Metabolic pathways of the contragestational agent, 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL 111-IT), in the rat.

The metabolic pathways of the non-hormonal anti-fertility agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL 111-IT) were studied in rats given the 14C-labelled compound intramuscularly. The diaryltriazole, once absorbed, was metabolized rapidly by three phase I reactions: (a) hydroxylation at the C-4 of the methoxyphenyl ring, (b) hydroxylation at the alpha-C of the ethyl chain, and (c) demethylation of the methoxyl function. Seven free metabolites and three conjugates have been isolated and characterized by u.v., i.r., n.m.r. and mass spectroscopy. The products of the first step of metabolism of the diaryltriazole were tested for their pregnancy-terminating activity in the rat. They were only 5-9% as effective as the parent compound, indicating that the unchanged drug is the active molecule.