**Enamine Barbiturates and Thiobarbiturates as a New Class of Bacterial Urease Inhibitors**

**M. Ali 1, Assem Barakat 1,2,\*, Ayman El-Faham 1,2,\*, Abdullah Mohammed Al-Majid 1, Sammer Yousuf 3, Sajda Ashraf 4, Zaheer Ul-Haq 4, M. Iqbal Choudhary 3,4, Beatriz G. de la Torre 5 and Fernando Albericio 1,6,7,8**


Received: 2 April 2020; Accepted: 15 May 2020; Published: 20 May 2020

**Abstract:** Urease is a therapeutic target associated with several important diseases and health problems. Based on our previous work on the inhibition of glucosidase and other enzymes and exploiting the privileged structure assigned to the (thio)barbiturate (pyrimidine) scaffold, here we tested the capacity of two (thio)barbiturate-based compound collections to inhibit urease. Several compounds showed more activity than acetohydroxamic acid as a standard tested compound. In addition, by means of a conformational study and using the Density Functional Theory (DFT) method, we identified energetically low-lying conformers. Finally, we undertook a docking study to explore the binding mechanism of these new pyrimidine derivatives as urease inhibitors.

**Keywords:** pyrimidine-trione; barbituric; thiobarbituric; urease inhibitors; DFT
