Design, Synthesis, Characterization and Pharmacological Evaluation of Novel Imidazole-Based Oxazolone Derivatives as Potential Analgesic and Anti-Inflammatory Agents
The study was undertaken to design, synthesize, characterize, and evaluate novel imidazole-based oxazolone derivatives (OXA01–OXA09) possessing two pharmacophoric systems with the goal of identifying new analgesic and anti-inflammatory lead compounds. A systematic research plan was followed that included molecular design, multi-step organic synthesis, purification, analytical characterization, in vivo pharmacology, in vitro cytotoxicity, and molecular docking. Oxazolone derivatives were synthesized via cyclodehydration of benzoylglycine intermediates with various substituted aryl aldehydes in acetic anhydride–sodium acetate under catalytic ZnO. All intermediates and final compounds were purified and structurally confirmed by TLC, melting point analysis, IR, ¹H/¹³C NMR, LC–MS, and elemental analysis, confirming successful formation of the intended oxazolone scaffolds. Acute oral toxicity studies in rodents revealed no mortality or severe toxic symptoms up to 2560 mg/kg, indicating high safety margins and LD₅₀ greater than 2560 mg/kg, classifying the compounds as low-toxicity agents. Most derivatives demonstrated dose- and time-dependent analgesic activity, with OXA03, OXA05, OXA07, and OXA09 showing the strongest effects, in some cases comparable to or exceeding standard drugs (indomethacin and diclofenac). Compounds such as OXA08 and OXA02 also demonstrated moderate yet meaningful activity.