Cyclization-activated prodrugs. Basic esters of 5-bromo-2'-deoxyuridine

Some 3'- and 5'-[[(alkylamino)ethyl]glycyl] esters of 5-bromo-2'-deoxyuridine were prepared and evaluated in vitro as progenitors of the parent alcohol. The esters proved to be relatively stable at low pH but released 5-bromo-2'-deoxyuridine cleanly at rates which were pH and str...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1990-09, Vol.33 (9), p.2590-2595
Main Authors: Saari, Walfred S, Schwering, John E, Lyle, Paulette A, Smith, Steven J, Engelhardt, Edward L
Format: Article
Language:English
Subjects:
Bromodeoxyuridine - analogs & derivatives
Chemical Phenomena
Chemistry
Cyclization
Esters
Prodrugs - chemical synthesis
Prodrugs - pharmacokinetics
Structure-Activity Relationship
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Summary:Some 3'- and 5'-[[(alkylamino)ethyl]glycyl] esters of 5-bromo-2'-deoxyuridine were prepared and evaluated in vitro as progenitors of the parent alcohol. The esters proved to be relatively stable at low pH but released 5-bromo-2'-deoxyuridine cleanly at rates which were pH and structure dependent. These basic esters are examples of cyclization-activated prodrugs in which generation of active drug is not linked to enzymatic cleavage but rather results from an intramolecular cyclization-elimination reaction.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00171a038