Synthesis of Quinoline, Isoquinoline Derivatives, and Elucidation of Their Potential Anti‐Alzheimer Activity From the Perspectives of ADMET, Molecular Docking and Network Pharmacology: Research Progress

ABSTRACT

Quinoline and isoquinoline derivatives, owing to their unique heterocyclic skeletons and high structural modifiability, have emerged as important lead compounds for the development of anti‐Alzheimer's disease (AD) drugs. In recent years, significant progress has been made in three areas: efficient synthetic methods, multi‐target anti‐AD effects, and computer‐aided drug design. Computational simulation techniques, particularly molecular docking, ADMET prediction, and network pharmacology, have been deeply integrated into the drug discovery process to elucidate the binding modes of compounds with key targets at an early stage and to screen candidates with favorable drug‐like properties. This review systematically discusses synthetic methods for quinoline and isoquinoline derivatives reported in the past five years, focusing on metal‐catalyzed and photocatalytic cyclization strategies. To address the limitation of existing literature that primarily emphasizes synthetic novelty while paying little attention to relevant pharmacological activities, ADMET analysis, molecular docking, and network pharmacology were further employed to provide supporting evidence for the prediction of the anti‐AD activity of the compounds. Parent structures 18 and 82 exhibited relatively low Vina scores in molecular docking and further demonstrated target interaction networks in network pharmacology analysis, making them the most promising candidates for subsequent in vitro and in vivo experimental studies among the compounds reviewed.