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Updated: May 27, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Synthesis and in vitro enzymatic and antiviral evaluation of phosphoramidate d4T derivatives as chain terminators
Shiqiong Yang1, Christophe Pannecouque, Eveline Lescrinier
1Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
Abstract:
The anti-HIV activity of nucleoside analogues is highly related to their substrate specificity for cellular and viral kinase and, as triphosphate, for HIV-RT. A series of phosphoramidate d4T derivatives have been synthesized and evaluated as substrates for HIV-1 RT, and also tested for their in vitro anti-HIV activity. Compounds 2 and 4 are able to inhibit HIV-1 replication to the same extent as d4T and d4TMP in MT-4 cells as well as in CEM/0 cells and CEM/TK(-) cells. The data suggests that these phosphoramidates are hydrolysed to d4T before exerting their antiviral activity.
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