The physiological consequences of COX-2 overexpression in the development of cancer, diabetes and neurodegenerative diseases have made this enzyme a promising therapeutic target. Herein, COX-2 active site was analyzed and new molecules were designed. We identified a highly potent molecule (S)-3a with IC₅₀ value and the selectivity for COX-2 0.6 nM and 1666, respectively. The MTD of (S)-3a was 2000 mg kg⁻¹ and its pharmacokinetic studies in rat showed t_1/2 7.5 h. This compound reversed acetic acid induced analgesia and carragennan induced inflammation by 50% and 25% in rat when used at a dose 10 mg kg⁻¹. Mechanistically, it was found that compound (S)-3a inhibits COX-2. Overall, the combination of physico-chemical and biological experiments facilitated the development of a new lead molecule to anti-inflammatory drug.