Estradienes and 2-Oxaestradienes. Potent Oral Anabolic-Androgenic Agents

Abstract

Anabolic and myotrophic properties of a series of estradienes were assessed by bioassay in castrated rats employing 17a-methyltestosterone (MT) as the standard. The weights of the seminal vesicles and ventral lobe of the prostate glands were used as independent indicators of androgenic activity. Anabolic activity was determined from the weights of the levator ani muscle. The compounds studied were 17j8-hydroxyestra-4,9(10)-dien-3-one (I), 17a-methyl-17/3-hydroxyestra-4,9(10)-dien-3-one (II), 17/3-hydroxy-2-oxaestra-4,9(10)-dien-3-one (III), and 17a-methyl-l7j3-hydroxy-2-oxaestra-4,9(10)-dien-3-one (IV). The androgenic acitivity of the parent compound (I), estimated by both parameters, was slightly less than the standard, while the myotrophic activities for the test and standard compounds were approximately equal. The 17a-methyl derivative (II) had androgenic and myotrophic relative potencies of 5-7 and 80 times MT, respectively. The 2-oxa analog (III) was 2-9 times as androgenic as MT and 93 times as myotrophic. Activity of this magnitude was surprising in view of the absence of a methyl substituent on C-17 of this compound. The 17a-methyl-2-oxa derivative (IV) was by far the most potent compound tested, being 22-47 times more androgenic and 550 times more myotrophic than MT. Both the 2-oxa (III) and 17a-methyl-2-oxa (IV) derivatives possessed highly favorable myotrophic: androgenic ratios ranging from 11 to 37 (III) or 12 to 25 (IV), respectively, depending on the androgenic organ used in the calculation. (Endocrinology 84: 441, 1969)