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 (IC₅₀ = 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 (IC₅₀ = 0.19 ± 0.27 μM, SI = 117.00) and EV-D68 (IC₅₀ = 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.

合成了一系列核苷 2'-乙炔-7-脱氮-腺苷 (NITD008) 的氨基磷酸酯衍生物，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-丙氨酸己酯的氨基磷酸酯( 15f )对 EV71 表现出最有希望的活性（IC ₅₀  = 0.13 ± 0.08  μ M），并且比 NITD008 强 4 倍。同时，含有l-丙氨酸的环己酯 ( 15l ) 的衍生物对 EV71 (IC ₅₀  = 0.19 ± 0.27  μ M, SI = 117.00) 和 EV-D68 (IC ₅₀ ) 表现出最有效的活性和高选择性指数 = 0.17 ± 0.16  μ M, SI = 130.76)，均高于 NITD008。结果表明，氨基磷酸酯 15l是最有希望进一步开发作为治疗 EV71 和 EV-D68 感染的抗病毒剂的候选药物。