Phosphoryl prodrugs are key compounds in drug development. Biologically active phosphoryl compounds often have negative charges on the phosphoryl group, and as a result, frequently have poor pharmacokinetic (PK) profiles. The use of lipophilic moieties bonded to the phosphorus (or attached oxygen atoms) masks the negative charge of the phosphoryl group, and cleavage of the lipophilic moieties releases the active molecule. The use of prodrugs to improve the PK of active parent molecules is an essential step in drug development. This review highlights promising trends in terminal elimination half-life, C_max, clearance, oral bioavailability, and cLog P in phosphoryl prodrugs. We focus on specific prodrug families: esters, amidates, and ProTides. We conclude that moderating lipophilicity is a key part of prodrug success. This type of evaluation is important for drug development, regardless of clinical application. It is our hope that this analysis, and future ones like it, will play a significant role in prodrug evolution.

磷酰前药是药物开发中的关键化合物。具有生物活性的磷酰基化合物通常在磷酰基上带负电荷，因此通常具有较差的药代动力学 (PK) 曲线。使用与磷键合的亲脂部分（或连接的氧原子）掩盖了磷酰基的负电荷，亲脂部分的裂解释放出活性分子。使用前药来改善活性母体分子的 PK 是药物开发的重要步骤。这篇综述强调了终末消除半衰期、C _max、清除率、口服生物利用度和 cLog P的有希望的趋势在磷酰基前药中。我们专注于特定的前药家族：酯、酰胺化物和 ProTides。我们得出结论，调节亲脂性是前药成功的关键部分。无论临床应用如何，这种类型的评估对于药物开发都很重要。我们希望这种分析以及未来的类似分析将在前药进化中发挥重要作用。