Synthesis and Pharmacological Potential of Pyrimidine Derivatives in Neurodegenerative Diseases

Abstract

Pyrimidine derivatives represent a vital class of heterocyclic compounds with broad pharmacological applications, particularly in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) [1]. These disorders are characterized by progressive neuronal degeneration, oxidative stress, and neurotransmitter imbalance [2]. This review systematically analyzes recent advances (2010-2025) in the synthesis and biological evaluation of pyrimidine-based compounds. Various synthetic methodologies, including cyclization, multicomponent reactions, and nucleophilic substitution, have been employed to generate structurally diverse derivatives [3]. Pharmacological studies demonstrate that these compounds exhibit significant acetylcholinesterase inhibition, antioxidant, anti-inflammatory, and neuroprotective activities [5], [6]. Structure-activity relationship (SAR) analysis indicates that substitution patterns on the pyrimidine ring critically influence biological activity [4]. Overall, pyrimidine scaffolds offer promising potential for the development of multi-target-directed ligands for neurodegenerative diseases.