Synthesis, Characterization and Preliminary Pharmacological Evaluation of New Naproxen Containing 1,3,4-thiadiazole-2-thiol Derivatives

Based on naproxen, in this study, a new series of 1,3,4-thiadiazol-2-thiol derivatives was prepared through the esterification of the carbonyl group (of naproxen) using thionyl chloride as an auxiliary agent with methanol, and then naproxen hydrazide was made, to be obtained using (CS2) and a basic media convert it to the potassium salt of dithiocarbazate. It was oxidized with concentrated sulfuric acid to a compound containing the thiol thiadiazole ring, and finally, through an alkylation reaction, the final compounds were produced (Gh1, Gh2, Gh3, Gh4). These compounds were characterized using infrared spectroscopy and proton nuclear magnetic resonance. Then, the anti-inflammatory effectiveness was evaluated in vivo by inducing acute inflammation in laboratory rats with egg whites. The compounds were successfully synthesized with a percentage yield approaching 70%, and it was discovered that they are effective in reducing the thickness of the paw edema of the tested rats and have an anti-inflammatory influence similar to the effect of the reference substance (naproxen) some compounds were more effective than naproxen at some trial times, as or compound (Gh1) at time (T7) after (5) hours of practical experience.