10. Sultine analogues of spirolactones

Antimineralocorticoids

“…its corresponding salt (RU 28318) which needs to he transformed in vivo to the lactonic con figuration in RU 26752 appeared most promis ing in retaining MCR-mediated antagonist ac tivity, yet largely devoid of the aforementioned side effects due to negligible affinity for the androgen and the progesterone receptor [29].…”

“…32]. Although spirorenone was severalfold more active than spiro nolactone in vitro, their affinities for the MCR were comparable [29,31]. Spirorenone, too, has been discontinued as a drug due primarily to its progestational side effect [31J.…”

“…Shortening or lengthening of the 17a-side chain, however, resulted in concurrent loss of both parameters [28]. Introduction of a hydro gen bond acceptor, such as an oxygen atom, in 17(3-position of the D-ring in spiroether re tained both the affinity for the MCR in vitro and antimineralocorticoid activity in vivo [29].…”

“…The antiandrogenic ef fects of spirolactones lead to gynecomastia and impotence in men, whereas its progestomimetic action provokes menstrual abnormalities in women [for reviews, see [28][29][30][31][32]. A very large number of chemical modification was there fore introduced in order to synthesize a spirolactone derivative with antimineralocorticoid activity devoid of the obnoxious side effects [28-321. Major conclusions of potential importance that can be deduced from these exhaustive studies are summarized in table 1.…”

(17S)-Spiro[(androstène-4)-17:5'-(oxathiolane-1',2')] one-3 oxyde-2' (isomère A)

“…Les spirosultines, st~ro'ides en 17, manifestent chez l'animal d'int~ressantes propri~t~s antimin~ralocortico'fdes (Nedelec et al, 1978). Par rapport aux spirolactones correspondantes, ces compos~s pr~sentent la particularit~ d'exister sous deux formes isom~res au niveau de l'atome de soufre et, il a ~t~ observ~ que, in vitro, seule une des deux formes pr~sente une affinit6 pour le r~cepteur de l'aldost6rone.…”