Synthesis, Physicochemical and Pharmacokinetic Studies of Potential Prodrugs of β-L-2′-Deoxycytidine, a Selective and Specific Anti-HBV Agent

• Published in: Antiviral chemistry & chemotherapy 2004-10, Vol.15 (5), p.269-279
• Main Authors: Pierra, Claire, Benzaria, Samira, Dukhan, David, Loi, Anna Giulia, La Colla, Paolo, Bridges, Edward, Mao, John, Standring, David, Sommadossi, Jean-Pierre, Gosselin, Gilles
• Format: Article
• Language: English
• Subjects: Acylation; Administration, Oral; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Bioavailability; Biological and medical sciences; Biological Availability; Deoxycytidine - analogs & derivatives; Deoxycytidine - chemical synthesis; Deoxycytidine - pharmacokinetics; Deoxycytidine - pharmacology; Haplorhini; Hepatitis B; Hepatitis B virus - drug effects; Hepatitis B virus - metabolism; Medical sciences; Microbial Sensitivity Tests; Pharmacokinetics; Pharmacology. Drug treatments; Prodrugs; Prodrugs - chemical synthesis; Prodrugs - pharmacokinetics; Prodrugs - pharmacology; Solubility
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/095632020401500506

β-L-2′-Deoxycytidine (β-L-dC) is a potent, selective and specific anti-hepatitis B virus (HBV) agent. To improve its oral bioavailability, several derivatives involving sugar or base acylation, as well as N4-derivatization with an N,N-(dimethyl-amino)methylene function, were synthesized. The physicochemical characteristics (including chemical stabilities, solubilities and distribution coefficient values) and pharmacokinetics of these compounds were determined and compared with those of the parent drug, β-L-dC. Presented in part at the 14th International Conference on Antiviral Research, Seattle, Washington, USA, 8–13 April 2001. Antiviral Reseach 2001; 50:A79.