7alpha-Carboalkoxy steroidal spirolactones as aldosterone antagonists.
A variety of esters of 17-hydroxy-3-oxo-17alpha-pregn-4-ene-7alpha,21-dicarboxylic acid-gamma-lactone (7a) was synthetized in a sequence using the corresponding 3-oxo-4,6-diene (2) as starting material. The methyl (5), ethyl (7c), and isopropyl (7e) esters as well as the C-1 unsaturated methyl ester (8a) showed good oral and subcutaneous activity (MED less than or equal to 0.41 mg). Some general observations on structure-activity relationships are made.
D000284:Administration, Oral; D000315:Adrenalectomy; D000818:Animals; D002942:Circular Dichroism; D003900:Desoxycorticosterone / Q000037:antagonists & inhibitors; D007279:Injections, Subcutaneous; D007783:Lactones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009904:Optical Rotation; D009905:Optical Rotatory Dispersion; D011283:Pregnenes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013141:Spiro Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007783:Lactones; D000451:Mineralocorticoid Receptor Antagonists; D011283:Pregnenes; D013141:Spiro Compounds; D003900:Desoxycorticosterone