Bis-ketol nucleoside triesters as prodrugs of the antiviral nucleoside triphosphate analogues of 3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine.
Bis-ketol nucleoside triesters as prodrugs of the antiviral nucleoside triphosphate analogues of 3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine.
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双酮醇核苷三酯作为 3-脱氧胸苷和 3-脱氧-2,3-二脱氢胸苷的抗病毒核苷三磷酸类似物的前药。
DOI：
10.1081/ncn-120030723
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Koser,GeraldF
中科院分区：
文献类型：
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作者：
Calvo,KimC;Wang,Xiaohong;Koser,GeraldF
制备了 3'-脱氧胸苷 (ddT) 和 3'-脱氧-2',3'-二脱氢胸苷 (d4T) 的衍生物，其中核苷的 5'-羟基被酯化为双酮醇磷酸酯。由此产生的磷酸三酯被认为是相应 5'-单核苷酸的前药，它们是通过两个酮醇酯基团的水解在细胞内形成的。对三酯进行了抗 HIV 活性测试，结果显示，与母体核苷相比，源自 ddT 的三酯显示出增强的抗病毒活性。
Derivatives of 3′‐deoxythymidine (ddT) and 3′‐deoxy‐2′,3′‐didehydrothymidine (d4T) were prepared in which the 5′‐hydroxyl group of the nucleoside was esterified to a bis‐ketol phosphate. The resulting phosphate triesters are postulated to be prodrugs of the corresponding 5′‐mononucleotides, which are formed intracellularly by the hydrolysis of the two ketol ester groups. The triesters were tested for anti‐HIV activity with the result that those derived from ddT showed enhanced antiviral activity when compared to the parent nucleoside.