Ibuprofen and 1,3,4 Oxadiazole Based Anti Inflammatory Agents: Synthetic Advances, Bioavailability Enhancement and Emerging Hybrid Derivatives-A Review

Abstract Non‑steroidal anti‑inflammatory drugs (NSAIDs) remain the cornerstone of therapy for pain, inflammation, and fever, despite their well‑recognized gastrointestinal and cardiovascular adverse effects. Ibuprofen, one of the most widely used NSAIDs worldwide, continues to attract significant scientific interest not only because of its clinical relevance but also due to ongoing challenges related to its synthesis, stereo selectivity, and limited aqueous solubility. In parallel, heterocyclic scaffolds such as 1,3,4‑oxadiazoles have emerged as privileged structures in medicinal chemistry, exhibiting diverse pharmacological properties including anti‑inflammatory, antioxidant, and anticancer activities. This review provides a comprehensive and critical overview of recent advances in ibuprofen research, integrating three major aspects: (i) progress in classical and modern synthetic strategies for ibuprofen, with emphasis on greener, shorter, and continuous‑flow methodologies; (ii) pharmaceutical and technological approaches developed to enhance the solubility and oral bioavailability of ibuprofen; and (iii) the rational design, synthesis, and biological evaluation of ibuprofen‑ and NSAID‑inspired 1,3,4‑oxadiazole derivatives as potential next‑generation anti‑inflammatory agents. Particular attention is given to structure–activity relationships, cyclooxygenase (COX‑1/COX‑2) selectivity, molecular docking insights, and in vivo anti‑inflammatory outcomes reported in recent literature. By correlating synthetic chemistry, formulation science, and biological performance, this review highlights current trends and future opportunities for the development of safer and more effective anti‑inflammatory therapies based on ibuprofen and oxadiazole hybrid frameworks. Key words: Ibuprofen, oxadiazole, Anti‑inflammatory