Myocardial ischemia/reperfusion injury is a serious problem involved in cardiovascular diseases. There data which indicate that some steroids induce cardioprotective effects on myocardial ischemia-reperfusion injury; however their activity and the molecular mechanism involved on myocardial ischemia-reperfusion injury are very confusing. Therefore, in this study some estrogen derivatives (compound 3 to 7) were synthesized with the objective of evaluating its activity on myocardial ischemia/reperfusion injury using an isolated heart model. Additionally, molecular mechanism involved in the activity exerted by the compounds 3 to 7 on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in absence or presence of following compounds; prazosin, metoprolol, indomethacin and nifedipine. The results showed that 7 reduce infarct size compared with the estrone and other estrogen derivatives (compounds 3, 4, 5, and 6). Other results showed that 7 significantly increase the perfusion pressure and coronary resistance in isolated heart in comparison with estrone, 3, 4, 5, and 6. Finally, other data indicate that 7 increased the left ventricular pressure in a dose-dependent manner; however, this phenomenon was significantly inhibited by nifedipine. In conclusion, all these data suggest that 7 exert a cardioprotective effect through calcium channels activation and consequently induce changes in the left ventricular pressure levels. This phenomenon results in decrease of myocardial necrosis after ischemia and reperfusion.