The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavor that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery, and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery, and its role in the improvement of drug delivery and efficacy.

中文翻译：

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ProTide前药技术：从概念到临床

ProTide技术是一种前药方法，旨在有效地细胞内递送核苷类似物单磷酸酯和单膦酸酯。在这种方法中，单磷酸酯或单膦酸酯基团的羟基被芳香族基团和氨基酸酯部分掩盖，后者在细胞内被酶切掉，释放出游离的核苷单磷酸酯和单膦酸酯类。从结构上讲，这代表了跨越近三十年的广泛药物化学研究的当前终点。它开始于用简单的烷基掩盖核苷单磷酸酯和单膦酸酯基，并发展成为如今众所周知的复杂ProTide系统。这项技术已在药物发现中得到广泛应用，并且已经导致发现了两个FDA批准的（抗病毒）ProTides。在这项工作中，我们将回顾ProTide技术的发展，其在药物发现中的应用以及其在改善药物递送和功效中的作用。