2-Pyridone as privileged scaffold: Advances in drug design and structural modification
Yichun Shi1, Yidan Xu2, Guangjun Yu3
1Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
European Journal of Medicinal Chemistry
|June 29, 2026
Summary
The 2-pyridone scaffold is a versatile framework in drug discovery, showing promise across various diseases like cancer and CNS disorders. This review highlights its role in developing targeted therapeutics, especially kinase inhibitors.
Area of Science:
- Medicinal Chemistry
- Drug Discovery
- Heterocyclic Chemistry
Background:
- The 2-pyridone scaffold is a key heterocyclic framework in medicinal chemistry.
- Existing reviews primarily focus on synthesis, lacking a comprehensive medicinal chemistry overview.
- A detailed survey of 2-pyridone applications is needed.
Purpose of the Study:
- To systematically review the medicinal chemistry applications of 2-pyridone derivatives from 2010-2026.
- To emphasize design strategies, SAR, druggability, and biological activities.
- To provide a reference for rational drug design using the 2-pyridone scaffold.
Main Methods:
- Literature review of 2-pyridone-based compounds (2010-2026).
- Analysis of design strategies and structure-activity relationships (SAR).
- Evaluation of biological activities across various disease areas.
Main Results:
- 2-pyridone derivatives show broad applications in cancer, infectious diseases, CNS, immunological, metabolic, and cardiovascular conditions.
- The scaffold is particularly valuable for developing selective kinase inhibitors.
- Significant advancements in druggability optimization and SAR have been achieved.
Conclusions:
- The 2-pyridone scaffold remains a robust and adaptable platform for novel therapeutic discovery.
- This review serves as a comprehensive resource for developing 2-pyridone-based drug candidates.
- The scaffold offers potential for next-generation therapeutics across multiple disease areas.
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