Synthesis and Evaluation of some newer Hybrids of Diclofenac Acid and 1,3,4-Oxadiazole: Reduction of Ulceration with Anti-Inflammatory Activity

Diclofenac sodium, an aryl-acetic acid derivative, is one of the most frequently used NSAIDs worldwide, which was first approved in the United States in 1988 and currently over 5 million prescriptions are filled annually. The presence of the free carboxylic acid group in the diclofenac moiety, is mainly responsible for the associated side effects. A number of synthetic approaches have been developed which are associated with the chemical modification of ?COOH moiety with the aim of improving safety profile and in turn therapeutic window of diclofenac. Several studies have been described for the derivatization of the carboxylate function of diclofenac, with less acidic azoles, viz. 1, 3, 4-oxadiazole, etc. and resulted in an increased anti-inflammatory activity with reduced ulcerogenicity. Herein we report the synthesis of some newer derivatives of diclofenac acid by the modification of carboxylate moiety with 1, 3, 4-oxadiazole and their effect on anti-inflammatory activity and ulcerogenicity.