Synthesis and evaluation of 2′-substituted cyclobutyl nucleosides and nucleotides as potential anti-HIV agents
作者:Yongfeng Li、Shuli Mao、Michael W. Hager、Kimberlynne D. Becnel、Raymond F. Schinazi、Dennis C. Liotta
DOI:10.1016/j.bmcl.2007.03.094
日期:2007.6
A series of 2'-substituted cyclobutyl nucleoside analogs were efficiently prepared by constructing the core cyclobutyl ring using different [2+2] cycloaddition approaches. The triphosphate derivative of a cyclobutyl nucleoside was also synthesized and evaluated against wild-type and mutant HIV reverse transcriptases (RT). Whereas the nucleoside analogs were inactive against HIV-1 in culture, the nucleotide
通过使用不同的[2 + 2]环加成方法构建核心环丁基环,可以有效地制备一系列2'-取代的环丁基核苷类似物。还合成了环丁基核苷的三磷酸酯衍生物,并针对野生型和突变型HIV逆转录酶(RT)进行了评估。核苷类似物在培养物中对HIV-1没有活性,而核苷酸不仅对野生型和重组HIV RT(IC(50)= 4.7,6.9 microM),而且对M184I和M184V突变体(IC (50)= 6.1,6.9 microM)。