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Steroidal, Aldosterone Antagonists: Increased selectivity of 9α,11‐epoxy derivatives
Author(s) -
Grob Jürgen,
Boillaz Michel,
Schmidlin Julius,
Wehrli Hansuli,
Wieland Peter,
Fuhrer Hermann,
Rihs Grety,
Joss Urs,
Gasparo Marc De,
Haenni Henry,
Ramjoué Hans Peter,
Whitebread Steven E.,
Kalvoda Jaroslav
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800220
Subject(s) - chemistry , aldosterone , in vivo , mineralocorticoid , steroid , excretion , mineralocorticoid receptor , epoxy , receptor , selectivity , pharmacology , endocrinology , medicine , stereochemistry , biochemistry , hormone , organic chemistry , catalysis , microbiology and biotechnology , biology
In the search for aldosterone antagonists with an optimal activity profile, twelve 9α, 11‐epoxy‐steroids were prepared and compared with their 9α, 11α ‐unsubstituted analogues in terms of steroid receptor binding in vitro and electrolyte excretion in vivo. Substitution of the parent structures by an epoxy group at positions 9α, 11 resulted in marginal effects on mineralocorticoid receptor binding and electrolyte excretion, but greatly reduced androgen and gestagen receptor binding. This finding is reflected in the largely lacking unwanted anti‐androgenic and gestagenic side effects in animal models of the three most interesting 9α, 11 ‐epoxy‐spirolactones 4 (CGP 33033), 18 (CGP 29245), and 25 (CGP 30083).