Synthesis and Bioactivity of Substituted Benzoylguanidine Derivatives as Potent Na+/H+ Exchanger Inhibitors

A novel series of substituted benzoylguanidine derivatives were designed and synthesized in order to evaluate their NHE1 inhibitory activity. Most of them were found to inhibit NHE1-mediated platelet swelling in a concentration-dependent manner, and eight compounds showed more potent NHE1 inhibitory activity than Cariporide. Compound 6f with an IC50 value of 1.08×10−10 mol·L−1, was 39 times more potent than lead compound CPU-X-050420 in vitro tests.