Phosphoramidate derivatives of d4T as inhibitors of HIV: The effect of amino acid variation

被引：67

作者：

McGuigan, C ^{[1
]}

Tsang, HW ^{[1
]}

Cahard, D ^{[1
]}

Turner, K ^{[1
]}

Velazquez, S ^{[1
]}

Salgado, A ^{[1
]}

Bidois, L ^{[1
]}

Naesens, L ^{[1
]}

DeClercq, E ^{[1
]}

Balzarini, J ^{[1
]}

机构：

[1] CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM

来源：

ANTIVIRAL RESEARCH | 1997年 / 35卷 / 03期

关键词：

HIV; nucleotide; pro-drug; 2'; 3'-dideoxy-2'; 3'-didehydro thymidine; phosphoramidate;

D O I：

10.1016/S0166-3542(97)00029-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Phosphoramidate derivatives of the nucleoside analogue, 2',3'-dideoxy-2',3'-didehydro thymidine (d4T) have been prepared as potential membrane-soluble pre-drugs of the big-active free phosphate forms. In particular phenyl phosphates, linked via nitrogen to methyl-esterified amino acids, were studied. All compounds were fully characterised by a range of methods (high-field multinuclear NMR, mass spectrometry and high performance liquid chromatography (HPLC)) and were subjected to in vitro evaluation of their anti-HIV efficacy. The nature of the amino acid appeared to be extremely important for the eventual antiviral action. Of the amino acids studied, L-alanine was the most efficacious, whilst L-proline and glycine were particularly poor. However, an unnatural amino acid moiety, dimethylglycine, could substitute for alanine with little or no loss of activity. (C) 1997 Elsevier Science B.V.

引用

页码：195 / 204

页数：10

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