Recent applications of hydantoin and thiohydantoin in medicinal chemistry

Hydantoin, imidazolidine-2,4-dione, is a non-aromatic five-membered heterocycle, which is considered a valuable, privileged scaffold in medicinal chemistry. The importance of the hydantoin scaffold in drug discovery has been reinforced by several medicines in clinical use, such as phenytoin, nitrofurantoin, and enzalutamide. Hydantoin has five potential substituent sites, including two hydrogen bond acceptors and two hydrogen bond donors. Two additional attractive features of hydantoin scaffolds are their synthetic feasibility for core scaffolds via established cyclization reactions and their ease of accepting various substituents. Because of these characteristics, many hydantoin derivatives with different substituents have been designed and synthesized and exhibit a broad spectrum of biological and pharmacological activities against, for example, cancers, microbial infections, metabolic diseases, and epilepsy. In this review, recent contributions of hydantoin, thiohydantoin, and selenohydantoin scaffolds to medicinal chemistry are described; some major compounds are presented to emphasize their importance, and their structure-activity relationships (SARs) are briefly addressed. Major discussions are devoted to the structural features or novelty of each scaffold and its SAR. The publications in this review encompass those from 2012 to 2018.