1.
Bioorg Med Chem Lett
; 21(13): 4045-9, 2011 Jul 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-21641218
RESUMEN
We report the synthesis and biological evaluation of Ala-(Val-)l-Ser-CO(2)R prodrugs of 1, where a dipeptide promoiety is conjugated to the P(OH)(2) group of cidofovir (1) via esterification by the Ser side chain hydroxyl group and an ethyl group (4 and 5) or alone (6 and 7). In a murine model, oral administration of 4 or 5 did not significantly increase total cidofovir species in the plasma compared to 1 or 2, but 7 resulted in a 15-fold increase in a rat model and had an in vitro EC(50) value against human cytomegalovirus comparable to 1. Neither 6 nor 7 exhibited toxicity up to 100 µM in KB or HFF cells.