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
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|