Aldosterone antagonists. 1. Synthesis and biological activities of 11 beta,18-epoxypregnane derivatives.
Several steroid derivatives having the 11 beta,18-epoxypregnane skeleton, 7, 8, 19, 20, 21, and 31, were synthesized to evaluate their antialdosterone activity. Among them, 3-(9 alpha-fluoro-17 beta-hydroxy-3-oxoandrost-4-en-17 alpha-yl)propionic acid gamma-lactone (31) possessed fairly strong binding affinity for the cytoplasmic mineralocorticoid receptor of rat kidney and exhibited good aldosterone antagonist activity in an in vivo assay. However, its agonistic nature cannot be ignored. The properties of 31 as an aldosterone antagonist were enhanced by its very low to negligible binding affinity for the androgen, progestin, estrogen, and glucocorticoid receptors.
Kamata
S
S
Haga
N
N
Mitsugi
T
T
Kondo
E
E
Nagata
W
W
Nakamura
M
M
Miyata
K
K
Odaguchi
K
K
Shimizu
T
T
Kawabata
T
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011278:Pregnanes / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism
D004852:Epoxy Compounds; D000451:Mineralocorticoid Receptor Antagonists; D011278:Pregnanes; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid