Oxetanes and Thietanes
Methods in Drug Discovery and Discovering Lead Molecules
Oliver L. Symes,
Hikaru Ishikura,
James A. Bull,
Oliver L. Symes
Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, UK
Search for more papers by this authorHikaru Ishikura
Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, UK
Search for more papers by this authorJames A. Bull
Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, UK
Search for more papers by this authorOliver L. Symes,
Hikaru Ishikura,
James A. Bull,
Oliver L. Symes
Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, UK
Search for more papers by this authorHikaru Ishikura
Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, UK
Search for more papers by this authorJames A. Bull
Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, UK
Search for more papers by this authorFirst published: 26 May 2025
Abstract
Oxetanes are increasingly utilized in ring systems in drug discovery but are yet to be fully validated in synthetic drugs. Thietanes, at different oxidation levels, are less explored and also offer considerable potential. Both possess attractive properties for medicinal chemists including high polarity, marked three-dimensionality, and low molecular weight. Commonly deployed to modulate physicochemical properties of candidates, these small, polar units also present a valuable design element for drug discovery. This chapter will outline the structural and physicochemical properties of oxetane and thietane rings, highlighting information pertinent to medicinal chemists and the potential of the rings as bioisosteres. Through selected case studies, this chapter will then explore the application of oxetanes and thietanes in recent drug discovery campaigns (2017–2023) and medicinal chemistry research. The range of general synthetic strategies used to incorporate the four-membered rings will also be considered.
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