Monoval-LdC: Efficient Prodrug of 2′-Deoxy-β-L-cytidine (L-dC), A Potent and Selective Anti-HBV Agent

Abstract

In order to improve the oral bioavailability of LdC, valinyl esters were prepared as prodrugs. We report here the syntheses of the 3′-mono-, 5′-mono, and 3′,5′-di-O-valinyl esters of LdC. The comparison of their ease of synthesis, their physicochemical properties, as well as their pharmacokinetic parameters in cynomologus monkeys has revealed 3′-mono-O-valinyl derivative as the most promising of the studied prodrugs. This compound is being developed as a new anti-HBV agent.