Synthesis, Structural Characterization, Biological and Computational Evaluation of Oxazolidin‐2‐one‐Based Carbonylsulfamates as Urease Inhibitors

Abstract A series of new functionalized oxazolidin‐2‐one derivatives was synthesized via the condensation of oxazolidin‐2‐one with chlorosulfonyl isocyanate and various substituted phenols. Their structures were elucidated using IR, 1 H, and 13 C NMR spectroscopies as well as mass spectroscopy, with X‐ray crystallographic data provided for compound 5e. The novel synthesized compounds were screened in vitro for their potential to inhibit the urease; an enzyme that is a crucial target in the development of medications for treating urinary and gastric infections. Compared to standard thiourea, most of the investigated compounds had superior inhibitory action against urease; 5c and 5e compounds which contain 4‐bromophenyl and 4‐nitrophenyl, respectively displayed the best results with an IC 50 values of 70 ± 0 µM and 70 ± 1 µM, while the IC 50 of standard thiourea was 130 ± 0 µM. The in silico computational screening; DFT calculations, molecular docking against urease enzyme (PDB ID: 4H9M), molecular dynamics simulation for 100 ns, and ADME/T properties simulation were estimated to analyze the performance of N ‐substituted oxazolidin‐2‐one derivatives. Based upon our results, good correlations with the experimental findings are found, and 5e is the most promising compound from this series.