Ferrocene derivatives have attracted significant interest as anticancer, antibacterial, antifungal and antiparasitic drug candidates. Discovered in the 1990s, the two most prominent derivatives, ferroquine and ferrocifen, have since been studied extensively for the treatment of malaria and cancer, respectively. The ferrocenyl moiety in these two compounds participates in important metal-specific modes of action that contribute to the overall therapeutic efficacy of the molecules. Although ferroquine is currently in phase II clinical trials and ferrocifen is in preclinical evaluation, no other ferrocene derivative — in fact, no other non-radioactive organometallic compound of any kind — has advanced into clinical trials. This Perspective delineates strategies for the systematic incorporation of ferrocenyl groups into known drugs or drug candidates, with a view to finding new drug leads. In addition, we provide a critical evaluation of the difficulties associated with obtaining the clinical approval that would enable ferrocene-containing molecules to transition from being synthetic curiosities to effective drugs.

二茂铁衍生物作为抗癌，抗菌，抗真菌和抗寄生虫药物候选物引起了极大的兴趣。自1990年代发现以来，两种最杰出的衍生物，铁喹啉和二茂铁已被广泛研究，分别用于治疗疟疾和癌症。这两种化合物中的二茂铁基部分参与重要的金属特异性作用模式，这些作用模式有助于分子的整体治疗功效。尽管目前二茂铁正处于II期临床试验中，二茂铁正在临床前评估中，但尚无其他二茂铁衍生物（实际上，没有任何其他非放射性有机金属化合物）进入临床试验。此观点描述了将二茂铁基团系统整合到已知药物或候选药物中的策略，以寻找新的药物线索。此外，我们对获得临床批准相关的困难进行了严格的评估，该批准将使含二茂铁的分子从合成的好奇心转变为有效的药物。