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

Abstract
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.

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