The ProTide Prodrug Technology: From the Concept to the Clinic.
The ProTide Prodrug Technology: From the Concept to the Clinic.
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DOI：
10.1021/acs.jmedchem.7b00734
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发表时间：
2018-03-22
影响因子：
7.3
通讯作者：
Balzarini J
中科院分区：
文献类型：
--
作者：
Mehellou Y;Rattan HS;Balzarini J
磷酰胺酯前药技术是一种开发用于核苷类似物单磷酸盐和单膦酸盐的有效细胞内递送的前药方法。在这种方法中，单磷酸酯或单膦酸酯基团的羟基被芳族基团和氨基酸酯部分掩蔽，其在细胞内被酶促裂解以释放游离的核苷单磷酸酯和单膦酸酯物质。从结构上讲，这代表了近三十年来广泛的药物化学奋进的当前终点。它开始于用简单的烷基掩蔽核苷单磷酸和单膦酸酯基团，并发展成今天已知的复杂的磷酰胺酯前药系统。这项技术已被广泛用于药物发现，并已导致两个FDA批准的（抗病毒）ProTides的发现。在这项工作中，我们将回顾磷酰胺酯前药技术的发展，其在药物发现中的应用，以及其在改善药物递送和疗效方面的作用。
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.
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