Design, Synthesis, and Structural Analysis of an Inhibitor of the Gastric Proton Pump with a Diaza-tricyclic Skeleton

Abstract

The development of potent K + -competitive acid blockers (P-CABs) as inhibitors of acid gastric secretion attracts much research attention. In this study, the structure-guided design and enantioselective synthesis of P-CABs yielded a diazatricyclic compound with moderate inhibitory activity against the gastric proton pump. The eutomer was experimentally confirmed, consistent with pharmacophore predictions, and its binding mode to the gastric proton pump was elucidated via cryo-electron microscopy.