FDA-Approved Pyrimidine-Containing Drugs: Synthesis and Clinical Application

Since 2013, a rapidly expanding portfolio of U.S. Food and Drug Administration (FDA)-approved drugs has highlighted pyrimidine as one of the most versatile and therapeutically valuable heteroaromatic scaffolds. Building on more than six decades of medicinal chemistry, these recent approvals underscore the pivotal role of pyrimidines in modern drug discovery across oncology, anti-infectives, immunology, immuno-oncology, neurological disorders, chronic pain, and metabolic diseases. This review systematically surveys pyrimidine-containing drugs approved from 2013 to the present, detailing their synthetic strategies, key biological targets, and disease-specific mechanisms of action. This review demonstrates the enduring value of pyrimidine as a privileged chemotype and bioisostere for phenyl and other aromatic π-systems, offering insights to guide the design of next-generation therapeutics for conditions once considered intractable.