In Silica Screening, Synthesis and Pharmacological Screening of Quinazolinones Containing Oxazepinone Ring as NMDA Receptor Antagonists for Anticonvulsant Activity: Part –I

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, ¹H-NMR, TLC and elemental analysis. AOT was performed to determine LD₅₀ 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 AMQ₁ and AMQ₅ were showed significant activity compared to standard memantine used in the assay.

Key words: In silico, NMDA receptors, Anticonvulsant activity, Quinazolinone, Oxazepinone, Docking.