**4. Conclusions**

Based on our previous work addressing the inhibition of glucosidase and taking advantage of the privileged structure associated with the (thio)barbiturate (pyrimidiene) sca ffold, here we have identified compounds with high in vitro anti-urease activity. All conformations of the pyrimidine derivatives were optimized with the B3LYP/6–31G method. The DFT results for the compounds correlated well with the experimental data, which indicated that the presence of the pyridine ring and electron-withdrawing groups, especially halogens (compounds **3m**, **3n**, and **3o**), play an important role in conferring urease inhibition activity. Moreover, the molecular docking studies further helped to explain the experimental results. Because of our findings, compounds **3a**, **3d**, **3h**, **3k**, and **3o** emerge as potential leads for the development of urease inhibitors. In addition, the obtained results confirm that the use of privileged structures for medicinal chemistry programs is an excellent strategy for identifying hits and leads. Further investigation will be carried out in the future for urease enzyme competitive inhibition.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3417/10/10/3523/s1. The details of the synthesis and characterization of the studied compounds; X-ray data of compounds **3b** and **3k**; biological activity assay; docking study protocol and copies of NMR spectra (Figures S1–S21) of the synthesized target compounds are provided as Supplementary materials.

**Author Contributions:** Conceptualization, A.B. and A.E.-F.; Data curation, S.A. and Z.U.-H.; Funding acquisition, A.M.A.-M.; Investigation, M.A. and A.B.; Methodology, M.A.; Software, S.Y., S.A. and Z.U.-H.; Supervision, A.E.-F., M.I.C. and F.A.; Visualization, A.M.A.-M., M.I.C. and B.G.d.l.T.; Writing—original draft, A.B.; Writing—review & editing, A.B., M.I.C., B.G.d.l.T. and F.A. All authors have read and agreed to the published version of the manuscript.

**Funding:** Deanship of Scientific Research at King Saud University, Saudi Arabia, research group No. (RGP-044).

**Acknowledgments:** The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for supporting and funding the research group No. (RGP-044).

**Conflicts of Interest:** The authors declare no conflict of interest.
