Given the problems the benzoyl guanidine derivative cariporide fortreatment of heart failure (see below) it was reasoned that using a pyrazinoylguanidine core that differs in the aromatic core from cariporide (a benzoylguanidine, Fig. 2) and related NHE1 inhibitors might be a prudent approach toavoid side effects and regulatory issues for drug development. Here, SLC9A1 is linked to heart failure.