School of Pharmacy and Pharmaceutical Sciences , Cardiff University , Redwood Building , Cardiff CF10 3NB , U.K.
School of Pharmacy, College of Medical and Dental Sciences , University of Birmingham , Edgbaston , Birmingham B15 2TT , U.K.
J Med Chem. 2018 Mar 22;61(6):2211-2226. doi: 10.1021/acs.jmedchem.7b00734. Epub 2017 Aug 24.
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.
ProTide 技术是一种前药方法，用于有效递送入胞核苷类似物单磷酸酯和单膦酸酯。在该方法中，单磷酸酯或单膦酸酯基团的羟基被芳基和氨基酸酯部分掩蔽，这些基团在细胞内被酶切割以释放游离核苷单磷酸酯和单膦酸酯。从结构上看，这代表了一项广泛的药物化学研究的最终成果，该研究跨越了近三十年的时间。它始于用简单的烷基基团掩蔽核苷单磷酸酯和单膦酸酯基团，演变成如今所知的复杂的 ProTide 系统。该技术已广泛应用于药物发现，并且已经导致发现了两种 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、它在药物发现中的应用及其在改善药物递释和疗效方面的作用。
