Design and Synthesis of N‐Aryl Isothioureas As a Novel Class of Gastric H+/K+‐ATPase Inhibitors

To find new H + /K + ‐ATPase inhibitors for the treatment of peptic ulcer disease, a series of novel N ‐aryl isothiourea derivatives were synthesized and their structures were identified by 1 H NMR and GC‐MS. The effects of these compounds on inhibiting gastric acid secretion were evaluated by the guinea pig stomach mucous membrane study with pantoprazole magnesium as a positive control. The results showed that, of the 37 N ‐aryl isothiourea compounds synthesized, 20 compounds have comparable or stronger gastric acid inhibitory activities than that of pantoprazole magnesium. The quantitative structure–activity relationships (QSARs) of the N ‐aryl isothiourea compounds were also studied by comparative molecular field analysis (CoMFA) computation, and the model structure that was supposed to give more powerful bioactivities was finally predicted.