Design, synthesis, and anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U), 2',3'-dideoxyuridine (ddU) phosphoramidate ProTide' derivatives

We report the synthesis of 2', 3'-didehydro-2, 3'-dideoxyu rid me (d4U) and 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives and their evaluation against HIV- 1 and HIV-2. In addition, we conducted molecular modeling studies on both d4U and ddU monophosphates to investigate their second phosphorylation process. The findings from the modeling studies provide PF compelling evidence for the lack of anti-HIV activity of d4U phosphoramidates, in contrast with the corresponding ddU phosphoramidates. (c) 2007 Elsevier Ltd. All rights reserved.