Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.

Abstract Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori . However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N -(3,4-dihydroxybenzyl)-4-nitroaniline ( 4 ) was evaluated in detail and shows promising features for development as anti- H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC 50  = 0.62 ± 0.04 and 1.92 ± 0.09 μM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO 2 will result in a moderate to dramatic decrease in potency.