Herdewijn Piet
Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Antiviral Res. 2006 Sep;71(2-3):317-21. doi: 10.1016/j.antiviral.2006.04.004. Epub 2006 Apr 27.
Nucleoside analogues have been the most successful antiviral compounds. Likewise, they are the most intriguing antiviral compounds, because of their structural relationship to natural nucleosides. This is also the reason why the design process of a potential selective antiviral nucleoside is so difficult. Too many natural processes (from cellular uptake to DNA incorporation) and too many enzymes are involved in their biological effect (activity/toxicity/catabolism/anabolism) to make the design process readily predictable. The relationship between the physicochemical and biochemical properties of nucleoside analogues and their antiviral activity is very complex and could only be understood on a very long term basis. Here we try to explain some of the reasoning that was made during the design process leading to new potent antivirals with a phosphonate functionality.
核苷类似物一直是最成功的抗病毒化合物。同样，它们也是最引人入胜的抗病毒化合物，因为它们与天然核苷存在结构关系。这也是设计潜在的选择性抗病毒核苷如此困难的原因。在其生物学效应（活性/毒性/分解代谢/合成代谢）中涉及太多自然过程（从细胞摄取到DNA掺入）和太多酶，以至于设计过程难以轻易预测。核苷类似物的物理化学和生化性质与其抗病毒活性之间的关系非常复杂，只能从长期角度去理解。在此，我们试图解释在设计过程中所做的一些推理，这些推理促成了具有膦酸酯官能团的新型强效抗病毒药物的诞生。
