Synthesis, Characterization, and Evaluation of Tetrazole Derivatives with Pyrrole‐2,5‐Dione Moieties as Urease Inhibitors: Exploring Structure‐Activity Relationships and Computational Insights

Abstract A series of Tetrazole derivatives containing pyrrole‐2,5‐dione groups ( 5 a – e ) were synthesized and comprehensively characterized using HRMS, FT‐IR, and 1 H−, 13 C‐NMR spectroscopic techniques. These compounds were evaluated for their ability to inhibit urease activity in vitro , demonstrating remarkable inhibitory potential with IC 50 values ranging from 4.325±1 to 18.28±1 μM, surpassing the standard thiourea (IC 50 =17.386±1 μM). Notably, compounds 5 b (IC 50 =4.325±1 μM), 5 e (IC 50 =7.411±1 μM), 5 c (IC 50 =9.313±1 μM), and 5 a (IC 50 =10.46±1 μM) exhibited notably higher activity compared to the standard thiourea. In our exploration of the structure‐activity relationship (SAR), we investigated the impact of differently substituted aryl rings on inhibitory potential. Our results highlight the crucial role of substituent positioning on the aryl ring, independent of the nature of the substituents. Additionally, computational studies were conducted on all compounds, supporting our experimental findings. Molecular docking simulations revealed a strong correlation between biological evaluation results and computational predictions, affirming the promising inhibitory activity of the compounds.