Screening of anti-progestagens by receptor studies and bioassays

A large number of potential anti-progestational compounds were screened for their ability to bind to the progesterone (MCF-7 cells) and glucocorticoid (IM-9 cells) receptors and for their activity in the pregnancy interruption test in rats. The anti-glucocorticoid activity was assessed by the effect of the compounds on body weight gain, adrenal weight and thymus weight in dexamethasone-treated rats. Of the compounds tested, two (Org 31167 and Org 31343) with the dimethylaminophenyl group at carbon atom 18 of 17 beta-hydroxy-17 alpha-(2-propenyl)-estra-4-en-3-one are equipotent with RU 38486 in the pregnancy interruption test. Both compounds possess lower anti-glucocorticoid activity than RU 38486. Since these compounds are far more active after oral than subcutaneous administration it is very likely that they become activated in the gastro-intestinal tract.