3′-Azido-3′-Deoxy-5′-O-Isonicotinoylthymidine: A Novel Antiretroviral Analog of Zidovudine. III. Solubility Studies

Abstract

The pH-solubility behavior and solubility of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (AZT-Iso), an antiretroviral derivative of zidovudine with important biological activity, was studied in water, ethanol, ethanol: water, and n-octanol. The N-pyridine pKa value was determined from its pH-solubility profile, which was in accordance with that of the experimental value of methyl isonicotinate. Also, the ethanol cosolvency in ethanol:water mixtures at 25 degrees C was studied, and log-linear and nonlinear solubilization models were applied to the experimental solubility AZT-Iso data, which allowed us to predict its solubility in those solvent mixtures at a determined content of cosolvent.