National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
Eur J Med Chem. 2021 Dec 15;226:113852. doi: 10.1016/j.ejmech.2021.113852. Epub 2021 Sep 17.
A series of phosphoamidate derivatives of nucleoside 2'-acetylene-7-deaza-adenosine (NITD008) were synthesized and evaluated for their in vitro antiviral activities against the enteroviruses EV71 and EV-D68. The phosphoamidate (15f) containing a hexyl ester of l-alanine exhibited the most promising activity against EV71 (IC = 0.13 ± 0.08 μM) and was 4-times more potent than NITD008. Meanwhile, the derivative containing a cyclohexyl ester of l-alanine (15l) exhibited the most potent activity with high selectivity index against both EV71 (IC = 0.19 ± 0.27 μM, SI = 117.00) and EV-D68 (IC = 0.17 ± 0.16 μM, SI = 130.76), which were both higher than that of NITD008. The results indicated that the phosphoamidate 15l was the most promising candidate for further development as antiviral agents for the treatment of both EV71 and EV-D68 infection.
一系列核苷 2'-乙炔-7-脱氮腺苷（NITD008）的磷酰胺酯衍生物被合成并评估了它们对肠道病毒 EV71 和 EV-D68 的体外抗病毒活性。含有 l-丙氨酸己酯的磷酰胺酯（15f）对 EV71 表现出最有前途的活性（IC = 0.13 ± 0.08 μM），比 NITD008 强 4 倍。同时，含有 l-丙氨酸环己酯的衍生物（15l）对 EV71（IC = 0.19 ± 0.27 μM，SI = 117.00）和 EV-D68（IC = 0.17 ± 0.16 μM，SI = 130.76）均表现出最强的活性和高选择性指数，均高于 NITD008。结果表明，磷酰胺酯 15l 是进一步开发作为治疗 EV71 和 EV-D68 感染的抗病毒药物的最有前途的候选药物。
