Privileged structure-based combinatorial libraries targeting G protein-coupled receptors

Combinatorial chemistry has become a key component of today's drug discovery process. Privileged structures, with their inherent affinity for diverse biological receptors, represent an ideal source of core scaffolds and capping fragments for the design and synthesis of combinatorial libraries targeted at various receptors. GPCRs-distributed widely in the body and involved in many physiological and pathophysiological processes-have been historically among the most popular targets for drug discovery. Numerous privileged structure-based combinatorial libraries have been designed and synthesized, and these libraries have proved to be an extremely powerful tool to aid the rapid discovery and optimization of potent and selective ligands for a wide variety of GPCR targets. This review focuses on recent developments in applying privileged structure-based combinatorial libraries for the discovery and optimization of GPCR ligands and critically evaluates the advantages of the various types of GPCR-targeted libraries.