Ivanov M A, Karpenko I L, Chernousova L N, Andreevskaia S N, Smirnova T G, Aleksandrova L A
Bioorg Khim. 2013 Nov-Dec;39(6):718-27. doi: 10.1134/s1068162013060058.
The interaction of CDI-activated diethyl phosphonoacetate with methyl 4-aminobenzoat or 3,5-difluoromethylphenylamine followed by treatment with Me3SiBr in DMF led to N-aryl aminocarbonylmethyl phosphonates and their ethyl esters. Their coupling with 3'-acetyl-α-thymidine followed by removal of the acetyl groups gave (α-D-thymidine-5'-il) N-[4-(methoxycarbonyl-, aminocarbonyl- and carboxy)phenyl]-aminocarbonylmethyl phosphonates, (α-D-thymidine-5'-il)-[3,5-bis(trifluoromethyl)phenylaminocarbonyl]methyl phosphonate and their ethyl esters. The phosphonates were stable in different conditions, low cytotoxic (in Vero and K562 cells) and were able to penetrate into K562 cells. The only ethyl ester of (α-D-thymidine-5'-il) N-[4-(methoxycarbonyl)phenyl]-aminocarbonylmethyl phosphonate in high concentration (200 μg/mL) inhibited in vitro the growth of laboratory sensitive strain of Mycobacterium tuberculosis H37Rv.
CDI 活化的二乙基膦酰基乙酸酯与 4-氨基苯甲酸甲酯或 3,5-二氟甲基苯胺相互作用，随后在 DMF 中用三甲基硅溴处理，得到 N-芳基氨基羰基甲基膦酸酯及其乙酯。它们与 3'-乙酰基-α-胸苷偶联，随后除去乙酰基，得到（α-D-胸苷-5'-基）N-[4-(甲氧基羰基、氨基羰基和羧基)苯基]-氨基羰基甲基膦酸酯、（α-D-胸苷-5'-基）-[3,5-双（三氟甲基）苯基氨基羰基]甲基膦酸酯及其乙酯。这些膦酸酯在不同条件下稳定，细胞毒性低（在 Vero 和 K562 细胞中），并且能够渗透到 K562 细胞中。（α-D-胸苷-5'-基）N-[4-(甲氧基羰基)苯基]-氨基羰基甲基膦酸酯的唯一乙酯在高浓度（200 μg/mL）下可体外抑制结核分枝杆菌 H37Rv 实验室敏感菌株的生长。
