Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
Eur J Med Chem. 2009 Nov;44(11):4648-53. doi: 10.1016/j.ejmech.2009.06.037. Epub 2009 Jul 4.
A series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives were synthesized and evaluated as potent inhibitors of HIV-1. Among the newly disclosed TTAs, compounds 7f, 7 g and 7c were the most potent inhibitors of HIV-1 replication of the series (EC(50)=0.17+/-0.02, 0.36+/-0.19 and 0.39+/-0.05 microM, respectively), coupled with a reasonable selectivity index (SI>1452, >845, and >774, respectively). They possess improved or similar HIV-1 inhibitory activity compared with NVP (EC(50)=0.208 microM) and DLV (EC(50)=0.320 microM). The preliminary structure-activity relationships among the newly synthesized congeners are discussed briefly and rationalized by docking studies.
一系列 2-(4-(萘-2-基)-1,2,3-噻二唑-5-基硫代)乙酰胺(TTA)衍生物被合成并评估为强效 HIV-1 抑制剂。在所披露的新 TTAs 中，化合物 7f、7g 和 7c 是该系列中对 HIV-1 复制抑制作用最强的化合物(EC(50)=0.17+/-0.02、0.36+/-0.19 和 0.39+/-0.05 microM)，具有合理的选择性指数(SI>1452、>845 和>774)。与 NVP(EC(50)=0.208 microM)和 DLV(EC(50)=0.320 microM)相比，它们具有改善或相似的 HIV-1 抑制活性。简要讨论了新合成同类物之间的初步构效关系，并通过对接研究进行了合理化。
