It is well known that aldosterone is a crucial hormone, which regulates electrolyte and CD 2314 volume homeostasis. After binding to mineralocorticoid receptors, aldosterone promotes the retention of sodium and water at the expense of potassium excretion, subsequently resulting in the increase of blood volume and hypertension. Moreover, high aldosterone levels also stimulate synthesis and accumulation of collagens in cardiac fibroblasts leading to MF. The resulting increase in myocardial stiffness thereby causes diastolic dysfunction and ultimately heart failure. Therefore, deprivation of aldosterone from its pathological effects is a feasible therapeutic approach to treat the related diseases. Currently, two main pharmacotherapies are clinically implemented to suppress the components of renin-angiotesinaldosterone system, which control the secretion of aldosterone via a negative feedback loop, including angiotensinconverting- enzyme inhibitors such as enalapril and MR antagonists like spironolactone and eplerenone. ACE inhibitors are used for the treatment of hypertension and CHF by down-regulation of angiotensin II and subsequent aldosterone secretion. However, long-term suppressive effects of ACE inhibitors on plasma aldosterone levels are weakened due to the phenomenon known as ����aldosterone escape����. Although a clinical study revealed that blockade of MR by spironolactone has reduced the risk of both morbidity and mortality in patients with severe heart failure, the MR antagonists show severe adverse effects such as gynaecomastia or breast pain due to their steroidal structure exhibiting residual affinity to other steroid receptors. Despite the fact that eplerenone as a selective MR antagonist achieves some improvement in terms of side effects as compared to spironolactone, severe hyperkalemia and weaker potency have been reported. Furthermore, treatment with blockade of MR leaves high levels of aldosterone unaffected, which can result in further exacerbation of heart function in a MR independent nongenomic manner. CYP11B2 is a mitochondrial cytochrome P450 enzyme catalyzing the conversion of 11-deoxycorticosterone to aldosterone in three consecutive steps. Its inhibition was proposed as a new strategy for the treatment of aldosterone related Dihydroergocristine mesylate cardiovascular diseases as early as 1994. Recent in vivo studies in rats have demonstrated that CYP11B2 inhibitors can reduce plasma aldosterone levels. Long-term administration of FAD286 to rats with heart failure improves cardiac haemodynamics and cardiac function, which is more significant than those by spironoloactone. However, FAD286 also shows strong inhibition of CYP11B1 and CYP19, thus urging us to design selective CYP11B2 inhibitors. Our group has designed and synthesized several series of CYP11B2 inhibitors.