Monoval-LdC: efficient prodrug of 2'-deoxy-beta-L-cytidine (L-dC), a potent and selective anti-HBV agent.
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.
Benzaria
S
S
Laboratoire Coopératif Idenix-CNRS-Université Montpellier II, CC 008, Montpellier, France.
Pierra
C
C
Bardiot
D
D
Cretton-Scott
E
E
Bridges
E G
EG
Zhou
X J
XJ
Standring
D
D
Gosselin
G
G
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008252:Macaca fascicularis; D008968:Molecular Conformation; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D000998:Antiviral Agents; D011355:Prodrugs; C479246:monoval-2'-deoxy-beta-L-cytidine; D003841:Deoxycytidine