Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity

Amino acid ester prodrugs of the thiazolides, introduced to improve pharmacokinetic parameters parent drugs, proved be stable as their salts but were unstable at pH > 5. Although some instability was due simple hydrolysis, we have found that main end products degradation peptides formed by rearrangement. These solids: they maintained significant antiviral activity, and in general, showed improved pharmacokinetics (better solubility reduced clearance) compared thiazolides. We describe preparation evaluation these peptides.