Biological Activities of 16α,17α Dihydroxyprogesterone Derivatives

Summary

The 16α, 17α acetophenane (P-DHP) and acetone (A-DHP) derivatives of 16α, 17α-dihydroxyprogesterone (DHP) and their 6α-methyl, 6β-methyl, 6α-fluoro and 6β-fluoro analogues were assayed for parenteral and oral progestational activity. P-DHP and A-DHP are equal in parenteral activity, each being about twice as potent as progesterone. P-DHP is strongly active orally, being 1 to 2 times as active as nore-thisterone, whereas A-DHP has only weak oral activity. Parenteral activity of P-DHP or A-DHP was not altered by 6-methylation. Oral activity of 6β-methyl-P-DHP was similar to P-DHP but both 6α and 6β-methyl-A-DHP were more potent orally than A-DHP. 6α fluorination had little or no enhancing effect on either parent compound when parenterally administered but did reduce oral potency. 6β fluorination made both parent steroids inactive by either route of administration. P-DHP and A-DHP have longer duration of activity than progesterone, moderate progestational effects still being present 25 days and 20 days, respectively, following a single 10 mg intramuscular injection. P-DHP is devoid of inherent androgenic, anti-androgenic, estrogenic, anti-DCA or corticoid activities.