Huang J T, Chen L C, Wang L B, Kim M H, Warshaw J A, Armstrong D, Zhu Q Y, Chou T C, Watanabe K A, Matulic-Adamic J
Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division of Graduate School of Medical Sciences, Cornell University, New York, New York 10021.
J Med Chem. 1991 May;34(5):1640-6. doi: 10.1021/jm00109a017.
In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3' -difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-methylcytosine analogue 21, 3'-deoxy-2',3'-didehydro-2' -fluorothymidine (25), 3'-azido-2',3'-dideoxy-2'-fluoro-5-methyluridine (29), 2'-azido-3'-fluoro-2',3'-dideoxy-5-methyluridine (31), and 2'3'-dideoxy-2' -fluoro-5-methyluridine (37). These new nucleosides were screened for their activity against HIV and feline TLV in vitro. None of the compounds showed significant activity. It is interesting to note that such a small modification in the sugar moiety of active anti-HIV nucleosides (i.e., displacement of hydrogen by fluorine) almost completely inactivate the agents.
为了获得治疗指数优于齐多夫定、氟替诺福韦或司他夫定的药物，合成了几种抗HIV-1核苷类似物。这些类似物包括2'，3'-二脱氧-2'，3'-二氟-5-甲基尿苷（13）、其阿拉伯糖类似物19、阿拉伯糖-5-甲基胞嘧啶类似物21、3'-脱氧-2'，3'-二脱氢-2'-氟胸苷（25）、3'-叠氮基-2'，3'-二脱氧-2'-氟-5-甲基尿苷（29）、2'-叠氮基-3'-氟-2'，3'-二脱氧-5-甲基尿苷（31）以及2'，3'-二脱氧-2'-氟-5-甲基尿苷（37）。对这些新核苷进行了体外抗HIV和猫白血病病毒活性筛选。这些化合物均未显示出显著活性。值得注意的是，活性抗HIV核苷糖部分如此微小的修饰（即氢被氟取代）几乎完全使这些药物失活。
