PT - JOURNAL ARTICLE AU - C. E. COOK AU - M. C. DICKEY AU - H. DIX CHRISTENSEN TI - OXYGENATED NORETHINDRONE DERIVATIVES FROM INCUBATION WITH BEAGLE LIVER DP - 1974 Jan 01 TA - Drug Metabolism and Disposition PG - 58--64 VI - 2 IP - 1 4099 - http://dmd.aspetjournals.org/content/2/1/58.short 4100 - http://dmd.aspetjournals.org/content/2/1/58.full SO - Drug Metab Dispos1974 Jan 01; 2 AB - 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. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics