Synthesis and in vitro enzymatic and antiviral evaluation of phosphoramidate d4T derivatives as chain terminators |
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| Authors: | Yang Shiqiong Pannecouque Christophe Lescrinier Eveline Giraut Anne Herdewijn Piet |
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| Institution: | Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium. |
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| 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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