RT Journal Article
SR Electronic
T1 OXYGENATED NORETHINDRONE DERIVATIVES FROM INCUBATION WITH BEAGLE LIVER
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 58
OP 64
VO 2
IS 1
A1 C. E. COOK
A1 M. C. DICKEY
A1 H. DIX CHRISTENSEN
YR 1974
UL http://dmd.aspetjournals.org/content/2/1/58.abstract
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