Phosphoramidate conjugates of 3′-azido-3′-deoxythymidine glycerolipid derivatives and amino acid esters: synthesis and anti-HIV activity

We report the synthesis of phosphoramidate conjugates of 3′-azido-3′-deoxythymidine (AZT) glycerolipid derivatives and amino acid esters. For the synthesized compounds, 50% inhibition of the HIV-1 MvP-899 strain in human T lymphoid MT-4 cells is achieved at concentrations of 0.014–0.356 µM. Significantly, compound 3c (which contained ethyl ester of α-alanine) was found to be the most active with EC₅₀ value 0.014 µM. We show that, among these glycerolipid derivatives of AZT, some compounds are less toxic than AZT, and also they possess a similar or higher selectivity index compared to AZT (SI = 11643). [Figure not available: see fulltext.].