A series of novel rutaecarpine derivatives were synthesized and subjected to pharmacological evaluation as PDE5 inhibitors. The structure–activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by the molecular docking studies. Among the 25 analogues, compound 8i exhibited most potent PDE5 inhibition with IC₅₀ values about 0.086 μM. Moreover, it also produced good effects against scopolamine-induced cognitive impairment in vivo. These results might bring significant instruction for further development of potential PDE5 inhibitors derived from rutaecarpine as a good candidate drug for the treatment of Alzheimer’s disease.

合成了一系列新的芸苔芸香碱衍生物，并作为PDE5抑制剂进行了药理学评估。讨论了结构与活性之间的关系，并通过分子对接研究进一步阐明了它们的结合构象和同时相互作用方式。在25个类似物中，化合物8i表现出最有效的PDE5抑制作用，IC ₅₀值为约0.086μM。而且，它在体内对抗东pol碱引起的认知障碍也产生了良好的效果。这些结果可能为进一步开发潜在的源自芸苔芸香碱的PDE5抑制剂提供指导，这是治疗阿尔茨海默氏病的良好候选药物。