We have developed a new idea to synthesize key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effective. Key intermediate (3) and final compounds (4a–n) were synthesized in a higher yield of 95% and 80–88% respectively. Further, final compounds (4a–n) were assessed for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = −6.859 and 4n = −7.077) as compared to control indomethacin (−6.109).State-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.