Synthesis and Medicinal Applications of Fenamic Acid Derivatives

Fenamic acid-derived NSAIDs contain N-phenyl anthranilic acid as a pharmacophore with pKa ∼ 4, which is completely ionized at the physiological pH and is mainly excreted in the urine by hydroxylation or glucuronidation. The acid (-COOH) functionality in fenamic acid provides a template for their fenamate derivatization for the development of analogues based on amidation, esterification, and etherification. Besides the repurposing of fenamates as neuroprotective agents in unmodified form, several of their derivatives have been reported for the management of disease pathogenesis by regulating the responsible pathways. In this review, we discuss the chemical modification of fenamic acid and its medicinal chemistry thereof.