Kinetic and Stability Study of an Investigative Antirhinovirus Compound

A hydrolytic acid and base catalyzed ring opening reaction has been demonstrated for a 1,2,4-oxadiazole antiviral compound (WIN 63843) resulting mainly in an amidoxime product. Decomposition products and related impurities were detected using a gradient HPLC method. The hydrolysis reaction was first-order for 35% ethanol/buffer solutions in a 50°C chamber or a light cabinet (1000 ft-candles), the greatest stability being between pH 4 and 6. Furthermore, increasing ethanol concentrations resulted in a great decrease in reaction rates. Therefore, for oral or aerosol solution formulations, light protection, pH control between 4 and 6 and the highest permissible ethanol concentrations would be advantageous. This study has shown that the highly electronegative trifluoromethyl group at the 5 position increases the lability of a 1,2,3-oxdiazole compound.