2'-取代环丁基核苷和核苷酸作为潜在抗艾滋病毒药物的合成与评价
Synthesis and evaluation of 2'-substituted cyclobutyl nucleosides and nucleotides as potential anti-HIV agents.
作者信息
Li Yongfeng, Mao Shuli, Hager Michael W, Becnel Kimberlynne D, Schinazi Raymond F, Liotta Dennis C
机构信息
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
出版信息
Bioorg Med Chem Lett. 2007 Jun 15;17(12):3398-401. doi: 10.1016/j.bmcl.2007.03.094. Epub 2007 Apr 3.
Abstract
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 showed good activity not only against wild-type and recombinant HIV RT (IC(50)=4.7, 6.9 microM), but also against the M184I and M184V mutants (IC(50)=6.1, 6.9 microM) in cell-free assays.
摘要
通过使用不同的[2+2]环加成方法构建核心环丁基环，高效制备了一系列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衍生物，并针对野生型和突变型HIV逆转录酶（RT）进行了评估。虽然核苷类似物在培养物中对HIV-1无活性，但该核苷酸不仅在无细胞试验中对野生型和重组HIV RT表现出良好活性（IC(50)=4.7、6.9 microM），而且对M184I和M184V突变体也有活性（IC(50)=6.1、6.9 microM）。
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