Steroidal Mineralocorticoid Receptor Antagonists: Synthesis and Biology

The development of selective steroidal mineralocorticoid receptor antagonists with improved pharmacological profiles over existing marketed drugs is an attractive goal. Such compounds offer potential for the treatment of hypertension, heart failure and renal disease. With this aim, new spirolactones were prepared exploring substitutions at carbons 6, 7, 9–11, 15–16 and 21. Spirolactones 11 a and 20 were identified with promising biological profiles. Both compounds restored Na+/K+ ratios to physiological levels in an in vivo model The development of selective mineralocorticoid receptor antagonists as treatments for hypertension, heart failure and renal disease is a desirable goal. With this aim new spirolactones bearing different substitutions at carbon 6, 7, 9–11, 15–16 and 21 were prepared and spirolactones 11 a and 20 with promising in vitro and in vivo biological profiles identified.