In the present study,synthetic chalcones,flavanones and Schiff bases were prepared starting from paraceamol,and evaluated their anticipated anti-inflammatory activity.Chalcones were synthesized by reacting 3-acetyl-4-hydroxy acetanilide and aromatic aldehydes in alcoholic potassium hydroxide(KOH) solution under Claisen-Schmidt condensation conditions.The chalcones were cyclized in the presence of piperidine in isoamyl alcohol to obtain flavonone derivatives.Schiff bases were synthesized by condensing 3-acetyl-4-hydroxy anilines with aromatic aldehydes in the presence of HCl.These Schiff bases were further reacted with other aromatic aldehydes in alcoholic KOH solution.PASS cheminformatics software was used to predict the anti-inflammatory activity of synthesized compounds.PASS software predicted that chalcone-based Schiff bases 6a–d contained structural features that can exhibit anti-inflammatory activity.All the prepared derivatives of acetaminophen exhibited moderate to excellent in vivo anti-inflammatory activity in carrageenan-induced edema in rat paw.All the Schiff bases coupled chalcones showed good anti-inflammatory activity compared with the reference drug,diclofenac.Further evaluation of their therapeutic potential and safety profile is required in the future study. In the present study, synthetic chalcones, flavanones and Schiff bases were prepared starting from paraceamol, and in their supposed anti-inflammatory activity. Chalcones were synthesized by reacting 3-acetyl-4-hydroxy acetanilide and aromatic aldehydes in alcoholic potassium hydroxide (KOH) solution under Claisen-Schmidt condensation conditions. The chalcones were cyclized in the presence of piperidine in isoamyl alcohol to obtain flavonone derivatives. Schiff bases were synthesized by condensing 3-acetyl-4-hydroxy anilines with aromatic aldehydes in the presence of HCl. The Sechiff bases were further reacted with other aromatic aldehydes in alcoholic KOH solution. PASS cheminformatics software used to predict the anti-inflammatory activity of synthesized compounds. PASS software predicted that chalcone-based chiffon 6-d contained structural features that can exhibit anti-inflammatory activity.All the prepared derivatives of acetaminophen exhibited moderate to excellent i n vivo anti-inflammatory activity in carrageenan-induced edema in rat paw. All of the Schiff bases coupled chalcones showed good anti-inflammatory activity compared with the reference drug, diclofenac. Further evaluation of their therapeutic potential and safety profile is required in the future study .