Prodrugs of phosphonates and phosphates: crossing the membrane barrier.
Prodrugs of phosphonates and phosphates: crossing the membrane barrier.
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DOI：
10.1007/128_2014_561
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发表时间：
2015
影响因子：
8.6
通讯作者：
Wiemer DF
中科院分区：
文献类型：
--
作者：
Wiemer AJ;Wiemer DF
代谢的很大一部分涉及磷酸酯的转化，包括通向核苷酸和寡核苷酸、碳水化合物、类异戊二烯和类固醇以及磷酸化蛋白质的途径。由于天然底物携带一个或多个负电荷，靶向这些酶的药物通常也必须带电，但小的带电分子除了通过内吞作用外，很难穿过细胞膜。由此产生的二分法刺激了大量的努力来开发有效的前药，这些化合物携带很少或不携带电荷，使它们能够通过生物膜，但一旦进入靶细胞，就能释放母体药物。本章将介绍前药形式的最新研究进展，以及它们应用于上市和开发药物的代表性例子。
A substantial portion of metabolism involves transformation of phosphate esters, including pathways leading to nucleotides and oligonucleotides, carbohydrates, isoprenoids and steroids, and phosphorylated proteins. Because the natural substrates bear one or more negative charges, drugs that target these enzymes generally must be charged as well but small charged molecules can have difficulty traversing the cell membrane other than by endocytosis. The resulting dichotomy has stimulated abundant effort to develop effective prodrugs, compounds that carry little or no charge to enable them to transit biological membranes but then able to release the parent drug once inside the target cell. This chapter will present recent studies on advances in prodrug forms, along with representative examples of their application to marketed and developmental drugs.
DOI：
10.3390/molecules16010552
发表时间：
2011-01-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Ora M;Mäntyvaara A;Lönnberg H
通讯作者：
Lönnberg H