Correlation of structure and potential pharmacological activity of spirohidantoins derived from α-Tetralone

Hydantoin is a nonaromatic five-membered heterocycle, which is considered a valuable, privileged scaffold in medicinal chemistry. The importance of the hydantoin scaffold in drug dis-covery has been reinforced by several medicines in clinical use, such as anticonvulsants (phenyto-in), antibiotics (nitrofurantoin), anticancer drugs (enzalutamide) and keratolytics (allantoin). To design new potentially pharmacologically active compounds, six spirohydantoin derivatives were synthetized and fully characterized by determination of the melting points, elemental analysis, FT-IR, 1H and 13C NMR spectroscopic methods. Effects of the substituents on the shift of the absorp-tion maxima of synthetized compounds were analyzed using the linear solvatation energy relation-ship, while the influence of the chemical structure on the pharmacokinetically relevant properties of the investigated spirohydantoin derivatives was evaluated using the Lipinski’s rule of five, Veber, Egan and Ghose’s empirical criteria, as well as different in silico methods. In order of de-tailed analysis of the potential pharmacological activity of the synthesized spirohydantoins, their potential pharmacological properties were correlated with the corresponding solvent effects.