Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372957 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
Abstract
We report the synthesis and biological evaluation of Ala–(Val–)l-Ser–CO2R 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 EC50 value against human cytomegalovirus comparable to 1. Neither 6 nor 7 exhibited toxicity up to 100 μM in KB or HFF cells.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Larryn W. Peterson, Jae-Seung Kim, Paul Kijek, Stefanie Mitchell, John Hilfinger, Julie Breitenbach, Kathy Borysko, John C. Drach, Boris A. Kashemirov, Charles E. McKenna,