ABSTRACT
Multicomponent reactions (MCRs) have emerged as a powerful new strategy in synthetic organic chemistry and drug discovery. Multicomponent reactions can be subcategorized into two general classes, isocyanide-based multicomponent reactions (IMCRs) and non-isocyanide-based multicomponent reactions (NIMCRs). Both reactions offer cost-effective and rapid access to generate molecular libraries. The Gewald 3-CR (G-3CR) of cyanoacetic acid derivatives, active methylene carbonyls, and elemental sulfur is a popular MCR often used in drug discovery yielding 2-amino-3-carbonyl thiophenes. Additionally, Gewald products can be easily transformed into more complex scaffolds by secondary transformations. Nowadays, most multicomponent reactions being performed with isocyanides are based on the classical Passerini and Ugi reactions. Synthesis of kinase inhibitors is another area of the successful application of MCR reactions for large-scale production of clinical candidates. P38α MAP kinases are heavily involved in cytokine-mediated progression of rheumatoid arthritis, autoimmune diseases, and, most importantly, cancer. DNA topoisomerases are the targets of important anticancer and antibacterial drugs.
