15414-60-5Relevant academic research and scientific papers
Modified 5'-Trityl Nucleosides as Inhibitors of Plasmodium falciparum dUTPase
Ruda, Gian Filippo,Nguyen, Corinne,Ziemkowski, Przemyslaw,Felczak, Krzysztof,Kasinathan, Ganasan,Musso-Buendia, Alexander,Sund, Christian,Zhou, Xiao Xiong,Kaiser, Marcel,Ruiz-Perez, Luis M.,Brun, Reto,Kulikowski, Tadeusz,Johansson, Nils Gunnar,Gonzalez-Pacanowska, Dolores,Gilbert, Ian H.
experimental part, p. 309 - 320 (2012/01/12)
2'-Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for the treatment of malaria. We previously reported the discovery of 5'-tritylated analogues of deoxyuridine as selective inhibitors of this Plasmodium falciparum enzyme. Herein we report further structure-activity studies; in particular, variations of the 5'-trityl group, the introduction of various substituents at the 3'-position of deoxyuridine, and modifications of the base. Compounds were tested against both the enzyme and the parasite. Variations of the 5'-trityl group and of the 3'-substituent were well tolerated and yielded active compounds. However, there is a clear requirement for the uracil base for activity, because modifications of the uracil ring result in loss of enzyme inhibition and significant decreases in antiplasmodial action. Fewer trips to the dUMP: dUTPase is a potential drug target for the treatment of malaria. We previously reported the discovery of 5'-tritylated analogues of deoxyuridine as selective inhibitors of this P.falciparum enzyme. Herein we report further structure-activity studies of the 5'-trityl group, the introduction of various substituents at the 3'-position of deoxyuridine, and modifications of the base.
Cyclization-Activated Prodrugs. Basic Esters of 5-Bromo-2'-deoxyuridine
Saari, Walfred S.,Schwering, John E.,Lyle, Paulette A.,Smith, Steven J.,Engelhardt, Edward L.
, p. 2590 - 2595 (2007/10/02)
Some 3'- and 5'-glycyl> esters of 5-bromo-2'-deoxyuridine were prepared and evaluated in vitro as progenitors of the parent alcohol.The sters 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.
