N-dealkylation of oxprenolol: formation of 3-aryloxypropane-1,2-diol, 3-aryloxylactic acid, and 2-aryloxyacetic acid metabolites in the rat.
Oxprenolol (1), like related beta-adrenergic antagonists, undergoes oxidative N-dealkylation to form the corresponding 3-aryloxypropane-1,2-diol (2), 3-aryloxylactic acid (3), and 2-aryloxyacetic acid (4) metabolites. Compounds 3 and 4 were synthesized by conversion of 2-allyloxyphenol (5) to the aryloxyacetaldehyde 6 and subsequent elaboration to the desired acids. Both acids (3 and 4) and glycol 2 were confirmed as metabolites formed from 1 in vivo in the rat and in vitro in the rat liver 9000 X g supernatant fraction. Incubation of a pseudoracemate of 1, made up of equal molar amounts of (2S)-1-d0 and (2R)-1-d2, showed that 2 and 3 arise principally from (2S)-1 by S/R ratios of approximately 5:1 and 2:1, respectively. On the other hand, acetic acid derivative 4 arises about equally from both enantiomers of 1.
D000818:Animals; D001711:Biotransformation; D003640:Dealkylation; D008401:Gas Chromatography-Mass Spectrometry; D006016:Glycolates / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D010096:Oxprenolol / Q000378:metabolism*; D010642:Phenoxyacetates / Q000378:metabolism*; D011409:Propylene Glycols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006016:Glycolates; D010642:Phenoxyacetates; D011409:Propylene Glycols; D010096:Oxprenolol