All aspects of the drug discovery process have undergone radical changes in the past two decades. In response to the need to discover valuable, pharmacologically useful compounds and to shorten the time required for preclinical research, medicinal chemists have incorporated successful new concepts and methodologies into the laborious process of lead discovery and lead optimization. Selectivity, atom economy, time savings, environmental friendliness, cost-effectiveness, diversity, and drug-like properties, as well as the reconciliation of molecular complexity with experimental simplicity, are some of the key pieces of the puzzle that must be assembled by modern medicinal chemists to achieve the maximum efficiency during drug discovery programs.
Most of these characteristics are met by multicomponent reactions, which have emerged as powerful strategies in contemporary drug discovery since they constitute powerful tools for creating molecular diversity by matching the space of biological targets with relevant chemistry. MCRs allow the generation of a high level of structural and functional complexity in a few steps from simple starting materials without the need to isolate intermediates. Additionally, the absence of workup and purification steps and the minimization of waste promotes time-efficiency when a premium is placed on speed during the drug discovery process.
During the last decade we have exploited the advantages of MCR in our synthetic and medicinal chemistry programs. In this context we have published conceptually novel multicomponent-based reactions to assemble diverse heterocyclic libraries. In parallel, our group has documented diverse MCR approaches in GPCR medicinal chemistry, with novel pharmacophores described for different targets and the reinterpretation and refinement of hit compounds.