Sulfonamides as a Promising Scaffold in Drug Discovery: An Insightful Review on FDA-Approved Molecules, Synthesis Strategy, Medical Indication, and Their Binding Mode.

Sulfonamides have emerged as a versatile and promising scaffold in drug discovery, demonstrating various biological activities and therapeutic applications. Since the discovery of Prontosil in the 1930s, sulfonamide-containing compounds have evolved significantly, leading to numerous Food and Drug Administration (FDA)-approved drugs targeting multiple diseases. This review provides an insightful analysis of FDA-approved sulfonamide-containing molecules from 2011 to 2024, focusing on their synthesis strategies, medical indications, and binding modes. The review highlights the therapeutic potential of sulfonamides in treating viral infections, cancer, inflammatory diseases, ocular diseases, cardiovascular disorders, kidney and liver disorders, and more. The synthesis pathways of sulfonamides are meticulously detailed, showcasing the innovative chemical strategies employed to develop these therapeutic agents. The review also emphasizes the structural diversity of sulfonamide derivatives and their mechanisms of action, including carbonic anhydrase inhibition, Janus kinase (JAK)/signal transducer and activator of the transcription (STAT) pathway modulation, and protease inhibition, among others. This comprehensive review underscores the importance of sulfonamides in modern medicinal chemistry, offering valuable insights into their design, synthesis, and clinical applications. By bridging the gap between chemical synthesis and therapeutic efficacy, this review aims to inspire further research and development in the field, paving the way to discover novel sulfonamide-based drugs with enhanced efficacy and reduced side effects.