Spectral and chromatographic properties of 2-methoxyphenylmetyrapone and its potential metabolites.
In the search for new metyrapone derivatives as radioligands for the functional diagnosis of adrenal pathology, 2-methoxyphenylmetyrapone [2-MPMP, 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone] (1), and related 2-substituted phenylmetyrapone derivatives, have been separated as potent inhibitors of adrenal 11 beta-hydroxylase, with high affinity for adrenal mitochondrial binding sites. Surprisingly, 2-[11C]MPMP showed a rapid loss of the radioactive label, which prompted investigation of its metabolism. Synthetic 2-MPMP (1) and its seven potential metabolites (2-8) have been identified spectroscopically (1H- and 13C-NMR and mass spectrometry) and further characterised by chromatography (TLC and gradient reversed-phase HPLC). Chromatographic and mass analysis of urinary extracts from rats dosed with 2-MPMP have confirmed the major metabolites as 2-hydroxyphenylmetyrapone (2-OHPMP), 2) and its N-oxide (2-OHPMP-NO, 6), which are present predominantly as conjugates.
Ho
Y P
YP
Department of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Lin
G
G
Damani
L A
LA
Mitterhauser
M
M
Zolle
I
I
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008797:Metyrapone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley
C102846:2-methoxyphenylmetyrapone; D011849:Radioactive Tracers; D008797:Metyrapone