Key aspects of modern GPCR drug discovery.

G-protein-coupled receptors (GPCRs) are the largest and most versatile cell surface receptor family with a broad repertoire of ligands and functions. We've learned an enormous amount about discovering drugs of this receptor class since the first GPCR was cloned and expressed in 1986, such that it's now well-recognized that GPCRs are the most successful target class for approved drugs. Here we take the reader through a GPCR drug discovery journey from target to the clinic, highlighting the key learnings, best practices, challenges, trends and insights on discovering drugs that ultimately modulate GPCR function therapeutically in patients. The future of GPCR drug discovery is inspiring, with more desirable drug mechanisms and new technologies enabling the delivery of better and more successful drugs.

Synthesis of 4-aminotetrahydropyran scaffolds for drug discovery.

Functionalised tetrahydropyran scaffolds were prepared using a tethered enol-ether Prins cyclisation and elaborated to show their potential use in library synthesis. The key 4-hydroxytetrahydropyran scaffold could be readily manipulated to the 4-azidotetrahydropyran that could be elaborated via copper catalysed azide-alkyne cycloaddition or by reduction to the amine, to provide sp3-rich scaffolds useful for drug discovery.