2-Nucleos-5'-O-yl-4H-l,3,2-benzodioxaphosphin-2-oxides--A New Concept for Lipophilic, Potential Prodrugs of Biologically Active Nucleoside Monophosphates

摘要

Nuclcoside analogues such as 3'-azido-2',3'-dideoxythyniidine (AZT). 2',3'-dideoxy-2',3'-didehydrothymidine (d4T). 2',3'-dideoxyinosine (ddI). and 2',3'-dideoxycytidme (ddC't are used in antiviral chertiotherapy against AIDS. One of the major problemsin the use of this type of compounds is the imracellular bioavailahility of their 5'-phosphorylated derivatives. One concept to overcome this limitation is the imracellular delivery of the 5'-monophosphates from prodrugs ("kinase-bypass"). In view of the high antiviral activity of nucleoside analogues, the development of nucleotide prodrugs is a challenging goal.