Balzarini Jan, Celen Sofie, Karlsson Anna, de Groot Tjibbe, Verbruggen Alfons, Bormans Guy
Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
Antivir Chem Chemother. 2006;17(1):17-23. doi: 10.1177/095632020601700103.
Thymidine (Thd), 1-beta-D-arabinosylthymine (ara-T) and 3'-fluoro-3'-deoxythymidine (FLT) have been substituted at N-3 by a methyl or a 2-fluoroethyl group. FLT and ara-T are markedly inhibitory against human immunodeficiency virus type 1 (HIV-1) and HIV-2, and herpes simplex virus type 1 (HSV-1) and HSV-2, respectively. Modification at N-3 of these compounds markedly decreases both the antiviral and cytostatic activity of the parent compounds FLT and ara-T except for N-3-(methyl)-Thd that proved highly cytostatic for murine leukaemia L1210 cells. The decreased biological activity of the N-3-substituted pyrimidine nucleoside analogues coincides with a significantly lower affinity of the modified Thd analogues for the cellular and viral (activating) nucleoside kinases.
胸腺嘧啶（Thd）、1-β-D-阿拉伯糖基胸腺嘧啶（ara-T）和3'-氟-3'-脱氧胸腺嘧啶（FLT）的N-3位已被甲基或2-氟乙基取代。FLT和ara-T分别对1型人类免疫缺陷病毒（HIV-1）和2型人类免疫缺陷病毒（HIV-2）以及1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）具有显著抑制作用。这些化合物在N-3位的修饰显著降低了母体化合物FLT和ara-T的抗病毒和细胞生长抑制活性，但N-3-（甲基）-Thd对小鼠白血病L1210细胞具有高度细胞生长抑制作用。N-3位取代的嘧啶核苷类似物生物活性的降低与修饰后的Thd类似物对细胞和病毒（激活）核苷激酶的亲和力显著降低相一致。
