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

Abstract

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 are the formal condensation products of anthranilic acid and amides, and 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 [10] and anticonvulsant [11]. 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 developed 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 to now, a great number of various procedures have been proposed for the synthesis of quinazolin-4-ones in the past few years [16]. Using microwave radiation, this reaction could be easily and rapidly performed in very good yields, providing a large quantity 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 reports a drug/ligand or receptor/protein interactions by identifying the suitable active sites in human gamma-aminobutyric acid receptor, the gaba (a)r-beta3 homopentamer human gamma-aminobutyric acid receptor, the gaba (a)r-beta3 homopentamer protein. Results: We are pleased to find that the reaction provided of 3-alkyl/aryl-2-alkyl-quinazolin-4-one gives good yield as well as good quality of product by using MW. All the synthesized compounds were subjected to grid-based molecular docking studies. The results shows that compound 4t have good affinity to the active site residue of human gamma-aminobutyric acid receptor, the gaba (a)r-beta3 homopentamer. Conclusion: The Microwave irradiation for synthesis of the title compounds offers 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 a helpful guide 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.

Prediction of ADME/Tox properties, 2D,3D QSAR and molecular docking approach of 2,3‐disubstituted‐Quinazolin‐4(3H)‐ones using X‐ray crystal structure of Staphylococcus aureus (1T2W) Sortase A

“…[ 32 ] Biological activity and structure of the selected series. Table 1 [ 33‐35 ] is utilized to establish a quantifiable relationship between the compounds physiochemical properties and biological activities through the performance of molecular docking studies and QSAR research against X‐ray crystal structure of Staphylococcus aureus (1T2W) sortase Ausing software package QSARpro and MDS 4.6.…”

Convergent micro-wave assisted synthesis of quinazolinone and its precursor using the bio-sourced solvent pinane

“…Heterocycles are common important building blocks in medicinal chemistry. Quinazolines or quinazolinones are regularly used in the synthesis of bioactive compounds to inhibit epigenetic targets, 1 gamma-aminobutyric acid (GABA) receptors, 2 phosphoinositide 3-kinase (PI3K) signalling 3 and many other biological pathways. 4 Some typical quinazolin(on)es approved for use in clinical applications are presented in Fig.…”

Synthesis of 2-phenyl- and 2-benzyl derivatives of 4(3Н)-quinazolinone with analgesic activity

“…Volume XI, Issue 1, 2023 ВВЕДЕНИЕ Целенаправленный поиск новых высокоэффективных и безопасных субстанций лекарственных препаратов, влияющих на ЦНС, является актуальной задачей фармации [1][2][3]. Эмпирический подход, применяемый при синтетическом получении новых соединений с биологической активностью, недостаточно продуктивен и эффективен [4][5][6][7].…”

“…1 Воронина Т.А., Гузеватых Л.С. Mетодические рекомендации по изучению анальгетической активности лекарственных средств.…”