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Home > Scientific articles
Apr 2025

Spirocyclic compounds as innovative tools in drug discovery for medicinal chemists

European Journal of Medicinal Chemistry

by Varela MT, Dias GG, de Oliveira LFN, de Oliveira RG, Aguiar FD, Nogueira JP, Cruz LR, Dias LC. European Journal of Medicinal Chemistry 2025; 287:117368. doi: 10.1016/j.ejmech.2025.117368.

Summary: Spirocyclic motifs allow the improvement of drug-like properties and are increasingly being included in clinical candidates and approved drugs. Spirocycles are becoming widely accessible to medicinal chemists as the number of synthetic methodologies and building blocks available is increasing. From restricting conformation to induce a better fit with the target, to modulation of physicochemical and pharmacokinetic properties, spirocycles are being used to address several challenges in drug discovery. The authors of this review describe general aspects of the chemistry of spirocycles, highlighting some key strategies for their preparation, and demonstrate that, beyond the exploration of structure-activity relationships in medicinal chemistry, the use of spirocycles is an attractive approach for enhancing properties such as potency, selectivity, physicochemistry, and pharmacokinetics.

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