In Silico Screening, Synthesis And Pharmacological Screening of Quinazolinones Containing Oxazepinone Ring as NMDA Receptor Antagonists for Anticonvulsant Activity: Part -I

Abstract

Background: NMDA receptor specifically NR2B subunit plays a major role in eliptogenisis. Antagonists at NR2B receptor site have importance in design of anticonvulsant agents. Some quinazolinones and oxazepine have inherent drug likeliness for anticonvulsant activity. In this research work in silico biological activity spectrum (BAS), ADME prediction, Log P predictions and docking was carried out. A library of quinazolinones with oxazepinone ring was designed, from this library 3-(6-halo-2-methyl-oxoquinazolin-3-(4H-yl)-2-(substituted phenyl)-2, 3-dihydro-1,3-oxazepine-4,7-dione (AMQ 1-5 ) were prioritized for actual synthesis and pharmacological screening for NMDA receptor antagonistic activity. Method: The prioritized molecules were synthesized and characterized by melting point, IR, 1 H-NMR, TLC and elemental analysis. AOT was performed to determine LD 50 of prioritized molecules, further compounds were evaluated for their in vivo antagonistic activity on NMDA induced convulsions in mice. Result: Prioritized molecules AMQ 1-5 exhibited potent antagonistic activity on NMDA receptor. Conclusion: The compound of series AMQ 1 and AMQ 5 were showed significant activity compared to standard memantine used in the assay.

In silico Design, Synthesis and Pharmacological screening of Quinazolinones as NMDA receptor antagonists for Anticonvulsant activity: Part II

“…General procedure for synthesis of the target compound (SMMB [1][2][3] ) All chemicals were procured from, SD Fine, Spectrochem, Sigma Aldrich and Merck.…”

“…SHIMADZU Affinity-I spectrophotometer was for recording the IR spectrum. General synthesis scheme of the target compound [7][8][9][10][11] (SMMB [1][2][3] ) To a solution of barbituric acid (0.01 mol)/ thiobarbituric acid (0.01 mol) in methanol as solvent, formaldehyde (0.02 mol) and 3-amino-2-methylquinazolin-4(3H)-one (0.02 mol) were added drop wise. The reaction mixture was refluxed on a steam bath for 4 hr.…”

“…In part-I of this series of research papers we published the data of some quinazolinones attached with oxazepinone rings as NMDA receptor antagonists for anti-convulsant activity which can serve as anti-convulsant "leads" with activity of 70% as compared with memantine, apotent anticonvulsant agent. In continuation of our work on discovery of potent NMDA receptor antagonists from quinazolinone series, [1][2][3] we here report the quinazolinones with thiobarbituric acid and barbituric acid moieties as potent NMDA receptor antagonists for anticonvulsant activity. This research work consists of in silico screening, synthesis, characterization and pharmacological screening of some Quinazolinones containing barbituric acid and thiobarbituric acid moieties as NMDA receptor antagonists for anticonvulsant activity.…”

“…This research work consists of in silico screening, synthesis, characterization and pharmacological screening of some Quinazolinones containing barbituric acid and thiobarbituric acid moieties as NMDA receptor antagonists for anticonvulsant activity. With a series of molecules as described (series SMMB [1][2][3] were in silico prioritized by molecular docking to obtain antagonism scores using Vlife sciences MDS 4.3 drug design software. Pre ADMET software was used for prioritization of molecules based upon ADME properties.…”

Synthesis, Characterization and DFT Study of 4,4′-Oxydianiline Imines as Precursors of Tetrahalo-1,3-oxazepine-1,5-dione

“…Oxazepine was synthesized by cycloaddition reaction which is a type of pericyclic reaction [2].The importance of 1,3-oxazepine is ascribed to their applications as anticonvulsant [3][4][5][6][7], antidepressant [8], skeletal muscle relaxants [9], neuroleptic [10], antitumor agent [11], antibacterial [12], anti-corrosion [13], anti-anxiety [14]. Many researchers were reported the synthesis of 1,3-oxazepine by either maleic anhydride or phthalic anhydride [15][16][17].The novelty of the present paper is the synthesis two core 1,3-oxazepine in same molecule by using substitute phthalic anhydrides and DFT Study of 4,4′-oxydianiline Imines as precursors of tetrahalo-1,3-oxazepine to calculate the energies of the HOMO and LUMO orbitals used to predict some physical properties of Schiff bases M1-M4, such as hardness, electron affinity A, Ionization potential I, absolute electronegativity μ, absolute hardness η, and electrophilicity w, stability and aromaticity.…”