30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development

  1. Lars Bärfacker2
  1. 1Drug Discovery, Cardiology Research, Bayer AG, Wuppertal, Germany
  2. 2Drug Discovery, Medicinal Chemistry, Bayer AG, Wuppertal, Germany
  1. Correspondence should be addressed to P Kolkhof; Email: peter.kolkhof{at}bayer.com
  1. Figure 1

    Important steroidal MRAs. Chemical structures of the most important 17-spirolactone derivatives, which were discovered and published between 1957 (beginning on top of the figure) and 1987 are shown. Launched drug compounds are highlighted by a white background. Open-ring potassium salt derivatives are highlighted by a light grey background (note that potassium canrenoate is both, a launched drug and a potassium salt derivative). Active metabolites are highlighted by a darker grey background. Arrows indicate either the generation of respective active metabolites from spironolactone (to different quantitative amounts, indicated by respective arrow sizes) or the equilibrium of the open-ring potassium salts with the respective lactone metabolite. Note the structural similarities of several stacked derivatives, e.g. mexrenone and eplerenone, or spironolactone and mespirenone.

  2. Figure 2

    Novel non-steroidal MRAs in clinical development. Chemical structures of the three clinically most advanced non-steroidal MRAs apararenone, esaxerenone and finerenone are shown (from left to right).

  3. Figure 3

    60 years of research and development on MRAs. The time bar highlights relevant publications on the discovery of MRAs or important clinical trial results with MRAs (RALES, EPHESUS, EMPHASIS-HF, ARTS, ARTS-DN and ARTS-HF) in a given year. Note that cloning of MR was at midway within the 60 years of R&D on MRAs.

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