Structure, Synthesis, and Biological Activity
Abstract
Incubation of norethindrone1 (I) with the 10,000 g supernatant fraction from liver of phenobarbital-treated beagles led to isolation of two novel norethindrone derivatives: 17β-hydroxy-19-nor-4β, 5β-epoxy-17α-pregn-20-yn-3-one (IIb) and 17β-hydroxy-19-nor-5α,-17α-pregn-20-yne-3,6-dione (V). The compounds were identified by comparison of physical properties (IR, GLC, TLC, MS, and CD) with synthetic substances. IIb was synthesized by base-catalyzed reaction of I with hydrogen peroxide and V by acid-catalyzed rearrangement of 6β, 17β-dihydroxy-19-nor-17α-pregn-4-en-20-yn-3-one (IV). The stereochemistry of IIb and V was established by circular dichroism measurements and that of IV by nuclear magnetic resonance. On subcutaneous administration to mice, IV and V were weak antifertility agents compared to I, and IIb was ineffective at 25 mg/kg/day. All three were no more uterotropic than I.
Footnotes
- Received August 20, 1973.
- Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics