The applications of fluorine in drug design continue to expand, facilitated by an improved understanding of its effects on physicochemical properties and the development of synthetic methodologies that are providing access to new fluorinated motifs. In turn, studies of fluorinated molecules are providing deeper insights into the effects of fluorine on metabolic pathways, distribution, and disposition. Despite the high strength of the C–F bond, the departure of fluoride from metabolic intermediates can be facile. This reactivity has been leveraged in the design of mechanism-based enzyme inhibitors and has influenced the metabolic fate of fluorinated compounds. In this Perspective, we summarize the literature associated with the metabolism of fluorinated molecules, focusing on examples where the presence of fluorine influences the metabolic profile. These studies have revealed potentially problematic outcomes with some fluorinated motifs and are enhancing our understanding of how fluorine should be deployed.

中文翻译：

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氟化化合物的代谢和药物方面。

氟在药物设计中的应用不断扩展，这是由于对氟对其理化特性的影响有了更深入的了解，以及合成方法的发展为人们提供了便利，这些方法为获得新的氟化图案提供了可能。反过来，对氟化分子的研究也提供了对氟对代谢途径，分布和处置的影响的更深刻的见解。尽管C-F键具有很高的强度，但氟化物从代谢中间体的离开仍然很容易。这种反应性已在基于机理的酶抑制剂的设计中得到利用，并影响了氟化化合物的代谢命运。在此观点中，我们总结了与氟化分子代谢有关的文献，重点关注氟的存在影响代谢谱的例子。