Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
Org Biomol Chem. 2012 Jan 7;10(1):146-53. doi: 10.1039/c1ob06214j. Epub 2011 Nov 8.
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.
核苷类似物的抗 HIV 活性与其对细胞和病毒激酶的底物特异性高度相关，并且作为三磷酸酯，与 HIV-RT 相关。已经合成了一系列膦酰胺 d4T 衍生物，并将其作为 HIV-1 RT 的底物进行了评估，同时还测试了它们的体外抗 HIV 活性。化合物 2 和 4 能够像 d4T 和 d4TMP 一样抑制 MT-4 细胞以及 CEM/0 细胞和 CEM/TK(-)细胞中的 HIV-1 复制。数据表明，这些膦酰胺在发挥抗病毒活性之前被水解为 d4T。
