Recent progress in synthetic and natural COMT inhibitors for neurological disorders

Catechol-O-methyltransferase (COMT) inhibitors have played a crucial role in the development of potent and selective drugs for the treatment of Parkinson’s disease, depression, and anxiety disorders. This review provides a comprehensive analysis of the structure–activity relationship (SAR) of COMT inhibitors, highlighting key structural features and pharmacophoric elements that govern their potency, selectivity, and pharmacokinetic properties. This review also discusses the application of SAR principles in the design and optimization of COMT inhibitors. Our analysis reveals the emergence of novel chemical scaffolds and the potential for COMT inhibitors to address unmet medical needs in neurology and psychiatry. This Perspective serves as a valuable resource for clinicians and researchers, providing insights into the rational design of COMT inhibitors and the development of next-generation therapeutics.