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 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.
Saari
W S
WS
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Schwering
J E
JE
Lyle
P A
PA
Smith
S J
SJ
Engelhardt
E L
EL
D001973:Bromodeoxyuridine / Q000031:analogs & derivatives*; D055598:Chemical Phenomena; D002621:Chemistry; D003500:Cyclization; D004952:Esters; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
D004952:Esters; D011355:Prodrugs; D001973:Bromodeoxyuridine