【摘要】 HIV逆转录酶是治疗艾滋病的有效靶点 ,核苷 -磷酰氨基酸酯是HIV逆转录酶的有效抑制剂 ,但是这类化合物容易在体内被核酸酶水解 .本研究设计合成了对核酸酶具有抵抗作用的 2′ ,3′ 双脱氢 2′ ,3′ 双脱氧胸苷 5′ 硫代磷酰氨基酸酯化合物 ,这类化合物可以有效地透过细胞膜经过细胞激酶的作用 ,进入HIV逆转录酶的作用位点 ,病毒实验表明该类化合物对MT 4细胞具有较好的抗HIV病毒活性 .报道了 2′ ,3′ 双脱氢 2′,3′ 双脱氧胸苷 5′ 硫代磷酰氨基酸酯化合物的合成 ,及利用NMR ,IR和ESI MS谱进行的结构表征和构象分析更多还原

【Abstract】 Nucleoside reverse transcriptase inhibitors are the only drugs so far approved for the treatment of AIDS. Nucleoside 5′-p hosphorothioates is relatively resistant to enzymatic transformations. Novel 2′ ,3′-didehydro-2′,3′-dideoxythymidine (d4T) 5′-thiophosphoramidates have been prepared by thiophosphorochloridate chemistry. These materials were designe d to act as membrane-soluble prodrugs of the bioactive free nucleotides. In v itro evaluation reveals that the compounds have a pronounced, selective anti -H IV activity in MT-4 cells. The new compounds are characterized by NMR, IR and E SI-MS. The results from NMR experiments indicate that there are anti-orientati on for glycosyl grouping in compounds 5a～5e.更多还原