Herdewijn P, Balzarini J, Baba M, Pauwels R, Van Aerschot A, Janssen G, De Clercq E
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J Med Chem. 1988 Oct;31(10):2040-8. doi: 10.1021/jm00118a033.
A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.
已合成了一系列碱基修饰的嘧啶3'-叠氮基-2',3'-双脱氧核苷以及3'-取代的嘌呤和嘧啶2',3'-双脱氧核苷，并评估了它们对MT-4细胞中人类免疫缺陷病毒（HIV）复制的抑制活性。以下嘧啶衍生物成为HIV诱导的细胞病变最有效和/或选择性的抑制剂（按选择性降低的顺序排列：3'-叠氮基-3'-脱氧胸苷（AZT）、3'-叠氮基-2',3'-双脱氧尿苷（AzddUrd）、3'-叠氮基-2',3'-双脱氧-5-甲基胞苷（AzddMeCyd）、3'-氟-ddUrd（FddUrd）、3'-氟-ddThd（FddThd）、AzddMeCyd的N4-羟基化衍生物和AzddMeCyd的N4-甲基化衍生物。在嘌呤2',3'-双脱氧核苷中，3'-叠氮基-2',3'-双脱氧鸟苷（AzddGuo）、3'-氟-ddGuo（FddGuo）和3'-氟-2,6-二氨基嘌呤2',3'-双脱氧核苷（FddDAPR）是HIV复制最具选择性的抑制剂。
