Herdewijn P, Balzarini J, De Clercq E, Pauwels R, Baba M, Broder S, Vanderhaeghe H
J Med Chem. 1987 Aug;30(8):1270-8. doi: 10.1021/jm00391a003.
A series of 2',3'-unsaturated and 3'-substituted 2',3'-dideoxynucleoside analogues of purines and pyrimidines have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV). The 2',3'-unsaturated analogues of 2',3'-dideoxycytidine (ddeCyd) and 2',3'-dideoxythymidine (ddeThd), 3'-azido-2',3'-dideoxythymidine (AzddThd), 3'-fluoro-2',3'-dideoxythymidine, 2',3'-dideoxycytidine (ddCyd), and 2',3'-dideoxyadenosine (ddAdo) emerged as the most potent inhibitors of HIV-induced cytopathogenicity in the human T lymphocyte cell lines ATH8 and MT4. In ATH8 cells ddCyd, ddeCyd, and ddAdo had the highest therapeutic index whereas in MT4 cells AzddThd, ddThd, ddCyd, and ddAdo were the most selective. Derivatives from ddThd in which the substituent group was linked to the 3'-carbon atom via a thio, sulfonyl, or oxygen bridge were far less inhibitory to HIV than was AzddThd.
已经合成了一系列嘌呤和嘧啶的2'，3'-不饱和及3'-取代的2'，3'-二脱氧核苷类似物，并对其抗人免疫缺陷病毒（HIV）的抑制活性进行了评估。2'，3'-二脱氧胞苷（ddeCyd）和2'，3'-二脱氧胸苷（ddeThd）的2'，3'-不饱和类似物、3'-叠氮基-2'，3'-二脱氧胸苷（AzddThd）、3'-氟-2'，3'-二脱氧胸苷、2'，3'-二脱氧胞苷（ddCyd）和2'，3'-二脱氧腺苷（ddAdo），在人T淋巴细胞系ATH8和MT4中表现为HIV诱导的细胞病变最有效的抑制剂。在ATH8细胞中，ddCyd、ddeCyd和ddAdo具有最高的治疗指数，而在MT4细胞中，AzddThd、ddThd、ddCyd和ddAdo是最具选择性的。ddThd的衍生物，其中取代基通过硫桥、磺酰桥或氧桥与3'-碳原子相连，对HIV的抑制作用远低于AzddThd。
