Laboratoire de Chimie Moléculaire et Thioorganique, UMR CNRS 6507 and FR3038, ENSICAEN, Université de Caen Basse-Normandie, 6 Boulevard du Maréchal Juin, 14050 Caen Cedex, France.
J Med Chem. 2012 Mar 22;55(6):2758-68. doi: 10.1021/jm201694y. Epub 2012 Mar 8.
The synthesis of new class of potential TPase inhibitors containing a difluoromethylphosphonate function as phosphate mimic is reported. This new series was prepared from a readily available fluorinated building block in few steps. Two series were evaluated as potential inhibitors: a linear series and a conformational constrained series. The activity of these multisubstrate inhibitors depends on the size of the spacer introduced between the pyrimidine ring and the phosphonate function. Best results were observed from triazolyl derivatives, easily obtained from propargylthymine and corresponding azides.
本文报道了一类新型潜在的拓扑异构酶 I 抑制剂的合成，该抑制剂含有二氟膦酸酯作为磷酸酯模拟物。这一系列新化合物是由一个易得的氟化砌块经几步反应制备的。这一系列化合物分为两个系列进行评价：线性系列和构象限制系列。这些多底物抑制剂的活性取决于嘧啶环和膦酸酯功能之间引入的间隔基的大小。从三唑基衍生物中观察到了最佳结果，三唑基衍生物可容易地从炔丙基胸腺嘧啶和相应的叠氮化物获得。
