Skeletal editing of pyridine for ring transformations

The pyridine ring, functioning as a vital framework in numerous bioactive molecules, has recently witnessed significant advancements in precise skeletal editing, which has brought about a revolutionary change in the field of drug design. This review offers a comprehensive summary of three transformative strategies for the skeletal editing of the pyridine ring: (1) Classical reconstruction of the 6-membered ring facilitates the exchange of carbon and nitrogen within the pyridine ring; (2) Ring expansion to 7-membered systems enables the insertion of the carbon or nitrogen atom; and (3) Ring contraction to 5-membered architectures is achieved through the deletion of the carbon atom. These advanced skeletal editing techniques not only surmount the limitations of traditional structural modifications but also create new prospects for pharmacological optimization. It is expected that this review will serve as an intellectual impetus to inspire further innovation, propelling pyridine chemistry into uncharted territories of drug discovery. This review provides a comprehensive summary of strategies for transforming pyridine ring skeletons into other types of rings through skeletal editing, covering classical 6-membered ring reconstruction, ring expansion to 7-membered systems and ring contraction to 5-membered architectures.