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

Abstract

Benzylphosphonates of 5 ’ -norcarbocyclic analogue of 2 ’ ,3 ’ -dideoxy-2 ’ ,3 ’ -didehydrouridine and its N 3 -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.