta3 homopentamer human gammaaminobutyric
acid receptor, and the gaba (a)r-beta3 homopentamer protein.

Results:

It was observed in the reaction, 3-alkyl/aryl-2-alkyl-quinazolin-4-one gave good yield as
well as good quality of the product by using MW. All the synthesized compounds were subjected
to grid-based molecular docking studies. The results show that compound 4t has good affinity to
the active site residue of the human gamma-aminobutyric acid receptor, and the gaba (a)r-beta3
homopentamer.

Conclusion:

The Microwave irradiation for the synthesis of the title compounds offers a reduction
in reaction time, operation simplicity, cleaner reaction, easy work-up and improved yields. The
procedure clearly highlights the advantages of green chemistry. The data reported in this article
may be helpful for the medicinal chemists who are working in this area. The protein-ligand interaction
plays a significant role in structural based drug designing. In the present work, we have
docked the ligand, 2, 3-disubstituted quinazolinone with the proteins that are used as the target for
GABA-A receptor.