McGuigan C, Davies M, Pathirana R, Mahmood N, Hay A J
Department of Chemistry, University of Southampton, Highfield, UK.
Antiviral Res. 1994 May;24(1):69-77. doi: 10.1016/0166-3542(94)90053-1.
Novel diaryl phosphate triester derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In particular, novel parasubstituted diaryl phosphate derivatives were prepared. In vitro evaluation revealed the compounds to have a pronounced and selective antiviral effect, the magnitude of which varied considerably with the nature of the aryl substituent. In particular, strongly electron-withdrawing aryl substituents correlate with high anti-HIV potency in C8166 cells. Along with AZT, the compounds are poorly effective in JM cells, which appear to lack thymidine kinase, indicating the phosphates to act as pro-drugs of the nucleoside rather than of the free phosphate.
