Several derivatives of the highly active aldosterone antagonists dihydrospirorenone (2) and spirorenone (3) were synthesized. The purpose of these efforts was to prepare compounds exhibiting reduced endocrinological properties with the same or better aldosterone antagonistic activity than that of spirorenone. The 1 alpha,2 alpha-methylene derivative 20 has a similar aldosterone antagonistic potency compared to that of spirorenone but does not show decreased endocrinological side effects. Other substituents as in compounds 4-11, 15-19, and 21 sharply decreased the aldosterone antagonistic activity of 2 or 3, respectively.

Several derivatives of the highly active aldosterone antagonists dihydrospirorenone (2) and spirorenone (3) were synthesized. The purpose of these efforts was to prepare compounds exhibiting reduced endocrinological properties with the same or better aldosterone antagonistic activity than that of spirorenone. The 1 alpha,2 alpha-methylene derivative 20 has a similar aldosterone antagonistic potency compared to that of spirorenone but does not show decreased endocrinological side effects. Other substituents as in compounds 4-11, 15-19, and 21 sharply decreased the aldosterone antagonistic activity of 2 or 3, respectively.

AbstractDerivate, z.B. (III), (IV), (VI) und (VII), der hochaktiven Aldosteron‐Antagonisten (I) und (II) werden gemäß Formelschema dargestellt.

Publisher Summary This chapter discusses the synthesis and activities of anti-aldosterones. An aldosterone antagonist can prevent or decrease edema formation by competitively inhibiting aldosterone at the receptor level. The antagonist functions as a diuretic agent and causes decreased blood pressure. In a study described in the chapter, the anti-aldosterone activity of a bis-methylene derivative was compared to that of spironolactone by a method involving a continuous i.v. infusion of aldosterone in rats and in man. In this study, adrenalectomized rats were pretreated with fluocortolone caproate and fluocortolone. Five days after adrenalectomy, these rats received a continuous infusion of aldosterone. Spironolactone and a bis-methylene derivative were given orally l h before beginning aldosterone infusion. Urine production, volume and electrolyte concentration were measured hourly. The bis-methylene derivative was found to reverse the strong depression of the urinary Na/K ratio induced by the mineralocorticoid effect of aldosterone in a dose-dependent manner and had more than five times the potency of spironolactone. A study with healthy human subjects also confirmed this result.

Chemischer InformationsdienstVolume 13, Issue 50 Natural Products ChemInform Abstract: SYNTHESIS OF A NEW HIGHLY EFFECTIVE ALDOSTERONE ANTAGONIST (SPIRORENONE) D. BITTLER, D. BITTLERSearch for more papers by this authorH. HOFMEISTER, H. HOFMEISTERSearch for more papers by this authorH. LAURENT, H. LAURENTSearch for more papers by this authorK. NICKISCH, K. NICKISCHSearch for more papers by this authorR. NICKOLSON, R. NICKOLSONSearch for more papers by this authorK. PETZOLDT, K. PETZOLDTSearch for more papers by this authorR. WIECHERT, R. WIECHERTSearch for more papers by this author D. BITTLER, D. BITTLERSearch for more papers by this authorH. HOFMEISTER, H. HOFMEISTERSearch for more papers by this authorH. LAURENT, H. LAURENTSearch for more papers by this authorK. NICKISCH, K. NICKISCHSearch for more papers by this authorR. NICKOLSON, R. NICKOLSONSearch for more papers by this authorK. PETZOLDT, K. PETZOLDTSearch for more papers by this authorR. WIECHERT, R. WIECHERTSearch for more papers by this author First published: December 14, 1982 https://doi.org/10.1002/chin.198250283Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume13, Issue50December 14, 1982 RelatedInformation

Angewandte ChemieVolume 94, Issue 9 p. 718-719 Zuschriften Synthese von Spirorenon, einem neuen stark wirksamen Aldosteron-Antagonisten Dieter Bittler, Dieter Bittler Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Helmut Hofmeister, Dr. Helmut Hofmeister Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Henry Laurent, Dr. Henry Laurent Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Klaus Nickisch, Dr. Klaus Nickisch Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Robert Nickolson, Dr. Robert Nickolson Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Karl Petzoldt, Dr. Karl Petzoldt Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorProf. Dr. Rudolf Wiechert, Prof. Dr. Rudolf Wiechert Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this author Dieter Bittler, Dieter Bittler Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Helmut Hofmeister, Dr. Helmut Hofmeister Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Henry Laurent, Dr. Henry Laurent Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Klaus Nickisch, Dr. Klaus Nickisch Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Robert Nickolson, Dr. Robert Nickolson Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorDr. Karl Petzoldt, Dr. Karl Petzoldt Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this authorProf. Dr. Rudolf Wiechert, Prof. Dr. Rudolf Wiechert Forschungslaboratorien der Schering AG, Berlin/Bergkamen Müllerstraße 170--178, D-1000 Berlin 65Search for more papers by this author First published: September 1982 https://doi.org/10.1002/ange.19820940923Citations: 24AboutPDF ToolsRequest permissionAdd to favorites ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume94, Issue9September 1982Pages 718-719 This is the German version of Angewandte Chemie. Note for articles published since 1962: Do not cite this version alone. Take me to the International Edition version with citable page numbers, DOI, and citation export. We apologize for the inconvenience. RelatedInformation

Angewandte Chemie International Edition in EnglishVolume 21, Issue 9 p. 696-697 Communication Synthesis of Spirorenone—A Novel Highly Active Aldosterone Antagonist Dr. Dieter Bittler, Dr. Dieter Bittler Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Helmut Hofmeister, Dr. Helmut Hofmeister Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Henry Laurent, Dr. Henry Laurent Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Klaus Nickisch, Dr. Klaus Nickisch Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Robert Nickolson, Dr. Robert Nickolson Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Karl Petzoldt, Dr. Karl Petzoldt Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorProf. Dr. Rudolf Wiechert, Corresponding Author Prof. Dr. Rudolf Wiechert Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this author Dr. Dieter Bittler, Dr. Dieter Bittler Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Helmut Hofmeister, Dr. Helmut Hofmeister Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Henry Laurent, Dr. Henry Laurent Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Klaus Nickisch, Dr. Klaus Nickisch Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Robert Nickolson, Dr. Robert Nickolson Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorDr. Karl Petzoldt, Dr. Karl Petzoldt Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this authorProf. Dr. Rudolf Wiechert, Corresponding Author Prof. Dr. Rudolf Wiechert Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Forschungslaboratorium der Schering AG Berlin/Bergkamen Müllerstrasse 170–178, D-1000 Berlin 65 (Germany)Search for more papers by this author First published: September 1982 https://doi.org/10.1002/anie.198206961Citations: 12AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume21, Issue9September 1982Pages 696-697 RelatedInformation