Alanazi Ashwag S, Miccoli Ageo, Mehellou Youcef
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, Cardiff CF10 3NB, U.K.
J Med Chem. 2021 Nov 25;64(22):16703-16710. doi: 10.1021/acs.jmedchem.1c01490. Epub 2021 Nov 4.
Intracellular phosphorylation of therapeutic nucleoside analogues into their active triphosphate metabolites is a prerequisite for their pharmacological activity. However, the initial phosphorylation of these unnatural nucleosides into their monophosphate derivatives can be a rate-limiting step in their activation. To address this, we herein report the development of the aryloxy pivaloyloxymethyl prodrugs (POMtides) as a novel and effective nucleoside monophosphate prodrug technology and its successful application to the anticancer nucleoside analogue 5-fluoro-2'-deoxyuridine (FdUR).
治疗性核苷类似物在细胞内磷酸化为其活性三磷酸代谢物是其药理活性的先决条件。然而，这些非天然核苷最初磷酸化为其单磷酸衍生物可能是其激活过程中的限速步骤。为了解决这个问题，我们在此报告芳氧基新戊酰氧甲基前药（POMtides）作为一种新型有效的核苷单磷酸前药技术的开发及其在抗癌核苷类似物5-氟-2'-脱氧尿苷（FdUR）上的成功应用。
