PDF(Pubmed)
Abstract：
The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.
摘要：
FDA已经批准了几种基于氟化核苷药效团的药物，许多药物目前正在临床试验中。含氟核苷(t)提供显著的抗病毒和抗癌活性。氟原子的插入，在核苷(t)ide的碱或糖中，改变其电子和空间参数并改变亲脂性，药效学，和这些部分的药代动力学特性。氟原子限制了药物的氧化代谢，并为核苷（t）的糖苷键提供了酶促代谢稳定性。氟的掺入还证明了在具有增强的生物学特性的受体中的额外的氢键相互作用。本文讨论了FDA批准的药物和正在进行的含氟核苷（t）ide药物候选药物在临床试验中的合成方法和抗病毒活性。
