The use of the phosphonate motif featuring a carbon-phosphorous bond as bioisosteric replacement of the labile P–O bond is widely recognized as an attractive structural concept in different areas of medicinal chemistry, since it addresses the very fundamental principles of enzymatic stability and minimized metabolic activation. This review discusses the most influential successes in drug design with special emphasis on nucleoside phosphonates and their prodrugs as antiviral and cancer treatment agents. A description of structurally related analogs able to interfere with the transmission of other infectious diseases caused by pathogens like bacteria and parasites will then follow. Finally, molecules acting as agonists/antagonists of P2X and P2Y receptors along with nucleotidase inhibitors will also be covered. This review aims to guide readers through the fundamentals of nucleoside phosphonate therapeutics in order to inspire the future design of molecules to target infections that are refractory to currently available therapeutic options.

使用具有碳-磷键的膦酸酯基序作为不稳定的P-O键的生物等位替代，在药物化学的不同领域中被广泛认为是有吸引力的结构概念，因为它解决了酶稳定性和最小化代谢的基本原理。激活。这篇综述讨论了药物设计中最有影响力的成功，特别强调了核苷膦酸酯及其作为抗病毒和癌症治疗剂的前药。然后将描述能够干扰由病原体如细菌和寄生虫引起的其他传染病的传播的结构相关类似物。最后，还将涵盖充当P2X和P2Y受体激动剂/拮抗剂的分子以及核苷酸酶抑制剂。