HIV-1 non-nucleoside reverse transcriptase inhibitors: incorporation of benzylphosphonate moiety for solubility improvement

Benzylphosphonates of 5’-norcarbocyclic analogue of 2’,3’-dideoxy-2’,3’-didehydrouridine and its N³-benzyl derivatives with different substituents at the phosphorus atom were designed and synthesized in attempt to improve solubility of potential non-nucleoside reverse transcriptase inhibitor. Solubility of the most hydrophilic representative was 400 mg in 100 ml of 1% DMSO solution in water. The target phosphonates were examined against HIV-1 reverse transcriptase with K_I for all compounds being higher than 100 μM.