A review on pyrimidine-based pharmacophore as a template for the development of hybrid drugs with anticancer potential.

The low efficacy and toxicity of traditional chemotherapy, led by drug resistance of targeted anticancer therapies, have mandated the exploration and development of anticancer molecules. In this league, hybrid drugs, owing to their peculiar multitargeted functionality and structural diversity, could serve as vital leads in this quest for drug discovery. They are plausibly found to offer added advantages considering the improved efficacy, low toxicity, and improved patient compliance. Among numerous heterocycles explored, pyrimidine derivatives epitomize as a valuable resource for the hybrid drug development due to their validated efficacy and versatility. The present review discusses the role of pyrimidine, a diversified pharmacophore in drug development and concepts of hybrid drugs. The study covers the recent advancements in pyrimidine-based hybrid pharmacophores. It delves further into the challenges in hybrid drug development and ongoing research in hybrid drug discovery. Furthermore, the challenges faced in developing hybrid molecules, such as their design and optimization complexities, bioavailability and pharmacokinetics issues, target identification and validation, and off-target effects, are discussed.