Rudge Emma S, Chan Alex H Y, Leeper Finian J
Yusuf Hamied Department of Chemistry, University of Cambridge Lensfield Road Cambridge CB2 1EW UK
RSC Med Chem. 2022 Mar 1;13(4):375-391. doi: 10.1039/d1md00297j. eCollection 2022 Apr 20.
Pyrophosphates have important functions in living systems and thus pyrophosphate-containing molecules and their more stable bisphosphonate analogues have the potential to be used as drugs for treating many diseases including cancer and viral infections. Both pyrophosphates and bisphosphonates are polyanionic at physiological pH and, whilst this is essential for their biological activity, it also limits their use as therapeutic agents. In particular, the high negative charge density of these compounds prohibits cell entry other than by endocytosis, prevents transcellular oral absorption and causes sequestration to bone. Therefore, prodrug strategies have been developed to temporarily disguise the charges of these compounds. This review examines the various systems that have been used to mask the phosphorus-containing moieties of pyrophosphates and bisphosphonates and also illustrates the utility of such prodrugs.
焦磷酸盐在生物系统中具有重要功能，因此含焦磷酸盐的分子及其更稳定的双膦酸盐类似物有潜力用作治疗包括癌症和病毒感染在内的多种疾病的药物。焦磷酸盐和双膦酸盐在生理pH值下均为多阴离子，虽然这对它们的生物活性至关重要，但也限制了它们作为治疗剂的应用。特别是，这些化合物的高负电荷密度除了通过内吞作用外禁止细胞进入，阻止跨细胞口服吸收并导致在骨骼中螯合。因此，已经开发了前药策略来暂时掩盖这些化合物的电荷。本综述研究了用于掩盖焦磷酸盐和双膦酸盐含磷部分的各种系统，并举例说明了此类前药的效用。
