Aryl H-phosphonates. 19. New anti-HIV pronucleotide phosphoramidate diesters containing amino- and hydroxypyridine auxiliaries

Abstract

We have designed a new type of AZT and ddU phosphoramidate diesters containing various combinations of 2-, 3-, 4-aminopyridine and 2-, 3-, 4-hydroxypyridine moieties attached to the phosphorus center, as potential anti-HIV pronucleotides. Depending on the pK_a values of the aminopyridines and the hydroxypyridines used, alternative synthetic strategies based on H-phosphonate chemistry were developed for their preparation. Synthetic aspects of these transformations and the biological activity of the synthesized compounds are discussed.

Keywords: 2′,3′-dideoxynucleosides; AZT; Anti-HIV; H-Phosphonates; Heteroaromatic amines; Phosphoramidates; Pronucleotides.