Synthesis and Evaluation of Some Novel Phosphoramidate Derivatives of 3′-Azido-3′-Deoxythymidine (AZT) as Anti-HIV Compounds

A series of monophosphate triester derivatives of 3′-azido-3′-deoxythymidine (AZT), designed as membrane-soluble pro-drugs of the nucleotide (AZTMP), have been tested for activity against the human immunodeficiency virus (HIV-1). It has been found that when carboxyl-protected, amino-linked amino acids, and alkyl chains, are asymmetrically substituted on the 5′-phosphate a significant antiviral effect is observed. Moreover, the activity of the compounds is profoundly dependent on the structure of the phosphate moiety, and in particular on the nature of the amino acid.