Employing an optimized Pd-catalyzed cross-coupling reaction promoted by CuI, novel N-ferrocenylpyridazinones along with N-phenyl- and N-(2-pyridyl) analogues were synthesized from readily available heterocyclic precursors, iodoferrocene, iodobenzene and 2-bromopyridine. With exception of the ferrocenylation of 6-ferrocenylpyridazin-3(2H)-one yielding both N- and O-substituted products, the studied reactions exclusively afforded N-aryl lactams. The novel compounds exhibited cytotoxicity towards HEPG2 and HT-29 human malignant cells under in vitro conditions. The measured IC₅₀ values supplemented with the results of cyclic voltammetry and DFT calculations suggest that the cytotoxic activity of the N- and O-ferrocenyl-substituted derivatives and the decreased effect of the N-phenyl analogues seem to be at least partly associated with the potential to generate reactive oxygen species (ROS). This interpretation, allowing the prediction of characteristic substituent-dependent SAR, was supported by the results of related studies on the practically inactive N-(2-pyridyl)pyridazinones assumed to be present in protonated chelate forms with highly a decreased propensity to undergo ionization.

利用CuI促进的优化的Pd催化的交叉偶联反应，从容易获得的杂环前体，碘二茂铁，碘苯和2-溴吡啶合成了新的N-二茂铁基吡啶并酮与N-苯基和N-（2-吡啶基）类似物。除了6-铁茂铁吡啶并嗪-3（2 H）-的铁茂铁化作用同时产生N-和O-取代的产物外，所研究的反应仅提供了N-芳基内酰胺。在体外条件下，新化合物对HEPG2和HT-29人恶性细胞表现出细胞毒性。测得的IC ₅₀值加上循环伏安法和DFT计算的结果表明，N-和O-二茂铁基取代的衍生物的细胞毒活性以及N-苯基类似物的降低的作用似乎至少部分与产生反应性的潜力有关。氧（ROS）。这种解释允许预测特征性的依赖于取代基的SAR，这一解释得到了有关对被认为以质子化螯合物形式存在的几乎无活性的N-（2-吡啶基）吡啶并壬酮的相关研究的结果的支持，并且其经历电离的可能性大大降低。