| |
[摘要]：9-(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and its cyclic from were selected for further evaluation as potential drug candidates against poxvirus infections. To increase bioavailability of these compounds, synthesis of their structurally diverse ester prodrugs was carried Out: alkoxyalkyl (hexadecyloxypropyl. octadecyloxyethyl. hexadecyloxyethyl). pivaloyloxymethyl (POM 2,2.2-trifluoroethyl, butylsalicylyl. and prodrugs based on peptidomimetics. Most I PM PI)A P prodrugs were synthesized in the Form of monoesters is well as the corresponding cyclic phosphonate esters. The activity was evaluated not only against vaccinia virus hut also against different herpes viruses. The most potent and active prodrugs against vaceinia virus were the alkoxyalkyl ester derivatives of HPMDAP. with 50% effective concentrations 400-600-fold lower than those of the parent compound. Prodrugs based on peptidomimetics, the 2,2,2-trifluoroethyl. the POM, and the butylsalicylyl derivatives, were able to inhibit vaccinia virus replication at 50% effective concentrations that were equivalent or similar to 10-fold lower than those observed for the parent compounds. |
|
