Saari W S, Schwering J E, Lyle P A, Smith S J, Engelhardt E L
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
J Med Chem. 1990 Sep;33(9):2590-5. doi: 10.1021/jm00171a038.
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.
制备了5-溴-2'-脱氧尿苷的一些3'-和5'-[[(烷基氨基)乙基]甘氨酰]酯，并在体外作为母体醇的前体进行了评估。这些酯在低pH值下相对稳定，但能以依赖于pH值和结构的速率干净地释放出5-溴-2'-脱氧尿苷。这些碱性酯是环化激活前药的例子，其中活性药物的产生不是与酶促裂解相关，而是由分子内环化消除反应导致的。
