Pyrimidine Derivatives as Anticancer Agents: Structural Insights and SAR Studies

The structural variety and associated biological potential of pyrimidine derivatives have made them attractive to medicinal chemists. Due to the various biological activities of Pyrimidine derivatives and structural derivatives of DNA, many researchers have been prompted to explore this area. Substituted Pyrimidine derivatives have a broad range of pharmacological applications, including antimicrobial, anticancer, and anti-inflammatory activities. The pyrimidine ring and its fused derivatives, which include pyrazolo[3,4-d]pyrimidine, pyrido[2,3- d]pyrimidine, quinazoline, and furo[2,3-d] pyrimidine, have generated a great deal of attention due to the high variety of biological potential that they possess. In addition, fused pyrimidines are intended as bioisosteres of purines. As a result, numerous substances, including pyrimidines and fused pyrimidine derivatives, have demonstrated promising anticancer potential. The emergence of multidrug resistance in cancer cells has significantly reduced the effectiveness of numerous anticancer drugs, posing a challenge to cancer treatment. To avoid this issue, researchers are continuously focusing on target-based drug discovery as a promising pathway for developing novel anticancer agents with improved efficacy and selectivity. Specifically, this review will explore various pyrimidine derivatives, examining positional substitutions and fusion with other heterocyclic rings to elucidate how these compounds interact with molecular targets involved in cancer development and progression. By understanding these interactions, researchers can design more potent pyrimidine -based drugs with better target selectivity. Moreover, the review will also explain the structure-activity relationships of various pyrimidine derivatives, providing insights into the structural features that contribute to their anticancer activity. In the past few years, numerous novel pyrimidine derivatives have been developed and studied for their anticancer activities. The primary objective of this review is to evaluate the structureactivity relationship (SAR) of pyrimidine derivatives developed as anticancer agents over the past decade.