Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5′-α-hydroxyphosphonates

A series of aryl nucleoside α-hydroxylphosphonates was synthesised and evaluated as potential anti-HIV compounds. Their stability and decomposition paths in various media (including cell culture medium) can be controlled both by Ar 1 and Ar 2. These compounds showed high anti-HIV potency and in some cases considerably low cytotoxicity. Aryl nucleoside 5′- H-phosphonates 4 bearing AZT or 2′,3′-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5′-α-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosphonates 2 correlates well with the type and extent of their chemical or enzymatic degradation in culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5′-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides.