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Published on: May 9, 2025
Design, synthesis, and anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U), 2',3'-dideoxyuridine (ddU)
Youcef Mehellou1, Christopher McGuigan, Andrea Brancale
1Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, UK.
Abstract:
We report the synthesis of 2',3'-didehydro-2',3'-dideoxyuridine (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 compelling evidence for the lack of anti-HIV activity of d4U phosphoramidates, in contrast with the corresponding ddU phosphoramidates.
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