Recent Advances in Multicomponent Reaction Chemistry: Applications in Small Molecule Drug Discovery

The efficiency of translational small molecule medicinal chemistry campaigns is directly related to the "iterative speed" of the skilled drug hunter. Modern-day file enhancement strategies aim to incorporate compounds possessing fragment-, lead-, or drug-like properties measured by a variety of metrics that have been constantly evolving. This chapter discusses the pros and cons of employing multicomponent reactions (MCRs) to enhance the molecular diversity of in-house screening collections and expedite forward progression of lead molecules toward key milestones associated with "drugging" macromolecular targets of interest for therapeutic benefit. It focuses heavily on both well-established MCRs in the pharmaceutical arena (Passerini reaction, Ugi reaction, Van Leusen reaction, Petasis reaction, and Groebke-Blackburn-Bienaymé (GBB) reaction) and recently discovered enticing reactions, including asymmetric versions. The chemistry underpinning these transformations are also discussed with reference to their biological relevance. The chapter pays particular attention to MCRs utilized to discover clinical candidates or marketed drugs.