S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: synthesis, antiviral activity, and stability study.
S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: synthesis, antiviral activity, and stability study.
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AZT 的 S-酰基-2-硫乙基芳基磷酸三酯衍生物：合成、抗病毒活性和稳定性研究。
DOI：
10.1021/jm021016y
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发表时间：
2003
影响因子：
7.3
通讯作者：
C. Périgaud
中科院分区：
文献类型：
--
作者：
S. Peyrottes;G. Coussot;I. Lefebvre;J. Imbach;G. Gosselin;A. Aubertin;C. Périgaud
报道了含酪氨酸修饰的3 '-叠氮基-2'，3 '-双脱氧胸苷（AZT）磷酸三酯衍生物的合成、抗病毒活性和稳定性研究。这些化合物通过亚磷酰胺（P（III））化学从适当的芳基前体获得。所有衍生物的体外抗HIV活性进行了评估，他们似乎是有效的抑制剂的HIV-1复制在各种细胞培养实验中，EC（50）值之间的微和纳摩尔范围内，特别是在胸苷激酶缺陷（TK（-））细胞，显示其作为monoproptide前药的能力。提出的这些混合单核苷酸芳基磷酸三酯的分解过程依次涉及酯酶和磷酸二酯酶水解。
The synthesis, antiviral activity, and stability study of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing modified l-tyrosinyl residues are reported. These compounds were obtained via phosphoramidite (P(III)) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments, with EC(50) values between the micro- and nanomolar range, especially in thymidine kinase deficient (TK(-)) cells, showing their ability to act as mononucleotide prodrugs. The proposed decomposition process of these mixed mononucleoside aryl phosphotriesters successively involves an esterase and a phosphodiesterase hydrolysis.