Synthesis and anti-HIV evaluation of D4T and D4T 5'-monophosphate prodrugs

Synthesis and anti-HIV evaluation of D4T and D4T 5'-monophosphate prodrugs Aryl Phosphoramidate Derivatives of d4T Have Improved Anti-HIV Efficacy in Tissue Culture and May Act by the Generation of a Novel Intracellular Metabolite Uncharged AZT and D4T Derivatives of Phosphonoformic and Phosphonoacetic Acids as Anti-HIV Pronucleosides 1-(2,3-Dideoxy-.beta.-D-glycero-pent-2-enofuranosyl)thymine. A highly potent and selective anti-HIV agent Simple mono-derivatisation of the aryl moiety of D4A and DDA-based phosphoramidate prodrugs significantly enhances their anti-HIV potency in cell culture Diaryl phosphate derivatives act as pro-drugs of AZT with reduced cytotoxicity compared to the parent nucleoside Mononucleoside phosphorodithiolates as mononucleotide prodrugs Phosphoramidate derivatives of d4T with improved anti-HIV efficacy retain full activity in thymidine kinase-deficient cells Phosphoramidate derivatives of 2′,3′-didehydro-2′,3′-dideoxyadenosine [d4A] have markedly improved anti-HIV potency and selectivity Aryl phosphate derivates of AZT inhibit HIV replication in cells where the nucleoside is poorly active