Synthesis, physicochemical and pharmacokinetic studies of potential prodrugs of beta-L-2'-deoxycytidine, a selective and specific anti-HBV agent.
beta-L-2'-Deoxycytidine (beta-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 N4-derivatization with an N,N-(dimethylamino)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, beta-L-dC.
Pierra
Claire
C
Laboratoire Coopératif Idenix-CNRS-Université Montpellier II, Montpellier, France.
Benzaria
Samira
S
Dukhan
David
D
Loi
Anna Giulia
AG
La Colla
Paolo
P
Bridges
Edward
E
Mao
John
J
Standring
David
D
Sommadossi
Jean-Pierre
JP
Gosselin
Gilles
G
D000215:Acylation; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000882:Haplorhini; D006515:Hepatitis B virus / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility
D000998:Antiviral Agents; D011355:Prodrugs; C479246:monoval-2'-deoxy-beta-L-cytidine; D003841:Deoxycytidine