17alpha-Ethyl-20alpha-and -20beta-dihydroprogesterones and other 17alpha-ethyl-substituted pregnanes as potential contragestational agents.

ABSTRACT

The 17alpha-ethyl-substituted analogs of the two epimeric 20-dihydroprogesterones, allopregnadedione and pregn-5-ene-3,20-dione, were synthesized and evaluated for their possible oral contragestational (postcoital antifertility) activity in the rat. The compounds, though bound strongly to the progesterone receptor in vitro, were inactive preimplantively at 10 mg/kg and postimplantively at 40 mg/kg in vivo.

ABSTRACT

PIP 17alpha-20alpha- and 20beta-dihydroprogesterones and other 17alpha-ethyl-substituted pregnanes as potential contragestational agents were investigated in the rat, and the syntheses of 17 alpha-ethyl-substituted analogs of the 2 epimeric 20-dihydroprogesterones, allopregnanedione and pregn-5-ene-3,20 dione are presented. The compounds were administered orally to 5 rats on Days 1-6 of gestation for studies related to effects on implantation or on Days 9-12 of gestation for studies related to drug effects on pregnancy after implantation. Postmortem examination was carried out between Day 14 and Day 21 of gestation. The compounds were strongly bound to the pr ogesterone receptor in vitro but were inactive preimplantively at 10 mg/kg and postimplantively at 40 mg/kg in vivo.