Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, UK.
Bioorg Med Chem. 2010 Apr 1;18(7):2748-55. doi: 10.1016/j.bmc.2010.02.015. Epub 2010 Feb 15.
Ribavirin is a nucleoside analogue with broad antiviral activity. Here we report the synthesis and biological evaluation of novel ribavirin ProTides designed to deliver the bioactive ribavirin monophosphate into cells. Some of the compounds display activity similar to the parent nucleoside against a range of viruses. Enzymatic, cell lysate and preliminary modeling studies have been performed to investigate the lack of enhancement of potency by the ProTides, and these indicate a failure at the final, amino acid cleavage step in the ProTide activation process, leading to inefficient release of the nucleoside monophosphate.
利巴韦林是一种具有广泛抗病毒活性的核苷类似物。在这里，我们报告了新型利巴韦林 ProTide 的合成和生物学评价，旨在将生物活性的利巴韦林单磷酸酯递送到细胞中。一些化合物对一系列病毒的活性与母核类似。已经进行了酶、细胞裂解物和初步建模研究，以研究 ProTide 缺乏增强效力的原因，这些研究表明在 ProTide 激活过程的最后氨基酸切割步骤中失败，导致核苷单磷酸酯的释放效率低下。
