Synthesis and Preliminary Pharmacological Evaluation of Esters and Amides Derivatives of Naproxen as Potential Anti-Inflammatory Agents

4-chloro and 4- nitro substituted phenol and aniline incorporated to a carboxylic group of naproxen a well-known non-steroidal anti-inflammatory drug (NSAID) to increase bulkiness were synthesized for evaluation as a potential anti-inflammatory agents with expected COX-2 selectivity. In vivo acute anti-inflammatory activity of these compounds (I-IV) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (2.5 mg/Kg) of naproxen. All tested compounds produced a significant reduction in paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, compounds I and IV might show higher effect comparable to that of naproxen and to that of compounds II & III which may attribute to the higher effect of nitro group than chloride group. The results of this study indicate that esterification and amidation of naproxen with selected pharmacophoric groups enhance or maintain its anti-inflammatory activity. Keywords: anti-inflammatory; naproxen derivatives