Harnessing pyrimidine as a building block for histone deacetylase inhibitors

Histone deacetylase (HDAC) inhibitors are well-established multifaceted bioactive agents against tumors and neurodegenerative disorders. Pyrimidine and its fused and substituted derivatives were employed as a surface recognition moiety of HDAC inhibitors. De facto, the literature was loaded with different success stories of pyrimidine-based HDAC inhibitors that garnered much interest. Provoked by our continuous interest in HDAC inhibitors, we summarized and elaborated on the successful harnessing of the pyrimidine scaffold in this regard. Furthermore, we dissect our perspective that may guide medicinal chemists for an effective future design of more active chemotherapeutic agents with potential clinical applications.

Automated summary

Histone deacetylase (HDAC) inhibitors, particularly those based on the pyrimidine scaffold, have shown great potential as bioactive agents against tumors and neurodegenerative disorders. In this article, we provide a comprehensive overview of the successful utilization of pyrimidine and its derivatives in the development of HDAC inhibitors. We also discuss the perspectives and strategies that may guide medicinal chemists in designing more effective chemotherapeutic agents with potential clinical applications in the future.