TY - JOUR T1 - OXYGENATED NORETHINDRONE DERIVATIVES FROM INCUBATION WITH BEAGLE LIVER JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 58 LP - 64 VL - 2 IS - 1 AU - C. E. COOK AU - M. C. DICKEY AU - H. DIX CHRISTENSEN Y1 - 1974/01/01 UR - http://dmd.aspetjournals.org/content/2/1/58.abstract N2 - 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 ER -