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CONTEXT Quinazolines are a common class of nitrogen-containing heterocyclic scaffolds exhibiting a broad spectrum of pharmacological activities. OBJECTIVE In the present study, quinazoline and quinazolin-4-one derivatives were prepared, characterized to evaluate their biological which may pave the way for possible therapeutic applications. MATERIALS & METHODS A new derivative of quinazoline and quinazolin-4-one derivatives was prepared and tested for antiulcerogenic, anti-inflammatory and hepatoprotective activity. RESULTS The synthesized compounds were characterized by elemental analysis and spectral data. Also, the median lethal doses (LD50s) of compounds 1-3 in rats were 1125, 835 and 1785 mg/kg b.w., respectively. IC50 values of compounds (1-3) as measured by ABTS+ radical method was 0.8, 0.92 and 0.08 mg/mL, respectively. Antiulcerogenic activities at dose 1/20 LD50 in albino rats were 47.94, 24.60 and 56.45%, respectively. Anti-inflammatory effect at dose 1/20 LD50 of compounds (1-3) induced edema model after 120 min. The prepared compounds possess hepato gastric mucosa protective activity against ibuprofen-induced ulceration and LPS-induced liver toxicity, respectively in rats via normalization of oxidative stress biomarkers and inflammatory mediators were inhibited in peritoneal macrophage cells at concentration of 100 µg/L. Molecular docking suggested that the most active compounds 1 and 2 can be positioned within the active sites of COX-2 at Arg121 & Tyr356 similar to ibuprofen (Arg-120, Glu-524, and Tyr-355). The compound 3-COX-2 complex generated by docking revealed intricate interactions with a COX-2 channel. CONCLUSION These findings suggest that compounds 1-3 exhibited good antioxidant, antiulcer, anti-inflammatory activity and safe on liver enzymes in rats.