Recent studies reported that Epac1deficient mice were protected against various forms of cardiac stress. We identified the Thieno[2,3-B]Pyridine derivatives as EPAC1 inhibitors that confirmed the beneficial for the treatment of cardiac diseases by these inhibitors. The compounds have the advantage to be selective for the EPAC isoforms. Our finding on the cardioprotective effect of Thieno[2,3-B]Pyridine derivatives in a preclinical model of myocardial I/R injury, highlights the therapeutic potential in cardiac ischemia. Our data also showed that the compounds were helpful in chronic treatment in a mouse model of cardiac remodeling induced by sustained activation of β-ARs.